Marshall Protocol Knowledge Base - home:pathogenesis

Incidence and prevalence of chronic disease

anonymous@undisclosed.example.com (Anonymous) — Wed, 14 Sep 2022 20:53:47 +0000

Evidence that chronic disease is caused by pathogens

anonymous@undisclosed.example.com (Anonymous) — Wed, 14 Sep 2022 20:53:47 +0000

Evolutionary perspective on chronic disease

anonymous@undisclosed.example.com (Anonymous) — Wed, 14 Sep 2022 20:53:47 +0000

10.19.2018		current
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	====== Evolutionary perspective on chronic disease ======		====== Evolutionary perspective on chronic disease ======

-	One useful way to determine if a disease is caused by faulty human genes is look towards the central principle of evolutionary biology: evolutionary fitness. [[http://en.wikipedia.org/wiki/Fitness_(biology)\|Evolutionary fitness]] is defined as the extent to which an organism is adapted to or able to produce offspring in a particular environment. The fitness concept can be applied to the problem of disease causation to distinguish evolutionarily feasible hypotheses of causation from marginally feasible or untenable ones.(({{pubmed>long:10893730}})) (({{pubmed>long:10839723}}))	+	One useful way to determine if a disease is caused by faulty human genes is look towards the central principle of evolutionary biology: evolutionary fitness. [[https://en.wikipedia.org/wiki/Fitness_(biology)\|Evolutionary fitness]] is defined as the extent to which an organism is adapted to or able to produce offspring in a particular environment. The fitness concept can be applied to the problem of disease causation to distinguish evolutionarily feasible hypotheses of causation from marginally feasible or untenable ones.(({{pmid>long:10893730}})) (({{pmid>long:10839723}}))

	Generally speaking, diseases have three major causes: genetic, environmental, and infectious. Each disease affects, to some degree, an organism's ability to reproduce, that is, their reproductive fitness. As a general rule, infectious disease confers no reproductive benefit but genetic diseases do, either currently or historically.		Generally speaking, diseases have three major causes: genetic, environmental, and infectious. Each disease affects, to some degree, an organism's ability to reproduce, that is, their reproductive fitness. As a general rule, infectious disease confers no reproductive benefit but genetic diseases do, either currently or historically.
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	===== Genetic diseases confer a benefit =====		===== Genetic diseases confer a benefit =====

-	Major diseases known to be genetic in origin offer some characteristic which confers a reproductive edge, and almost always that edge involves resistance to infection.(({{pubmed>long:10893730}})) When a group of people having that trait migrates and that advantage is lost or starts being harmful, the gene is weeded out of the population.	+	Major diseases known to be genetic in origin offer some characteristic which confers a reproductive edge, and almost always that edge involves resistance to infection.(({{pmid>long:10893730}})) When a group of people having that trait migrates and that advantage is lost or starts being harmful, the gene is weeded out of the population.
	==== Sickle-cell anemia ====		==== Sickle-cell anemia ====

-	Although [[http://en.wikipedia.org/wiki/Cystic_fibrosis\|cystic fibrosis]], [[http://en.wikipedia.org/wiki/Thalassemia\|thalassemias]], and [[http://en.wikipedia.org/wiki/Polycystic_kidney_disease\|polycystic kidney disease]] are genetic disorders all known to prevent genetic damage caused by infection, the genetic disorder sickle-cell anemia is a [[http://en.wikipedia.org/wiki/Malaria#Evolutionary_pressure_of_malaria_on_human_genes\|prototypical example]]. In sickle-cell disease, there is a mutation in the HBB gene which confers resistance to malaria, providing a benefit in some regions of the world but doing harm in others. Groups of people who move from areas of the world infested with malaria to areas which are not, quickly lose the trait for sickle-cell within generations:	+	Although [[https://en.wikipedia.org/wiki/Cystic_fibrosis\|cystic fibrosis]], [[https://en.wikipedia.org/wiki/Thalassemia\|thalassemias]], and [[https://en.wikipedia.org/wiki/Polycystic_kidney_disease\|polycystic kidney disease]] are genetic disorders all known to prevent genetic damage caused by infection, the genetic disorder sickle-cell anemia is a [[https://en.wikipedia.org/wiki/Malaria#Evolutionary_pressure_of_malaria_on_human_genes\|prototypical example]]. In sickle-cell disease, there is a mutation in the HBB gene which confers resistance to malaria, providing a benefit in some regions of the world but doing harm in others. Groups of people who move from areas of the world infested with malaria to areas which are not, quickly lose the trait for sickle-cell within generations:

	<blockquote>Recorded history spans about 5,000 years, and the frequencies of deleterious alleles can change substantially in a small fraction of that time. Consider the sickle-cell allele [one of many competing versions of a gene], which protects heterozygotes from malaria and causes a lethal anemia in homozygotes. If a population with a sickle-cell allele frequency of 20 percent were transferred to an environment without malaria, the negative effects of sickle-cell anemia should cause the frequency of the sickle-cell allele to decrease by a factor of about three within about 10 generations. This estimate accords with geographic differences. In the United States, the sickle-cell allele frequency is about half of what would be expected from African source populations after accounting for admixture [the act of mixing or mingling]. A geographic comparison within the Caribbean between malaria-free and malaria-endemic areas is also consistent: the frequency of the sickle-cell allele is low in Curaçao, where malaria has not been endemic, but not in Surinam, where malaria has been endemic.((Vogel, F., and A. G. Motulsky. Human Genetics, 3rd ed. Berlin: Springer Verlag, 1997.))		<blockquote>Recorded history spans about 5,000 years, and the frequencies of deleterious alleles can change substantially in a small fraction of that time. Consider the sickle-cell allele [one of many competing versions of a gene], which protects heterozygotes from malaria and causes a lethal anemia in homozygotes. If a population with a sickle-cell allele frequency of 20 percent were transferred to an environment without malaria, the negative effects of sickle-cell anemia should cause the frequency of the sickle-cell allele to decrease by a factor of about three within about 10 generations. This estimate accords with geographic differences. In the United States, the sickle-cell allele frequency is about half of what would be expected from African source populations after accounting for admixture [the act of mixing or mingling]. A geographic comparison within the Caribbean between malaria-free and malaria-endemic areas is also consistent: the frequency of the sickle-cell allele is low in Curaçao, where malaria has not been endemic, but not in Surinam, where malaria has been endemic.((Vogel, F., and A. G. Motulsky. Human Genetics, 3rd ed. Berlin: Springer Verlag, 1997.))

-	//Gregory Cochran, et al.// (({{pubmed>long:10893730}}))	+	//Gregory Cochran, et al.// (({{pmid>long:10893730}}))
	</blockquote>		</blockquote>

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	If the common inflammatory diseases (including autoimmune diseases) were genetic, the only way they would manage not to be weeded out of the population would be if they conferred some sort of beneficial survival trait not related to the disease.		If the common inflammatory diseases (including autoimmune diseases) were genetic, the only way they would manage not to be weeded out of the population would be if they conferred some sort of beneficial survival trait not related to the disease.

-	To date, no such benefits have been identified in any disease, schizophrenia being a good example.(({{pubmed>long:12878806}})) Schizophrenics have a high suicide rate, few children, and a high rate of abnormality in their children.(({{pubmed>long:10978869}})) (({{pubmed>long:8885043}})) Schizophrenic mothers are more likely than non-schizophrenics to have stillborn babies and children with congenital malformations.(({{pubmed>long:11448375}}))	+	To date, no such benefits have been identified in any disease, schizophrenia being a good example.(({{pmid>long:12878806}})) Schizophrenics have a high suicide rate, few children, and a high rate of abnormality in their children.(({{pmid>long:10978869}})) (({{pmid>long:8885043}})) Schizophrenic mothers are more likely than non-schizophrenics to have stillborn babies and children with congenital malformations.(({{pmid>long:11448375}}))

	Among chronic diseases, as opposed to genetic illnesses, there has certainly been no documented increased resistance to infection. Crohn's disease is typical in that patients who suffer from the disease are known for getting [[home:diseases#evidence_of_infectious_cause\|substantially more co-infections]].		Among chronic diseases, as opposed to genetic illnesses, there has certainly been no documented increased resistance to infection. Crohn's disease is typical in that patients who suffer from the disease are known for getting [[home:diseases#evidence_of_infectious_cause\|substantially more co-infections]].
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	<blockquote>Therefore, I argue that the biological function of humans is basically over with at 20–25 years, and that is what nature is used to as well.		<blockquote>Therefore, I argue that the biological function of humans is basically over with at 20–25 years, and that is what nature is used to as well.

-	//Rolf Zinkernagel// (({{pubmed>long:18311378}}))</blockquote>	+	//Rolf Zinkernagel// (({{pmid>long:18311378}}))</blockquote>

	The problem with this argument is that many chronic diseases do strike before reproductive age. Consider, once again, schizophrenia, a disease which is not at all unique in this regard. Schizophrenia drastically reduces reproductive fitness. Epidemiological data clearly show that people with schizophrenia are much more likely die before reproductive age.		The problem with this argument is that many chronic diseases do strike before reproductive age. Consider, once again, schizophrenia, a disease which is not at all unique in this regard. Schizophrenia drastically reduces reproductive fitness. Epidemiological data clearly show that people with schizophrenia are much more likely die before reproductive age.
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	===== Persistence of chronic diseases =====		===== Persistence of chronic diseases =====

-	Further evidence against the genetic hypothesis for inflammatory disease is that a number of diseases - diseases like Crohn's, atherosclerosis, autism, breast cancer, schizophrenia and multiple sclerosis - tend to strike around or before reproductive age. These are diseases which have been around for at least thousands of years, allowing for plenty of time for harmful traits to be weeded out of the population. Manifestations of both arteriosclerosis(({{pubmed>long:10495769}})) ((Ackerknecht, E. H. (1955). //A Short History of Medicine//. New York: Ronald Press)) and cardiac disease(({{pubmed>long:10938170}})) can be observed in mummies of ancient Egypt. [[http://en.wikipedia.org/wiki/Ötzi_the_Iceman\|Ötzi the Neolithic Iceman]] who lived around 3300 BC was found to have arthritis.(({{pubmed>long:12701332}})) There is currently no evidence that any of the supposedly genetic chronic diseases haven't been around for at least millenia.	+	Further evidence against the genetic hypothesis for inflammatory disease is that a number of diseases - diseases like Crohn's, atherosclerosis, autism, breast cancer, schizophrenia and multiple sclerosis - tend to strike around or before reproductive age. These are diseases which have been around for at least thousands of years, allowing for plenty of time for harmful traits to be weeded out of the population. Manifestations of both arteriosclerosis(({{pmid>long:10495769}})) ((Ackerknecht, E. H. (1955). //A Short History of Medicine//. New York: Ronald Press)) and cardiac disease(({{pmid>long:10938170}})) can be observed in mummies of ancient Egypt. [[https://en.wikipedia.org/wiki/Ötzi_the_Iceman\|Ötzi the Neolithic Iceman]] who lived around 3300 BC was found to have arthritis.(({{pmid>long:12701332}})) There is currently no evidence that any of the supposedly genetic chronic diseases haven't been around for at least millenia.

