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Our research group studies probiotics, intestinal microbial ecology, and the interactions of intestinal bacteria with the mammalian innate immune system. How pathogenic and commensal bacteria exchange information and communicate with the mucosal innate immune system (including the epithelium) is of fundamental importance in microbiology, immunology, cell biology, and the sciences of infection and inflammation. The medical importance stems from a keener understanding of the intestinal microbiota and its role in chronic inflammation.

Probiotic : Microbe Interactions

Approximately 500 different bacterial species inhabit the human intestine. Microbiomes of such astounding complexity include many examples of cell:cell (bacterial:bacterial and bacterial:host) communication and cell signaling. Bacterial:bacterial interactions of commensal Lactobacillus and pathogenic Clostridium or Helicobacter are being studied in order to understand quorum sensing and microbial signaling within complex populations. These studies are being performed using in vitro cell culture model systems and mouse models. Lactobacillus genomic microarrays and microbial proteomics are being used to studying molecular mechanisms of cell:cell interactions.

We are investigating factors produced by the intestinal microbiota, specifically Lactobacillus. Immunomodulins (soluble peptides or proteins) produced by bacteria may affect expression of chemokines or cytokines important for immunoregulation by epithelial cells and macrophages. Multiple Lactobacillus clones produce soluble peptides or proteins that downregulate expression of pro-inflammatory cytokines such as TNF-a in macrophages. We are also exploring the interactions of intestinal commensal Lactobacillus with intestinal epithelial cells. We expect to identific probiotic genes important for immunoregulation by bacteria and the corresponding probiotic factors. Host response gene and cell signaling pathways are being studied with high density microarrays and proteomics approaches.

 

Recent Publications (PubMed)

Versalovic J, Relman D. How bacterial communities expand functional repertoires. PLOS Biology. 2006;4:2193-2195.

Alyamani EJ, Brandt P, Peña JA, Major AM, Fox JG, Suerbaum S, Versalovic J. Helicobacter hepaticus catalase shares surface-predicted epitopes with mammalian catalases. Microbiology. 2007; 153: 1006-1016.

Peña JA, McNeil K, Fox JG, Versalovic J. (2002) Molecular evidence of Helicobacter cinaedi organisms in human gastric biopsies. J Clin Microbiol 40:1511-1513.

Pena JA and Versalovic J. (2003) Lactobacillus rhamnosus GG decreases TNF-a production in lipopolysaccharide-activated murine macrophages by a contact-independent mechanism. Cellular Microbiology 5:277-285.

Peña JA, Li SY, Wilson PH, Thibodeau S, Szary AJ, and Versalovic J. (2004) Genotypic and phenotypic studies of murine intestinal lactobacilli: species differences in mice with and without colitis. Appl and Environ Microb. 70:558-568.