Poster - Successive infection: a model for how metagenomic communities shift to become more pathogenic over time

Type: Poster presentation
Presented by: Amy Proal
Conference: Human Microbiome Research Conference
Location: Washington University, St. Louis, Missouri
Date: August 31 – September 1, 2010
Additional Content: PDF of poster


Recent studies have demonstrated that persistent microbial species such as Mtb, Borrelia, CMV, HIV, and EBV are able to suppress expression of TACO, TLR-2, and key endogenous antimicrobials such as cathelicidin and the beta-Defensins by dysregulating the VDR nuclear receptor. This marks such a logical survival mechanism that other less studied microbes have also likely evolved to slow VDR activity or the activity of other receptors involved in controlling the immune response. Each pathogen that decreases immune activity makes it easier for the host to pick up other pathogens, which themselves may further slow immune activity, creating a snowball effect. Thus, an inflammatory disease state may result from the combined pathogenicity of the sum of microbes, both bacterial and viral, that any one person accumulates over the course of a lifetime. As human genes are upregulated or downregulated by acquired components of the microbiota, the body shifts farther away from its natural state of homeostasis. Infected cells increasingly struggle to correctly produce human metabolites in the presence of numerous proteins and enzymes being created by pathogenic genomes. The process offers a framework for understanding how certain microbial populations may shift over time so that eventually people start to develop an inflammatory diagnosis, or gradually begin to present with symptoms of what is often deemed “normal” aging. We have developed a therapy for inflammatory disease that uses the VDR agonist Olmesartan to re-active the innate immune response. Many patients have reported significant improvement and/or objective markers indicating disease resolution, providing support for the above model.

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