	===== Interplay between environmental factors and genes =====		===== Interplay between environmental factors and genes =====
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	===== Read more =====		===== Read more =====

-	* [[http://bacteriality.com/2008/02/11/ewald/\|Interview with evolutionary biologist Paul Ewald]] <html> </html> [[http://bacteriality.com\|{{:home:bacteriality.gif}}]]	+	* [[https://bacteriality.com/2008/02/11/ewald/\|Interview with evolutionary biologist Paul Ewald]] <html> </html> [[https://bacteriality.com\|{{:home:bacteriality.gif}}]]
-	* [[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2841832/?tool=pubmed/\|Article by Paul Ewald on chronic diseases and immunopathology]]	+	* [[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2841832/?tool=pubmed/\|Article by Paul Ewald on chronic diseases and immunopathology]]

	{{tag> Pathogenesis}}		{{tag> Pathogenesis}}
		+	<nodisp>
	===== Notes and comments =====		===== Notes and comments =====

-	broken link --- //Sallie Q 08.21.2017// http://vetmed.illinois.edu/courses/path516/Cochran%20et%20al%5b1%5d.pdf\|Infectious causation of disease: an evolutionary persepctive	+	broken link --- https://vetmed.illinois.edu/courses/path516/Cochran%20et%20al%5b1%5d.pdf\|Infectious causation of disease: an evolutionary persepctive

	* Legacy content		* Legacy content
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-	===== References =====	+	===== References =====</nodisp>

Familial aggregation

anonymous@undisclosed.example.com (Anonymous) — Wed, 14 Sep 2022 20:53:47 +0000

Horizontal gene transfer

anonymous@undisclosed.example.com (Anonymous) — Wed, 14 Sep 2022 20:53:47 +0000

Innate immune response and Th1 inflammation

anonymous@undisclosed.example.com (Anonymous) — Wed, 14 Sep 2022 20:53:47 +0000

Koch's postulates

anonymous@undisclosed.example.com (Anonymous) — Wed, 14 Sep 2022 20:53:47 +0000

08.28.2012		current
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	According to T.D. Brock at the American Society of Microbiology,((Brock TD. (1999). //Robert Koch: a life in medicine and bacteriology//. American Society of Microbiology Press, Washington)) attempts to rigidly apply Koch’s postulates to the diagnosis of viral diseases may have significantly impeded the early development of the field of virology. It also impeded the understanding of chronic disease.		According to T.D. Brock at the American Society of Microbiology,((Brock TD. (1999). //Robert Koch: a life in medicine and bacteriology//. American Society of Microbiology Press, Washington)) attempts to rigidly apply Koch’s postulates to the diagnosis of viral diseases may have significantly impeded the early development of the field of virology. It also impeded the understanding of chronic disease.

-	In 1932, Razumov noted a large discrepancy between the viable plate count and total direct microscopic count of bacteria taken from aquatic habitats,(({{pubmed>long:18502944}})) yet his work was dismissed, underestimate, or both – undoubtedly because it was not consistent with Koch's postulates.	+	In 1932, Razumov noted a large discrepancy between the viable plate count and total direct microscopic count of bacteria taken from aquatic habitats,(({{pmid>long:18502944}})) yet his work was dismissed, underestimate, or both – undoubtedly because it was not consistent with Koch's postulates.

	The faithful adherence to Koch's ideas about disease has led researchers to overestimate their comprehension of how pathogens cause disease.		The faithful adherence to Koch's ideas about disease has led researchers to overestimate their comprehension of how pathogens cause disease.
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	For most of the twentieth century, the predominant feeling about the treatment, control and prevention of infectious diseases was optimism.		For most of the twentieth century, the predominant feeling about the treatment, control and prevention of infectious diseases was optimism.

-	//Mitchell L. Cohen// (({{pubmed>long:10963605}}))	+	//Mitchell L. Cohen// (({{pmid>long:10963605}}))
	</blockquote>		</blockquote>

	In 1931, Henry Sigerist wrote, "Most of the infectious diseases ... have now yielded up their secrets.... Many illnesses ... had been completely exterminated; others had [been brought] largely under control...."((Sigerist, H. E. //The Great Doctors 372// (Dover Publications, New York, 1971).)) Between 1940 and 1960, the development and successes of antibiotics and immunizations added to this optimism, and in 1969, Surgeon General William H. Stewart told the United States Congress that it was time to "close the book on infectious diseases."((Garrett, L. In: //AIDS in the World// (eds Mann, J. M., Tarantola, D. J. M. & Netter, T. W.) 825–839 (Harvard Univ. Press, Cambridge, Massachusetts, 1992).))		In 1931, Henry Sigerist wrote, "Most of the infectious diseases ... have now yielded up their secrets.... Many illnesses ... had been completely exterminated; others had [been brought] largely under control...."((Sigerist, H. E. //The Great Doctors 372// (Dover Publications, New York, 1971).)) Between 1940 and 1960, the development and successes of antibiotics and immunizations added to this optimism, and in 1969, Surgeon General William H. Stewart told the United States Congress that it was time to "close the book on infectious diseases."((Garrett, L. In: //AIDS in the World// (eds Mann, J. M., Tarantola, D. J. M. & Netter, T. W.) 825–839 (Harvard Univ. Press, Cambridge, Massachusetts, 1992).))

-	<html><!-- Source: http://www.nature.com/nature/journal/v406/n6797/full/406762a0.html --></html>	+	<html><!-- Source: https://www.nature.com/nature/journal/v406/n6797/full/406762a0.html --></html>

-	With "victory" declared, increasing emphasis was directed at the "non-infectious" diseases such as cancer and heart disease. Often, research on infectious disease or activities on their prevention and control were de-emphasized and resources were reduced or eliminated. As recently as the 1980s, pharmaceutical companies, believing that there were already enough antibiotics, began reducing the development of new drugs or redirecting it away from antibiotics.(({{pubmed>long:8153617}})) (({{pubmed>long:8994797}}))	+	With "victory" declared, increasing emphasis was directed at the "non-infectious" diseases such as cancer and heart disease. Often, research on infectious disease or activities on their prevention and control were de-emphasized and resources were reduced or eliminated. As recently as the 1980s, pharmaceutical companies, believing that there were already enough antibiotics, began reducing the development of new drugs or redirecting it away from antibiotics.(({{pmid>long:8153617}})) (({{pmid>long:8994797}}))


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	<blockquote>When someone talks about imbalance of humors of the miasmic origin of disease, I always detect among listeners the amused tolerance a parent gives to an explanation from his 3-yr-old son. A discourse on Koch’s postulates, on the other hand, is treated with great solemnity. In this light, my premise that there is no more dangerous half-truth among students of disease today than the postulates of Koch may be considered sacrilegious.		<blockquote>When someone talks about imbalance of humors of the miasmic origin of disease, I always detect among listeners the amused tolerance a parent gives to an explanation from his 3-yr-old son. A discourse on Koch’s postulates, on the other hand, is treated with great solemnity. In this light, my premise that there is no more dangerous half-truth among students of disease today than the postulates of Koch may be considered sacrilegious.

-	//Robert P. Hanson// (({{pubmed>long:3286904}}))</blockquote>	+	//Robert P. Hanson// (({{pmid>long:3286904}}))</blockquote>


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	<blockquote>Life has changed since the 1880s when Robert Koch elucidated his guidelines, later to be called Koch’s postulates, for determining whether a microorganism is the cause of a disease. The horse-drawn buggy bumping over dirt roads has been replaced by the computer-assisted automobile speeding along paved highways. It would be absurd to expect modern cars to abide by trafﬁc rules and standards designed for horse-drawn carriages. Yet, many continue to hold Koch’s postulates as the unchanging standard for determining causation in medicine, despite a revolution in biotechnology and leaps in medical knowledge. Recent ﬁndings based on the application of new technologies, especially in the ﬁelds of microbiology and infectious disease, demand a renewed dialogue on proof of causation and revised guidelines for deﬁning a causal relationship between a microbe and a disease.		<blockquote>Life has changed since the 1880s when Robert Koch elucidated his guidelines, later to be called Koch’s postulates, for determining whether a microorganism is the cause of a disease. The horse-drawn buggy bumping over dirt roads has been replaced by the computer-assisted automobile speeding along paved highways. It would be absurd to expect modern cars to abide by trafﬁc rules and standards designed for horse-drawn carriages. Yet, many continue to hold Koch’s postulates as the unchanging standard for determining causation in medicine, despite a revolution in biotechnology and leaps in medical knowledge. Recent ﬁndings based on the application of new technologies, especially in the ﬁelds of microbiology and infectious disease, demand a renewed dialogue on proof of causation and revised guidelines for deﬁning a causal relationship between a microbe and a disease.

-	//David N. Fredricks and David A. Relman//(({{pubmed>long:8665474}}))	+	//David N. Fredricks and David A. Relman//(({{pmid>long:8665474}}))
	</blockquote>		</blockquote>

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	The blind adherence to Koch's postulates precludes a more nuanced understanding of disease: it is in fact a group of genetically indistinct organisms, a [[home:pathogenesis:microbiota\|metagenomic microbiota]], which may cause and drive chronic disease.		The blind adherence to Koch's postulates precludes a more nuanced understanding of disease: it is in fact a group of genetically indistinct organisms, a [[home:pathogenesis:microbiota\|metagenomic microbiota]], which may cause and drive chronic disease.

-	In a 2005 //Lancet// paper, Brogden //et al.// point to the existence of dozens of polymicrobial diseases, caused by combinations of viruses, bacteria, fungi, and parasites.(({{pubmed>long:15652608}})) In these infections, the presence of one micro-organism generates a niche for other pathogenic micro-organisms to colonise, one micro-organism predisposes the host to colonisation by other micro-organisms, or two or more non-pathogenic micro-organisms together cause disease.	+	In a 2005 //Lancet// paper, Brogden //et al.// point to the existence of dozens of polymicrobial diseases, caused by combinations of viruses, bacteria, fungi, and parasites.(({{pmid>long:15652608}})) In these infections, the presence of one micro-organism generates a niche for other pathogenic micro-organisms to colonise, one micro-organism predisposes the host to colonisation by other micro-organisms, or two or more non-pathogenic micro-organisms together cause disease. This topic is discussed further in the article [[home:pathogenesis:successive_infection\|Successive infection and variability in disease]].


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	{{tag> Pathogenesis Study_Design}}		{{tag> Pathogenesis Study_Design}}
		+	<nodisp>
	===== Notes and comments =====		===== Notes and comments =====

	* Legacy content		* Legacy content
-	* http://bacteriality.com/2007/08/28/horizontal-gene-transfer/	+	* https://bacteriality.com/2007/08/28/horizontal-gene-transfer/


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	L. Garrett. 2000. Betrayal of Trust: The Collapse of Global Public Health. New York. Hyperion: 474.		L. Garrett. 2000. Betrayal of Trust: The Collapse of Global Public Health. New York. Hyperion: 474.

-	B. Gewen. ‘The Great Influenza’ and ‘Microbial Threats to Health’: Virus Alert. The New York Times March 14, 2004, available at: http://www.nytimes.com/ 2004/03/14/books/review/14GEWENT.html.	+	B. Gewen. ‘The Great Influenza’ and ‘Microbial Threats to Health’: Virus Alert. The New York Times March 14, 2004, available at: https://www.nytimes.com/ 2004/03/14/books/review/14GEWENT.html.
		+
		+	===== References =====</nodisp>

-	===== References =====

Microbes in the human body

anonymous@undisclosed.example.com (Anonymous) — Wed, 14 Sep 2022 20:53:47 +0000

Successive infection and variability in disease

anonymous@undisclosed.example.com (Anonymous) — Wed, 14 Sep 2022 20:53:47 +0000

Th1 Spectrum Disorder

anonymous@undisclosed.example.com (Anonymous) — Tue, 26 Aug 2025 10:17:57 +0000

01.13.2024		current
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-
	====== Th1 Spectrum Disorder ======		====== Th1 Spectrum Disorder ======

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	Epidemiological research may have its share of liabilities, but one contribution it has made is in demonstrating the strong connections between seemingly disparate diseases as evidenced by the number of patients who share diagnoses with two or more "unrelated" disease processes.		Epidemiological research may have its share of liabilities, but one contribution it has made is in demonstrating the strong connections between seemingly disparate diseases as evidenced by the number of patients who share diagnoses with two or more "unrelated" disease processes.

-	<nodisp>
	The following wheel shows how truly related chronic diseases are. Each "spoke" represents a published study which has demonstrated a significant statistical relationship between patients suffering from one disease and the next.		The following wheel shows how truly related chronic diseases are. Each "spoke" represents a published study which has demonstrated a significant statistical relationship between patients suffering from one disease and the next.

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	</html>		</html>
	The following paragraph contains links to all the studies alluded to in the above chart.		The following paragraph contains links to all the studies alluded to in the above chart.
-	</nodisp>

	Please note that some of the disease names in the following paragraph are links to articles discussing those diseases in further detail.		Please note that some of the disease names in the following paragraph are links to articles discussing those diseases in further detail.

Transmission of bacteria and onset of chronic disease

anonymous@undisclosed.example.com (Anonymous) — Wed, 14 Sep 2022 20:53:47 +0000

Science behind vitamin D

anonymous@undisclosed.example.com (Anonymous) — Sun, 06 Aug 2023 22:15:03 +0000

09.14.2022		current
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	==== Failing to control for biases inherent to observational studies ====		==== Failing to control for biases inherent to observational studies ====

-	<mainrelatedarticles> [[.:vitamind:observational_bias\|Bias in observational epidemiological studies]], [[home:pathogenesis:vitamind:latitude\|Latitude studies]]</article>	+	<mainarticle> [[.:vitamind:observational_bias\|Bias in observational epidemiological studies]], [[home:pathogenesis:vitamind:latitude\|Latitude studies]]</article>

	{{section>:home:pathogenesis:vitamind:observational_bias#bias_in_observational_epidemiological_studies&noheader}}		{{section>:home:pathogenesis:vitamind:observational_bias#bias_in_observational_epidemiological_studies&noheader}}

01.03.2012		current
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	[{{ :home:pathogenesis:04f1.jpg?450\|A multi-generational map showing familial aggregation of Parkinson's disease in a large Icelandic family. Patients with Parkinson's are solid symbols. Those with asterisks indicate patients with early-onset Parkinson's disease. Slash marks denote family members listed in a local death registry. Source: Sveinbjörnsdóttir.}}]		[{{ :home:pathogenesis:04f1.jpg?450\|A multi-generational map showing familial aggregation of Parkinson's disease in a large Icelandic family. Patients with Parkinson's are solid symbols. Those with asterisks indicate patients with early-onset Parkinson's disease. Slash marks denote family members listed in a local death registry. Source: Sveinbjörnsdóttir.}}]

-	* sarcoidosis – A six-year study of the Th1 disease sarcoidosis, conducted by the National Heart, Lung and Blood Institute at the National Institutes of Health (NIH) in Maryland found that among the 215 study participants who had been diagnosed with sarcoidosis, there were five husband-and-wife couples that both had the disease. Yet sarcoidosis is such a rare disease that, statistically speaking, there should have been none. This means the incidence of sarcoidosis in spouses in the study was 1,000 greater than could be expected by chance. The researchers also noted that the risk for sarcoidosis increased nearly five-fold in parents and siblings of people with the disease. (({{pubmed>long:17684288}}))	+	* sarcoidosis – A six-year study of the Th1 disease sarcoidosis, conducted by the National Heart, Lung and Blood Institute at the National Institutes of Health (NIH) in Maryland found that among the 215 study participants who had been diagnosed with sarcoidosis, there were five husband-and-wife couples that both had the disease. Yet sarcoidosis is such a rare disease that, statistically speaking, there should have been none. This means the incidence of sarcoidosis in spouses in the study was 1,000 greater than could be expected by chance. The researchers also noted that the risk for sarcoidosis increased nearly five-fold in parents and siblings of people with the disease. (({{pmid>long:17684288}}))
-	* hypertension – Researchers at Queens Medical School in England found that men whose spouses had hypertension had a two-fold increased risk of hypertension. Similarly, women whose spouses had hypertension also doubled their risk of developing the disease. The risk for both male and female subjects persisted after adjustment for other variables such as diet. (({{pubmed>long:9830183}}))	+	* hypertension – Researchers at Queens Medical School in England found that men whose spouses had hypertension had a two-fold increased risk of hypertension. Similarly, women whose spouses had hypertension also doubled their risk of developing the disease. The risk for both male and female subjects persisted after adjustment for other variables such as diet. (({{pmid>long:9830183}}))
-	* exfoliative glaucoma – In the middle Norway eye-screening study, the prevalence of XFG in both members of married couples is significantly higher than expected, "thereby suggesting a common environmental (probably infectious) agent, which may be of aetiological significance for the XFG development."(({{pubmed>long:19854735}}))	+	* exfoliative glaucoma – In the middle Norway eye-screening study, the prevalence of XFG in both members of married couples is significantly higher than expected, "thereby suggesting a common environmental (probably infectious) agent, which may be of aetiological significance for the XFG development."(({{pmid>long:19854735}}))


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	Family members are much more likely to have a disease when a family member has the disease. This is especially true of diseases between mother and child: chronic diseases are often said to "pass down the maternal line."		Family members are much more likely to have a disease when a family member has the disease. This is especially true of diseases between mother and child: chronic diseases are often said to "pass down the maternal line."

-	* autoimmune disease – A 2007 Danish study looked at the lifetime prevalence of 31 "autoimmune" diseases in 5.5 million people, the entire population of Denmark. According to the study's authors, there was "considerable familial aggregation in almost all 31 diseases." In other words, if you have a sibling or parent with a disease, you are much more likely to have that disease yourself, in some cases more than one hundred times more likely. There were only three diseases for which there may have been some doubt and even those met the threshold of statistical significance.(({{pubmed>long:17582741}}))	+	* autoimmune disease – A 2007 Danish study looked at the lifetime prevalence of 31 "autoimmune" diseases in 5.5 million people, the entire population of Denmark. According to the study's authors, there was "considerable familial aggregation in almost all 31 diseases." In other words, if you have a sibling or parent with a disease, you are much more likely to have that disease yourself, in some cases more than one hundred times more likely. There were only three diseases for which there may have been some doubt and even those met the threshold of statistical significance.(({{pmid>long:17582741}}))
	* chronic fatigue syndrome – Dr. Garth Nicholson, a researcher at The Institute of Molecular Medicine in California has also conducted several studies on the communicability of diseases such as chronic fatigue syndrome, autism and Gulf War Syndrome (a disease with symptoms very similar to those of CFS). He noted that among soldiers who developed Gulf War Syndrome during the war in Iraq, 70% or more of family members showed symptoms of the same disease within 10 years after the soldier had returned from the war. At the 2006 Autoimmunity Research Foundation Conference in Chicago, British clinician and Chronic Fatigue Syndrome researcher Dr. Andy Wright stated that he very rarely sees a family in which the spouses do not both have the Th1 pathogens in their blood.		* chronic fatigue syndrome – Dr. Garth Nicholson, a researcher at The Institute of Molecular Medicine in California has also conducted several studies on the communicability of diseases such as chronic fatigue syndrome, autism and Gulf War Syndrome (a disease with symptoms very similar to those of CFS). He noted that among soldiers who developed Gulf War Syndrome during the war in Iraq, 70% or more of family members showed symptoms of the same disease within 10 years after the soldier had returned from the war. At the 2006 Autoimmunity Research Foundation Conference in Chicago, British clinician and Chronic Fatigue Syndrome researcher Dr. Andy Wright stated that he very rarely sees a family in which the spouses do not both have the Th1 pathogens in their blood.
-	* autism – Scientists at the University of Maastricht in the Netherlands also found that relatives of individuals with autism often begin to show mild autistic traits, a phenomenon known as the broader autism phenotype (BAP). In one study conducted by the group, fathers with an autistic child demonstrated a different reaction time pattern and responded slower on the social cues than control fathers.(({{pubmed>long:17588199}}))	+	* autism – Scientists at the University of Maastricht in the Netherlands also found that relatives of individuals with autism often begin to show mild autistic traits, a phenomenon known as the broader autism phenotype (BAP). In one study conducted by the group, fathers with an autistic child demonstrated a different reaction time pattern and responded slower on the social cues than control fathers.(({{pmid>long:17588199}}))
-	* Alzheimer's Disease – A 2010 //NYU// study using a PET scanner to examine the plaque in brains (which is the hallmark of Alzheimer's disease) found that a child's level of plaque was consistent with their fathers and especially their mothers – even years before a child had a diagnosis.(({{pubmed>long:20231448}})) The fact that amyloid-beta protein has recently been identified as an antimicrobial peptide(({{pubmed>long:20209079}})) suggests that what is being passed between the generations isn't so much the propensity to produce plaque, but the need to produce plaque in response to brain infection.	+	* Alzheimer's Disease – A 2010 //NYU// study using a PET scanner to examine the plaque in brains (which is the hallmark of Alzheimer's disease) found that a child's level of plaque was consistent with their fathers and especially their mothers – even years before a child had a diagnosis.(({{pmid>long:20231448}})) The fact that amyloid-beta protein has recently been identified as an antimicrobial peptide(({{pmid>long:20209079}})) suggests that what is being passed between the generations isn't so much the propensity to produce plaque, but the need to produce plaque in response to brain infection.
	[{{ :home:pathogenesis:1471-2350-9-6-1.jpg?320\|Familial aggregation of two different diseases as seen in a large Swedish/Norwegian family. The family suffers from high incidence of schizophrenia (yellow) and mental retardation (blue). No genetic cause for these epidemic levels of disease have been found. Source: Beleza-Meireles}}]		[{{ :home:pathogenesis:1471-2350-9-6-1.jpg?320\|Familial aggregation of two different diseases as seen in a large Swedish/Norwegian family. The family suffers from high incidence of schizophrenia (yellow) and mental retardation (blue). No genetic cause for these epidemic levels of disease have been found. Source: Beleza-Meireles}}]
	==== Family members are more likely to develop different diseases too ====		==== Family members are more likely to develop different diseases too ====
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	It should be noted that none of the above studies take into consideration the fact that spouses and siblings very often develop different forms of chronic disease. If researchers were to look for the incidence of Th1 disease among family members and take into account all possible inflammatory diagnoses, all of the above numbers would be notably higher.		It should be noted that none of the above studies take into consideration the fact that spouses and siblings very often develop different forms of chronic disease. If researchers were to look for the incidence of Th1 disease among family members and take into account all possible inflammatory diagnoses, all of the above numbers would be notably higher.

-	* mental disorders – A 2008 study of parents of children with autism found they were more likely to have been hospitalized for a mental disorder than parents of control subjects. Schizophrenia was more common among case mothers and fathers compared with respective control parents.(({{pubmed>long:18450879}})) In a case study, Beleza-Meirles found that schizophrenia and mental retardation had very high rates of incidence in a particular family.(({{pubmed>long:18254962}})) A similar by Sveinbjörnsdóttir also observed high rates of Parkinson's in an extended family.(({{pubmed>long:11114315}}))	+	* mental disorders – A 2008 study of parents of children with autism found they were more likely to have been hospitalized for a mental disorder than parents of control subjects. Schizophrenia was more common among case mothers and fathers compared with respective control parents.(({{pmid>long:18450879}})) In a case study, Beleza-Meirles found that schizophrenia and mental retardation had very high rates of incidence in a particular family.(({{pmid>long:18254962}})) A similar by Sveinbjörnsdóttir also observed high rates of Parkinson's in an extended family.(({{pmid>long:11114315}}))
-	* autism and eye disorders – Researchers working at the University of Illinois at Chicago have found a [[http://www.scientificamerican.com/article.cfm?id=autism-relatives-symptoms\|striking trend]]: those with autistic relatives are more likely to show disrupted eye movement similar to their afflicted relation.(({{pubmed>long:20679591}}))	+	* autism and eye disorders – Researchers working at the University of Illinois at Chicago have found a [[https://www.scientificamerican.com/article.cfm?id=autism-relatives-symptoms\|striking trend]]: those with autistic relatives are more likely to show disrupted eye movement similar to their afflicted relation.(({{pmid>long:20679591}}))
		+	* autoimmune disease – In a study of families who have a member with primary Sjögren's syndrome, 38% had at least one first-degree relative with an autoimmune disease, versus 22% in control families.(({{pmid>long:17086607}})) The most frequent autoimmune diseases registered among the patients' first-degree relatives were autoimmune thyroid disease, systemic lupus erythematosus, and rheumatoid arthritis.

	As evidenced by progress reports on the Marshall Protocol site, there are a substantial number of spouses who both suffer from chronic inflammatory diseases. There are also entire families on the MP - with each member using the treatment to eliminate his or her own [[home:pathogenesis:successive_infection#pea_soup\|pea-soup]].		As evidenced by progress reports on the Marshall Protocol site, there are a substantial number of spouses who both suffer from chronic inflammatory diseases. There are also entire families on the MP - with each member using the treatment to eliminate his or her own [[home:pathogenesis:successive_infection#pea_soup\|pea-soup]].

	When one considers how often chronic diseases co-occur within a family unit – heart disease, arthritis, bipolar disorder, breast cancer, inflammatory bowel disease, Alzheimer’s disease – it becomes increasingly plausible that nearly all inflammatory diseases are communicable and that this communicability results in familial aggregation.		When one considers how often chronic diseases co-occur within a family unit – heart disease, arthritis, bipolar disorder, breast cancer, inflammatory bowel disease, Alzheimer’s disease – it becomes increasingly plausible that nearly all inflammatory diseases are communicable and that this communicability results in familial aggregation.
-
	===== Non-relations in close proximity develop the same diseases =====		===== Non-relations in close proximity develop the same diseases =====

	As would be expected for the Th1 diseases, which are [[home:pathogenesis:transmission\|transmitted via proximity and contact]], even people who are not related pass diseases to each other.		As would be expected for the Th1 diseases, which are [[home:pathogenesis:transmission\|transmitted via proximity and contact]], even people who are not related pass diseases to each other.

-	* Alzheimer's – A subject whose spouse experienced incident dementia onset had a [[http://www.wired.com/wiredscience/2010/05/dementia-caregiver-risk/\|six times greater risk]] for incident dementia as subjects whose spouses were dementia free.((Norton MC, Smith KR, Øÿstbye T, Tschanz JT, Corcoran C, Schwartz S, et al. [[http://www3.interscience.wiley.com/journal/123421692/abstract?CRETRY=1&SRETRY=0\|Greater Risk of Dementia When Spouse Has Dementia? The Cache County Study]]. //Journal of the American Geriatrics Society//. 2010;58(5):895-900.))	+	* Alzheimer's – A subject whose spouse experienced incident dementia onset had a [[https://www.wired.com/wiredscience/2010/05/dementia-caregiver-risk/\|six times greater risk]] for incident dementia as subjects whose spouses were dementia free.((Norton MC, Smith KR, Øÿstbye T, Tschanz JT, Corcoran C, Schwartz S, et al. [[https://www3.interscience.wiley.com/journal/123421692/abstract?CRETRY=1&SRETRY=0\|Greater Risk of Dementia When Spouse Has Dementia? The Cache County Study]]. //Journal of the American Geriatrics Society//. 2010;58(5):895-900.))
-	* multiple sclerosis – Multiple sclerosis occurred in epidemic form in various North Atlantic islands: probably in Iceland and the Shetland-Orkneys; clearly in the Faroe Islands. In the Faroes first symptom onset was in 1943, heralding the first of four successive epidemics at 13 year intervals. The disease was presumably introduced by occupying British troops during World War II, with the postwar occurrences representing later transmissions to and from consecutive cohorts of Faroese.(({{pubmed>long:10871801}}))	+	* multiple sclerosis – Multiple sclerosis occurred in epidemic form in various North Atlantic islands: probably in Iceland and the Shetland-Orkneys; clearly in the Faroe Islands. In the Faroes first symptom onset was in 1943, heralding the first of four successive epidemics at 13 year intervals. The disease was presumably introduced by occupying British troops during World War II, with the postwar occurrences representing later transmissions to and from consecutive cohorts of Faroese.(({{pmid>long:10871801}}))
-	* obesity – Research suggests that obesity is also an inflammatory disease caused by certain species of the Th1 pathogens. A study recently published in the New England Journal of Medicine found that a person’s risk of becoming obese increases by 57% if they have a friend who becomes obese, and by 37% if their spouse becomes obese. (({{pubmed>long:17652652}})) The researchers attributed the results to social factors, but the spread of bacteria is a more logical explanation.	+	* obesity – Research suggests that obesity is also an inflammatory disease caused by certain species of the Th1 pathogens. A study recently published in the New England Journal of Medicine found that a person’s risk of becoming obese increases by 57% if they have a friend who becomes obese, and by 37% if their spouse becomes obese. (({{pmid>long:17652652}})) The researchers attributed the results to social factors, but the spread of bacteria is a more logical explanation.
-	* Parkinson's disease – A cluster of 13 cases of Parkinson's disease among a community of 592 people were reported in Israel, significantly more that would be expected by chance.(({{pubmed>long:2334236}}))	+	* Parkinson's disease – A cluster of 13 cases of Parkinson's disease among a community of 592 people were reported in Israel, significantly more that would be expected by chance.(({{pmid>long:2334236}}))
-	* sarcoidosis – A case-controlled study of residents of the Isle of Man found that 40 percent of people with sarcoidosis had been in contact with a person known to have the disease, compared with 1 to 2 percent of the control subjects. (({{pubmed>long:16844727}})) Another study reported three cases of sarcoidosis among ten firefighters who apprenticed together. (({{pubmed>long:8214953}}))	+	* sarcoidosis – A case-controlled study of residents of the Isle of Man found that 40 percent of people with sarcoidosis had been in contact with a person known to have the disease, compared with 1 to 2 percent of the control subjects. (({{pmid>long:16844727}})) Another study reported three cases of sarcoidosis among ten firefighters who apprenticed together. (({{pmid>long:8214953}}))


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		+	<nodisp>
	===== Notes and comments =====		===== Notes and comments =====

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	*		*

-	===== References =====	+	===== References =====</nodisp>

02.13.2019		current
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	HGT often happens via plasmids, circular molecules of DNA that can replicate independently of a pathogen’s other genetic material.		HGT often happens via plasmids, circular molecules of DNA that can replicate independently of a pathogen’s other genetic material.

-	There is strong genomic evidence that bacteria often acquire evolutionary novelties from outside their ancestral population by horizontal gene transfer. Researchers at the Cancer Research Institute in Slovakia analyzed the bacterial DNA isolated from the intestinal tract of 11 American and 30 Slovak patients with HIV/AIDS. They found that the intestinal bacteria genes were more than 90% homologous to the corresponding sequence in HIV – suggesting that the bacteria and the HIV virus had traded a significant amount of genetic material.(({{pubmed>long:17984947}}))	+	There is strong genomic evidence that bacteria often acquire evolutionary novelties from outside their ancestral population by horizontal gene transfer. Researchers at the Cancer Research Institute in Slovakia analyzed the bacterial DNA isolated from the intestinal tract of 11 American and 30 Slovak patients with HIV/AIDS. They found that the intestinal bacteria genes were more than 90% homologous to the corresponding sequence in HIV – suggesting that the bacteria and the HIV virus had traded a significant amount of genetic material.(({{pmid>long:17984947}}))

	The following microbes have been documented to evolve, through horizontal gene transfer, certain key evolutionary advantages:		The following microbes have been documented to evolve, through horizontal gene transfer, certain key evolutionary advantages:
-	* //Staphylococcus aureus// – resistance to methicillin (an antibiotic) (({{pubmed>long:10348769}}))	+	* //Staphylococcus aureus// – resistance to methicillin (an antibiotic) (({{pmid>long:10348769}}))
-	* //Shigella flexneri// and others – resistance to multiple antibiotics (({{pubmed>long:11544236}}))	+	* //Shigella flexneri// and others – resistance to multiple antibiotics (({{pmid>long:11544236}}))
-	* //Escherichia coli// and others – iron uptake (({{pubmed>long:10675599}}))	+	* //Escherichia coli// and others – iron uptake (({{pmid>long:10675599}}))
-	* //Proidencia rettgeri// – resistance to kanamycin (an antibiotic) (({{pubmed>long:12193633}}))	+	* //Proidencia rettgeri// – resistance to kanamycin (an antibiotic) (({{pmid>long:12193633}}))


	===== Acquired virulence =====		===== Acquired virulence =====

-	The transfer of DNA among pathogens means that once harmless microbes can acquire properties that allow them to cause problems for the host. “The mobile nature of... gene islands, transported between bacteria via plasmids or phages, creates the potential for acquired virulence in previously innocuous microbes,” states researcher Dave Relman of Stanford University. “This concept should inspire some reflection the next time one receives a culture report reading 'normal flora.'”(({{pubmed>long:9779355}}))	+	The transfer of DNA among pathogens means that once harmless microbes can acquire properties that allow them to cause problems for the host. “The mobile nature of... gene islands, transported between bacteria via plasmids or phages, creates the potential for acquired virulence in previously innocuous microbes,” states researcher Dave Relman of Stanford University. “This concept should inspire some reflection the next time one receives a culture report reading 'normal flora.'”(({{pmid>long:9779355}}))

-	The bacterial pathogen //Vibrio cholerae// has evolved resistance to a number of antibiotics (none of which are MP antibiotics) in about 10 years' time(({{pubmed>long:14688795}})) passing on to other microbes what researchers have called islands of mobile pathogenecity.(({{pubmed>long:15100694}})) According to Beaber //et al//, when //Vibrio cholerae// is exposed to the antibiotic ciprofloxacin, it will actually promote the spread of antibiotic resistance genes.(({{pubmed>long:14688795}}))	+	The bacterial pathogen //Vibrio cholerae// has evolved resistance to a number of antibiotics (none of which are MP antibiotics) in about 10 years' time(({{pmid>long:14688795}})) passing on to other microbes what researchers have called islands of mobile pathogenecity.(({{pmid>long:15100694}})) According to Beaber //et al//, when //Vibrio cholerae// is exposed to the antibiotic ciprofloxacin, it will actually promote the spread of antibiotic resistance genes.(({{pmid>long:14688795}}))

	Also, for example, take the bacterial species //Bacillus anthracis//, a species of bacteria that has two plasmids. One plasmid codes for genes that allow the pathogens to create toxins, the other codes for proteins that help it evade the immune system by living inside the white blood cells that kill and digest bacteria.		Also, for example, take the bacterial species //Bacillus anthracis//, a species of bacteria that has two plasmids. One plasmid codes for genes that allow the pathogens to create toxins, the other codes for proteins that help it evade the immune system by living inside the white blood cells that kill and digest bacteria.
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	One study looked at several species of insects and roundworms infected by a parasitic bacterium called //Wolbachia pipientis//. The bacterium lives inside animals’ cells, including their egg cells, giving it ready access to the chromosomes that are passed on to the animals’ offspring.		One study looked at several species of insects and roundworms infected by a parasitic bacterium called //Wolbachia pipientis//. The bacterium lives inside animals’ cells, including their egg cells, giving it ready access to the chromosomes that are passed on to the animals’ offspring.

-	When the researchers compared the genetic code of the bacterium with the code of 11 other species: four roundworms, four fruit flies, and three wasps, they found that all but three of the fruit fly species had segments of the bacterium’s genetic code embedded in their DNA.(({{pubmed>long:17761848}}))	+	When the researchers compared the genetic code of the bacterium with the code of 11 other species: four roundworms, four fruit flies, and three wasps, they found that all but three of the fruit fly species had segments of the bacterium’s genetic code embedded in their DNA.(({{pmid>long:17761848}}))

	Whether this occurs in humans has not yet been demonstrated, but the bacterial mutation of human DNA is consistent with the Marshall Pathogenesis and might explain the low levels of genetic concordance among people who have the same disease.		Whether this occurs in humans has not yet been demonstrated, but the bacterial mutation of human DNA is consistent with the Marshall Pathogenesis and might explain the low levels of genetic concordance among people who have the same disease.
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	===== Read more =====		===== Read more =====

-	* [[http://bacteriality.com/2008/04/06/genetransfer/\|Insights into horizontal gene transfer: conversations with Dr. Peter Gogarten and Dr. James Lake]] <html> </html> [[http://bacteriality.com\|{{:home:bacteriality.gif}}]]	+	* [[https://bacteriality.com/2008/04/06/genetransfer/\|Insights into horizontal gene transfer: conversations with Dr. Peter Gogarten and Dr. James Lake]] <html> </html> [[https://bacteriality.com\|{{:home:bacteriality.gif}}]]
-	* [[http://bacteriality.com/2007/12/30/dnatransfer/\|Horizontal DNA transfer also causes bacterial DNA to be passed from generation to generation]] <html> </html> [[http://bacteriality.com\|{{:home:bacteriality.gif}}]]	+	* [[https://bacteriality.com/2007/12/30/dnatransfer/\|Horizontal DNA transfer also causes bacterial DNA to be passed from generation to generation]] <html> </html> [[https://bacteriality.com\|{{:home:bacteriality.gif}}]]


	{{tag> Pathogenesis}}		{{tag> Pathogenesis}}

		+	<nodisp>
	===== Notes and comments =====		===== Notes and comments =====
		+
		+	//link no longer lads to cited author//
		+	[[https://www.esalenctr.org/display/confpage.cfm?confid=10&pageid=105&pgtype=1\|described]]
		+

	* Legacy content		* Legacy content
-	* http://www.marshallprotocol.com/view_topic.php?id=2810&forum_id=2&jump_to=55165#p55165 e85	+	* https://www.marshallprotocol.com/view_topic.php?id=2810&forum_id=2&jump_to=55165#p55165 e85
	*		*

-	===== References =====	+	===== References =====</nodisp>

01.12.2020		current
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	===== Introduction =====		===== Introduction =====

-	The innate immune response is the body's first line of defense against and a non-specific way for responding to bacterial pathogens.(({{pubmed>long:19400860}})) Located in the nucleus of a variety of cells, the Vitamin D nuclear receptor (VDR)	+	The innate immune response is the body's first line of defense against and a non-specific way for responding to bacterial pathogens.(({{pmid>long:19400860}})) Located in the nucleus of a variety of cells, the Vitamin D nuclear receptor (VDR)
-	plays a crucial, often under-appreciated, role in the innate immune response. [[http://journal.frontiersin.org/article/10.3389/fimmu.2013.00148/full\|The vitamin D receptor and T cell function]]	+	plays a crucial, often under-appreciated, role in the innate immune response. [[https://journal.frontiersin.org/article/10.3389/fimmu.2013.00148/full\|The vitamin D receptor and T cell function]]

-	When functioning properly, the VDR transcribes between hundreds(({{pubmed>long:20736230}})) and thousands of genes(({{pubmed>long:16002434}})) including those for the proteins known as the antimicrobial peptides. Antimicrobial peptides are "the body's natural antibiotics," crucial for both prevention and clearance of infection.(({{pubmed>long:11807545}})) The VDR also expresses the TLR2 receptor, which is expressed on the surface of certain cells and recognizes foreign substances.	+	When functioning properly, the VDR transcribes between hundreds(({{pmid>long:20736230}})) and thousands of genes(({{pmid>long:16002434}})) including those for the proteins known as the antimicrobial peptides. Antimicrobial peptides are "the body's natural antibiotics," crucial for both prevention and clearance of infection.(({{pmid>long:11807545}})) The VDR also expresses the TLR2 receptor, which is expressed on the surface of certain cells and recognizes foreign substances.

	The body controls activity of the VDR through regulation of the vitamin D metabolites. 25-hydroxyvitamin D (25-D) antagonizes or inactivates the Receptor while 1,25-dihydroxyvitamin D (1,25-D) agonizes or activates the Receptor.		The body controls activity of the VDR through regulation of the vitamin D metabolites. 25-hydroxyvitamin D (25-D) antagonizes or inactivates the Receptor while 1,25-dihydroxyvitamin D (1,25-D) agonizes or activates the Receptor.

-	Greater than 36 types of tissue have been identified as having a Vitamin D Receptor.(({{pubmed>long:18689389}}))	+	Greater than 36 types of tissue have been identified as having a Vitamin D Receptor.(({{pmid>long:18689389}}))

	Another component of the innate immune response is the release of inflammatory cytokines. The result is what medicine calls inflammation, which generally leads to an increase in symptoms.		Another component of the innate immune response is the release of inflammatory cytokines. The result is what medicine calls inflammation, which generally leads to an increase in symptoms.

-	Adenosine: an endogenous regulator of innate immunity. (({{pubmed>long:14698282}}))	+	Adenosine: an endogenous regulator of innate immunity. (({{pmid>long:14698282}}))

	Before the Human Microbiome Project, scientists couldn't link bacteria to inflammatory diseases. But with the advent of DNA sequencing technology, scientists have detected many of the bacteria capable of generating an inflammatory response. All diseases of unknown etiology are inflammatory diseases.		Before the Human Microbiome Project, scientists couldn't link bacteria to inflammatory diseases. But with the advent of DNA sequencing technology, scientists have detected many of the bacteria capable of generating an inflammatory response. All diseases of unknown etiology are inflammatory diseases.
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	===== Research =====		===== Research =====

-	Modern vaccinations, fear of germs and obsession with hygiene are depriving the immune system of the information input upon which it is dependent. ....and may lead to increased incidences of allergies and autoimmune diseases. (({{pubmed>long:9540269}}))	+	Those with a high intellectual capacity (hyper brain) possess overexcitabilities in various domains that may predispose them to certain psychological disorders as well as physiological conditions involving elevated sensory, and altered immune and inflammatory responses (hyper body). [[https://www.sciencedirect.com/science/article/pii/S0160289616303324\|Science Direct]]
		+
		+	Modern vaccinations, fear of germs and obsession with hygiene are depriving the immune system of the information input upon which it is dependent. ....and may lead to increased incidences of allergies and autoimmune diseases. (({{pmid>long:9540269}}))

	Country kids had more, and more-diverse, bacteria on their skin, with a particularly high abundance of Acinetobacter—a genus of microbes in the Proteobacteria phylum that are commonly found on plants. The researchers further found that children with more Acinetobacter on their skin had more leukocytes in their bloodstream and that these cells were much more capable of producing the anti-inflammatory cytokine IL-10 compared with the leukocytes of urban kids. [[https://www.the-scientist.com/news-opinion/the-influence-of-soil-on-human-health-66885\|influence of soil on human health]]		Country kids had more, and more-diverse, bacteria on their skin, with a particularly high abundance of Acinetobacter—a genus of microbes in the Proteobacteria phylum that are commonly found on plants. The researchers further found that children with more Acinetobacter on their skin had more leukocytes in their bloodstream and that these cells were much more capable of producing the anti-inflammatory cytokine IL-10 compared with the leukocytes of urban kids. [[https://www.the-scientist.com/news-opinion/the-influence-of-soil-on-human-health-66885\|influence of soil on human health]]

-	Insulin gives an extra boost to the immune system (({{pubmed>long:30174303}}))	+	Insulin gives an extra boost to the immune system (({{pmid>long:30174303}}))

-	Results indicate a relationship between muscular TLR4, p-AMPK and NF-κB content and insulin sensitivity. The study also highlights that in situations of insulin resistance, such as in diabetic subjects, metformin treatment may prevent attenuation of activation of the inflammatory pathway. (({{pubmed>long:28791487}}))	+	Results indicate a relationship between muscular TLR4, p-AMPK and NF-κB content and insulin sensitivity. The study also highlights that in situations of insulin resistance, such as in diabetic subjects, metformin treatment may prevent attenuation of activation of the inflammatory pathway. (({{pmid>long:28791487}}))

-	Glucose homeostasis, nutrition and infections during critical illness (({{pubmed>long:28082192}}))	+	Glucose homeostasis, nutrition and infections during critical illness (({{pmid>long:28082192}}))

-	Adenosine is an important molecule that exerts control on the immune system, by signaling through receptors lying on the surface of immune cells. (({{pubmed>long:27557887}}))	+	Adenosine is an important molecule that exerts control on the immune system, by signaling through receptors lying on the surface of immune cells. (({{pmid>long:27557887}}))

	An exciting area of recent investigation has arisen from the discovery that SCFA play a role in regulating the immune system and inflammatory response. Early work at the turn of this century had demonstrated the potential role of butyrate in immune regulation when it was shown that butyrate inhibits nuclear factor kappa β (NF-κΒ) activation in macrophages and also inhibits histone deacetylation (HDAc) in acute myeloid leukemia.		An exciting area of recent investigation has arisen from the discovery that SCFA play a role in regulating the immune system and inflammatory response. Early work at the turn of this century had demonstrated the potential role of butyrate in immune regulation when it was shown that butyrate inhibits nuclear factor kappa β (NF-κΒ) activation in macrophages and also inhibits histone deacetylation (HDAc) in acute myeloid leukemia.
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	Whether SCFA act as a signal to induce tolerance to the host-associated microbiome or directly reduce inflammatory responses remains to be fully elucidated. SCFA do appear able to reduce the responsiveness of lamina propria macrophages to commensal bacteria, via nitric oxide, IL-6, and IL-12 independent of FFAR signaling, to induce tolerance.		Whether SCFA act as a signal to induce tolerance to the host-associated microbiome or directly reduce inflammatory responses remains to be fully elucidated. SCFA do appear able to reduce the responsiveness of lamina propria macrophages to commensal bacteria, via nitric oxide, IL-6, and IL-12 independent of FFAR signaling, to induce tolerance.

-	Recent data also suggests butyrate suppresses TNF-α, IL-6, and myeloperoxidase activity by preventing NF-κΒ activation in Kupffer cells.(({{pubmed>long:26963409}}))	+	Recent data also suggests butyrate suppresses TNF-α, IL-6, and myeloperoxidase activity by preventing NF-κΒ activation in Kupffer cells.(({{pmid>long:26963409}}))

01.12.2020		current
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	====== Microbes in the human body ======		====== Microbes in the human body ======

-	According to a recent National Institutes of Health (NIH) estimate, 90% of cells in the human body are bacterial, fungal, or otherwise non-human.(({{pubmed>long:17943116}})) Although many have concluded that bacteria surely enjoy a commensal relationship with their human hosts, only a fraction of the human microbiota has been characterized, much less identified. The sheer number of non-human genes represented by the human microbiota – there are millions in our "extended genome"(({{pubmed>long:20388071}})) compared to the nearly 23,000 in the human genome – implies we have just begun to fathom the full extent to which bacteria work to facilitate their own survival. (({{pubmed>long:28245427}}))	+	According to a recent National Institutes of Health (NIH) estimate, 90% of cells in the human body are bacterial, fungal, or otherwise non-human.(({{pmid>long:17943116}})) Although many have concluded that bacteria surely enjoy a commensal relationship with their human hosts, only a fraction of the human microbiota has been characterized, much less identified. The sheer number of non-human genes represented by the human microbiota – there are millions in our "extended genome"(({{pmid>long:20388071}})) compared to the nearly 23,000 in the human genome – implies we have just begun to fathom the full extent to which bacteria work to facilitate their own survival. (({{pmid>long:28245427}}))

	The NIH's ongoing initiative, the Human Microbiome Project, aspires to catalog the human microbiome, also referred to as the human metagenome. Emerging insights from environmental sampling studies have shown, for example, that //in vitro// based methods for culturing bacteria have drastically underrepresented the size and diversity of bacterial populations. One environmental sample of human hands found 100 times more species than had previously been detected using purely culture-based methods. Another study which also employed high throughput genomic sequencing discovered high numbers of hydrothermal vent eubacteria on prosthetic hip joints, a species once thought only to persist in the depths of the ocean.		The NIH's ongoing initiative, the Human Microbiome Project, aspires to catalog the human microbiome, also referred to as the human metagenome. Emerging insights from environmental sampling studies have shown, for example, that //in vitro// based methods for culturing bacteria have drastically underrepresented the size and diversity of bacterial populations. One environmental sample of human hands found 100 times more species than had previously been detected using purely culture-based methods. Another study which also employed high throughput genomic sequencing discovered high numbers of hydrothermal vent eubacteria on prosthetic hip joints, a species once thought only to persist in the depths of the ocean.
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-	Recent research has demonstrated that the diversity, prevalence and persistence of bacteria has been consistently underestimated. Microbes form most of the world's biomass: there are typically 40 million bacterial cells in a gram of soil and a million bacterial cells in a milliliter (gram) of fresh water.(({{pubmed>long:9618454}})) Studies have found bacteria in areas previously thought to be completely sterile. A broad diversity of bacteria were found at all of the "clean rooms" where NASA spacecraft are assembled and in spite of the highly desiccated, nutrient-bare conditions within.(({{pubmed>long:17655710}}))	+	Recent research has demonstrated that the diversity, prevalence and persistence of bacteria has been consistently underestimated. Microbes form most of the world's biomass: there are typically 40 million bacterial cells in a gram of soil and a million bacterial cells in a milliliter (gram) of fresh water.(({{pmid>long:9618454}})) Studies have found bacteria in areas previously thought to be completely sterile. A broad diversity of bacteria were found at all of the "clean rooms" where NASA spacecraft are assembled and in spite of the highly desiccated, nutrient-bare conditions within.(({{pmid>long:17655710}}))

	Bacteria are no less persistent or proliferative inside the human body.		Bacteria are no less persistent or proliferative inside the human body.

-	One prominent researcher [[http://news.bbc.co.uk/1/hi/health/6333137.stm\|called]] human skin a "virtual zoo of bacteria."(({{pubmed>long:17293459}})) Another compared the diversity in the human gut to a rain forest.(({{pubmed>long:17014427}})) The human gut alone contains on average: 40,000 bacterial species,(({{pubmed>long:18043225}})) 9 million unique bacterial genes and 100 trillion microbial cells.(({{pubmed>long:19562079}})) According to Asher Mullard, “Between them [the bacteria in our bodies], they harbor millions of genes, compared with the paltry 20,000 estimated in the human genome. To say that you are outnumbered is a massive understatement.”(({{pubmed>long:18509412}}))	+	One prominent researcher [[https://news.bbc.co.uk/1/hi/health/6333137.stm\|called]] human skin a "virtual zoo of bacteria."(({{pmid>long:17293459}})) Another compared the diversity in the human gut to a rain forest.(({{pmid>long:17014427}})) The human gut alone contains on average: 40,000 bacterial species,(({{pmid>long:18043225}})) 9 million unique bacterial genes and 100 trillion microbial cells.(({{pmid>long:19562079}})) According to Asher Mullard, “Between them [the bacteria in our bodies], they harbor millions of genes, compared with the paltry 20,000 estimated in the human genome. To say that you are outnumbered is a massive understatement.”(({{pmid>long:18509412}}))

-	The global initiative known as the Human Microbiome Project currently estimates that the microorganisms that live inside or on //Homo sapiens// outnumber somatic (body) and germ cells [germ cells as in gametes, not bacteria] by a factor of ten.(({{pubmed>long:17943116}})) To this point, only approximately 1% of this microbiota has been characterized and identified.(({{pubmed>long:17620602}})) The Human Microbiome Project aims to catalog the balance using an array of molecular sequencing techniques over the coming years.(({{pubmed>long:12037568}})) The combined genetic contributions of these microbes — in excess of 1,000,000 protein-coding genes — provide traits not encoded in our own genomes.(({{pubmed>long:12037568}}))	+	The global initiative known as the Human Microbiome Project currently estimates that the microorganisms that live inside or on //Homo sapiens// outnumber somatic (body) and germ cells [germ cells as in gametes, not bacteria] by a factor of ten.(({{pmid>long:17943116}})) To this point, only approximately 1% of this microbiota has been characterized and identified.(({{pmid>long:17620602}})) The Human Microbiome Project aims to catalog the balance using an array of molecular sequencing techniques over the coming years.(({{pmid>long:12037568}})) The combined genetic contributions of these microbes — in excess of 1,000,000 protein-coding genes — provide traits not encoded in our own genomes.(({{pmid>long:12037568}}))

-	Since the inception of the Human Microbiome Project in 2007, dozens of research teams have gathered data which redefine what it means to be human. Some commentators have gone so far as to refer to the human body as a superorganism whose "whose metabolism represents an amalgamation of microbial and human attributes."(({{pubmed>long:16741115}}))	+	Since the inception of the Human Microbiome Project in 2007, dozens of research teams have gathered data which redefine what it means to be human. Some commentators have gone so far as to refer to the human body as a superorganism whose "whose metabolism represents an amalgamation of microbial and human attributes."(({{pmid>long:16741115}}))


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	Researchers have long known that traditional methods for identifying bacteria are effective at identifying only a fraction of the bacteria in a given sample. New genomic based methods such as polymerase chain reaction (PCR) detect bacterial forms based on the presence of bacterial DNA or RNA. These new techniques are leading to some unexpected insights about bacteria.		Researchers have long known that traditional methods for identifying bacteria are effective at identifying only a fraction of the bacteria in a given sample. New genomic based methods such as polymerase chain reaction (PCR) detect bacterial forms based on the presence of bacterial DNA or RNA. These new techniques are leading to some unexpected insights about bacteria.

-	* Bacteria are everywhere including the world's most hostile environments – According to [[http://www.physorg.com/news131712233.html\|Penn State researcher Jennifer Loveland-Curtze]], “Microbes comprise up to one-third or more of the Earth’s biomass, yet fewer than 8,000 microbes have been described out of the approximately 3,000,000 that are presumed to exist,”	+	* Bacteria are everywhere including the world's most hostile environments – According to [[https://www.physorg.com/news131712233.html\|Penn State researcher Jennifer Loveland-Curtze]], “Microbes comprise up to one-third or more of the Earth’s biomass, yet fewer than 8,000 microbes have been described out of the approximately 3,000,000 that are presumed to exist,”
-	* NASA "clean rooms" – One would think that the the one place on Earth where bacteria do not exist is in the NASA "clean rooms" – the supposedly sterile places used to assemble aircraft. A 2007 research team compared the prevalence of bacteria found using traditional culture-based methods and ribosomal RNA gene sequence analysis. The four geographically diverse samples taken show a broad diversity in the types of bacteria able to grow in the most hostile environments including almost 100 types of bacteria, about 45 percent of which were previously unknown to science.(({{pubmed>long:17308177}})) The findings were something of a shock for NASA, an agency now forced to wonder exactly how many unknown pathogens have been taken to the moon and Mars.	+	* NASA "clean rooms" – One would think that the the one place on Earth where bacteria do not exist is in the NASA "clean rooms" – the supposedly sterile places used to assemble aircraft. A 2007 research team compared the prevalence of bacteria found using traditional culture-based methods and ribosomal RNA gene sequence analysis. The four geographically diverse samples taken show a broad diversity in the types of bacteria able to grow in the most hostile environments including almost 100 types of bacteria, about 45 percent of which were previously unknown to science.(({{pmid>long:17308177}})) The findings were something of a shock for NASA, an agency now forced to wonder exactly how many unknown pathogens have been taken to the moon and Mars.
-	* Two miles below the surface of a Greenland glacier – A Penn State team found viable "ultrasmall bacteria" in a glacial core(({{pubmed>long:16332755}})) – a habitat which is low-temperature, high-pressure, reduced-oxygen, and nutrient-poor. The core was estimated to be 120,000 years old.	+	* Two miles below the surface of a Greenland glacier – A Penn State team found viable "ultrasmall bacteria" in a glacial core(({{pmid>long:16332755}})) – a habitat which is low-temperature, high-pressure, reduced-oxygen, and nutrient-poor. The core was estimated to be 120,000 years old.
-	* Deepest layer of the earth's crust – A [[http://www.newscientist.com/article/mg20827874.800-life-is-found-in-deepest-layer-of-earths-crust.html\|2010 analysis]] of the deepest layer of the Earth's oceanic crust has revealed a new ecosystem living over a kilometer beneath our feet. It is the first time that life has been found in the crust's deepest layer.(({{pubmed>long:21079766}}))	+	* Deepest layer of the earth's crust – A [[https://www.newscientist.com/article/mg20827874.800-life-is-found-in-deepest-layer-of-earths-crust.html\|2010 analysis]] of the deepest layer of the Earth's oceanic crust has revealed a new ecosystem living over a kilometer beneath our feet. It is the first time that life has been found in the crust's deepest layer.(({{pmid>long:21079766}}))
-	[{{ :home:pathogenesis:types.jpeg?\|Intrapersonal and interpersonal variability of the human microbiome is profound. A [[http://www.ncbi.nlm.nih.gov/pubmed/20534435\|2012 study]] of the human vaginal microbiome found profound shifts over time and between subjects. Red bars indicate menses.}}]	+	[{{ :home:pathogenesis:types.jpeg?\|Intrapersonal and interpersonal variability of the human microbiome is profound. A [[https://www.ncbi.nlm.nih.gov/pubmed/20534435\|2012 study]] of the human vaginal microbiome found profound shifts over time and between subjects. Red bars indicate menses.}}]
-	* [[home:pathogenesis:microbiota:detecting#existence_of_microbes_in_healthy_tissue_supposed_to_be_sterile\|In tissue sites once deemed sterile]] – The Relman Lab at Stanford used real time PCR to target conserved regions of the bacterial 16S ribosomal DNA (rDNA). They concluded that there is a substantial and "normal" population of bacterial DNA sequences in the blood of even healthy individuals.(({{pubmed>long:11326021}}))	+	* [[home:pathogenesis:microbiota:detecting#existence_of_microbes_in_healthy_tissue_supposed_to_be_sterile\|In tissue sites once deemed sterile]] – The Relman Lab at Stanford used real time PCR to target conserved regions of the bacterial 16S ribosomal DNA (rDNA). They concluded that there is a substantial and "normal" population of bacterial DNA sequences in the blood of even healthy individuals.(({{pmid>long:11326021}}))
-	* Antibiotic resistant strains predate human discovery of antibiotics – In a 2011 //Nature// study ([[http://www.eurekalert.org/pub_releases/2011-08/mu-rta082511.php\|press release]]), researchers carefully dug ancient 30,000 year old permafrost sediments out of the Canadian Northwest and sequenced the bacterial DNA found in it.(({{pubmed>long:21881561}})) The team concluded that antibiotic resistance genes predate our use of antibiotics and offers the first direct evidence that antibiotic resistance is an ancient, naturally occurring phenomenon widespread in the environment. This should not be surprising especially when one considers that penicillin came from a mold, tetracycline and demeclocycline from a strep mutant while Vancomycin came from //Amycolatopsis orientalis//.	+	* Antibiotic resistant strains predate human discovery of antibiotics – In a 2011 //Nature// study ([[https://www.eurekalert.org/pub_releases/2011-08/mu-rta082511.php\|press release]]), researchers carefully dug ancient 30,000 year old permafrost sediments out of the Canadian Northwest and sequenced the bacterial DNA found in it.(({{pmid>long:21881561}})) The team concluded that antibiotic resistance genes predate our use of antibiotics and offers the first direct evidence that antibiotic resistance is an ancient, naturally occurring phenomenon widespread in the environment. This should not be surprising especially when one considers that penicillin came from a mold, tetracycline and demeclocycline from a strep mutant while Vancomycin came from //Amycolatopsis orientalis//.
-	* Each person has a unique mix of pathogens – A study led by Dr. Noah Fierer used a high-throughput method for PCR testing to identify the number and species of bacteria present on the hands of 51 undergraduate students leaving an exam room. Each student whose bacterial "fingerprint" – that is, their unique combination of bacteria – was sequenced, carried on average 3,200 bacteria from 150 species on their hands. Only five species were found on all the students’ hands, while any two hands – even belonging to the same person – had only 13% of their bacterial species in common.(({{pubmed>long:19004758}}))	+	* Each person has a unique mix of pathogens – A study led by Dr. Noah Fierer used a high-throughput method for PCR testing to identify the number and species of bacteria present on the hands of 51 undergraduate students leaving an exam room. Each student whose bacterial "fingerprint" – that is, their unique combination of bacteria – was sequenced, carried on average 3,200 bacteria from 150 species on their hands. Only five species were found on all the students’ hands, while any two hands – even belonging to the same person – had only 13% of their bacterial species in common.(({{pmid>long:19004758}}))
-	* Communities of people have distinctive mixes of microbes – Two human ethnic groups based in India, which could not be distinguished on the basis of human DNA markers, could be distinguished based on their patterns of //H. pylori// variation.(({{pubmed>long:15051885}}))	+	* Communities of people have distinctive mixes of microbes – Two human ethnic groups based in India, which could not be distinguished on the basis of human DNA markers, could be distinguished based on their patterns of //H. pylori// variation.(({{pmid>long:15051885}}))
-	* Communities of microbes associated with a disease may be more diverse than controls – asthma,(({{pubmed>long:21194740}})) bacterial vaginosis(({{pubmed>long:18487399}}))	+	* Communities of microbes associated with a disease may be more diverse than controls – asthma,(({{pmid>long:21194740}})) bacterial vaginosis(({{pmid>long:18487399}}))
-	* Communities of microbes associated with a disease may be less diverse than controls – irritable bowel syndrome,(({{pubmed>long:19606407}})) Crohn's disease,(({{pubmed>long:16188921}})) type I diabetes,(({{pubmed>long:20613793}}))AIDS(({{pubmed>long:18691828}}))	+	* Communities of microbes associated with a disease may be less diverse than controls – irritable bowel syndrome,(({{pmid>long:19606407}})) Crohn's disease,(({{pmid>long:16188921}})) type I diabetes,(({{pmid>long:20613793}}))AIDS(({{pmid>long:18691828}}))
-	* Microbial variability may be relatively unrelated to food intake – While Dumas has shown that there are significant inter-regional differences in metabolites,(({{pubmed>long:16579598}})) work on the oral microbiome implies this may not be due to food consumption. In studying the oral microbiome, Nasidzie //et al.// took saliva samples from people in twelve diverse regions throughout the world including China, Germany, Poland, Congo, Philippines, and Louisiana.(({{pubmed>long:19251737}})) His team concluded that "while there is significantly more diversity in bacterial genera compared from different individuals than from the same individual, the diversity among individuals from the same location is nearly the same as the diversity among individuals from different locations." The relative absence of variability between people in different regions implies that those factors which are highly variable, including food intake, may play a smaller than expected role in determining what at least a person's oral microbiota is. The Human Microbiome Research consortium concluded in 2012 that much of the diversity in healthy subjects remains unexplained.(({{pubmed>long:22699609}}))	+	* Microbial variability may be relatively unrelated to food intake – While Dumas has shown that there are significant inter-regional differences in metabolites,(({{pmid>long:16579598}})) work on the oral microbiome implies this may not be due to food consumption. In studying the oral microbiome, Nasidzie //et al.// took saliva samples from people in twelve diverse regions throughout the world including China, Germany, Poland, Congo, Philippines, and Louisiana.(({{pmid>long:19251737}})) His team concluded that "while there is significantly more diversity in bacterial genera compared from different individuals than from the same individual, the diversity among individuals from the same location is nearly the same as the diversity among individuals from different locations." The relative absence of variability between people in different regions implies that those factors which are highly variable, including food intake, may play a smaller than expected role in determining what at least a person's oral microbiota is. The Human Microbiome Research consortium concluded in 2012 that much of the diversity in healthy subjects remains unexplained.(({{pmid>long:22699609}}))
-	* Many bacteria cannot be cultured using traditional cultivation techniques – Using PCR, Fierer's team found that the hands of student subjects contained 332,000 genetically distinct bacteria belonging to 4,742 different species. 45% of the species detected were considered rare. This marked a hundred-fold increase in the number of bacterial species detected in previous studies that had relied on purely culture-based methods (such as the Petri dish) to characterize the human hand microbiota.(({{pubmed>long:19004758}})) These conclusions are supported by the aformentioned study of NASA clean rooms, which found that only 0.1 to 55% of viable cells found via PCR were able to grow on defined culture medium.(({{pubmed>long:17308177}}))	+	* Many bacteria cannot be cultured using traditional cultivation techniques – Using PCR, Fierer's team found that the hands of student subjects contained 332,000 genetically distinct bacteria belonging to 4,742 different species. 45% of the species detected were considered rare. This marked a hundred-fold increase in the number of bacterial species detected in previous studies that had relied on purely culture-based methods (such as the Petri dish) to characterize the human hand microbiota.(({{pmid>long:19004758}})) These conclusions are supported by the aformentioned study of NASA clean rooms, which found that only 0.1 to 55% of viable cells found via PCR were able to grow on defined culture medium.(({{pmid>long:17308177}}))
-	* Some microbes need very few genes to persist – The genome of the microsporidia //Encephalitozoon cuniculi// (a pathogen which infects rabbits) is widely recognized as a model for extreme reduction and compaction. At only 2.9 Mbp, the genome encodes approximately 2,000 densely packed genes and little else. However, the nuclear genome of its sister, //Encephalitozoon intestinalis//, is even more reduced; at 2.3 Mbp, it represents a 20% reduction from an already severely compacted genome.(({{pubmed>long:20865802}}))	+	* Some microbes need very few genes to persist – The genome of the microsporidia //Encephalitozoon cuniculi// (a pathogen which infects rabbits) is widely recognized as a model for extreme reduction and compaction. At only 2.9 Mbp, the genome encodes approximately 2,000 densely packed genes and little else. However, the nuclear genome of its sister, //Encephalitozoon intestinalis//, is even more reduced; at 2.3 Mbp, it represents a 20% reduction from an already severely compacted genome.(({{pmid>long:20865802}}))
-	* A number of bacteria never thought to exist in man, do, and in large numbers. – A 2007 study, for example, found [[http://www.divediscover.whoi.edu/hottopics/bacteria.html\|hydrothermal vent eubacteria]] on a prosthetic hip joint, which represents fully 6% of the bacteria sequenced and analyzed.(({{pubmed>long:17501992}})) Hydrothermal vent eubacteria otherwise grow best above 176°F (80°C).	+	* A number of bacteria never thought to exist in man, do, and in large numbers. – A 2007 study, for example, found [[https://www.divediscover.whoi.edu/hottopics/bacteria.html\|hydrothermal vent eubacteria]] on a prosthetic hip joint, which represents fully 6% of the bacteria sequenced and analyzed.(({{pmid>long:17501992}})) Hydrothermal vent eubacteria otherwise grow best above 176°F (80°C).
-	* At least in fruit flies, gut microbes can alter mating preferences – In a [[http://blogs.discovermagazine.com/notrocketscience/2010/11/01/gut-bacteria-change-the-sexual-preferences-of-fruit-flies/\|2010 study]], mating preference was achieved by dividing a population of //Drosophila melanogaster// and rearing one part on a molasses medium and the other on a starch medium. When the isolated populations were mixed, "molasses flies" preferred to mate with other molasses flies and "starch flies" preferred to mate with other starch flies. The mating preference appeared after only one generation and was maintained for at least 37 generations. Antibiotic treatment abolished mating preference, suggesting that the fly microbiota was responsible for the phenomenon.(({{pubmed>long:21041648}}))	+	* At least in fruit flies, gut microbes can alter mating preferences – In a [[https://blogs.discovermagazine.com/notrocketscience/2010/11/01/gut-bacteria-change-the-sexual-preferences-of-fruit-flies/\|2010 study]], mating preference was achieved by dividing a population of //Drosophila melanogaster// and rearing one part on a molasses medium and the other on a starch medium. When the isolated populations were mixed, "molasses flies" preferred to mate with other molasses flies and "starch flies" preferred to mate with other starch flies. The mating preference appeared after only one generation and was maintained for at least 37 generations. Antibiotic treatment abolished mating preference, suggesting that the fly microbiota was responsible for the phenomenon.(({{pmid>long:21041648}}))
-	* Bacteria practice altruism – In a 2010 //Nature// paper, James J. Collins and his colleagues exposed one culture of //Escherichia coli//—some strains of which colonize the human and animal gut; others of which are notorious for causing disease outbreaks—to increasing amounts of an antibiotic over time. When they periodically analyzed the levels of drug resistance in the colony, they saw something unexpected: although the entire population was thriving in the presence of the drug, only a few individual bacteria were actually resistant. Further analysis revealed that the resistant mutants were secreting a molecule called indole that thwarts their own growth but helps the rest of the population survive by activating drug-export pumps on the bacterial cell membranes.(({{pubmed>long:20811456}}))	+	* Bacteria practice altruism – In a 2010 //Nature// paper, James J. Collins and his colleagues exposed one culture of //Escherichia coli//—some strains of which colonize the human and animal gut; others of which are notorious for causing disease outbreaks—to increasing amounts of an antibiotic over time. When they periodically analyzed the levels of drug resistance in the colony, they saw something unexpected: although the entire population was thriving in the presence of the drug, only a few individual bacteria were actually resistant. Further analysis revealed that the resistant mutants were secreting a molecule called indole that thwarts their own growth but helps the rest of the population survive by activating drug-export pumps on the bacterial cell membranes.(({{pmid>long:20811456}}))