The Versalovic laboratory seeks to understand the nature of the mammalian gut microbiome and how gut bacteria (and probiotics) impact mucosal immunity and intestinal inflammation. Primary clinical interests are inflammatory bowel disease and colorectal cancer. The body site of primary interest is the mammalian intestine (small and large) using mouse models, mouse and human cell lines, and human specimens. Our group links the study of bacterial genomes and metagenomes to the systems biology of the mammalian intestines.

We are actively exploring microbiome replacement and manipulation of the intestinal microbiome as models of fecal transplantation programs in humans. Our aim is to cure disease by fundamentally changing the function or composition of the intestinal microbiome to prevent or treat disease phenotypes such as IBD and cancer. We believe that this strategy represents the microbial cell and gene therapy of the future.

Gut Microbiome, Inflammation and Immunity

Many patients suffer from inflammatory bowel disease (IBD; intestinal inflammation) and cancer associated with inflammation. Our laboratory studies intestinal inflammation as an opportunity to gain deeper insights into how specific microbes and the microbiome affect intestinal immunity. With respect to inflammation, mouse colitis models and patients with IBD are studied in order to examine how gut bacteria (commensal microbes) affect patterns of mucosal immunity and immune signaling pathways. Commensal bacteria suppress TNF/cytokine signaling and MAP kinases in epithelial and myeloid cells. Genes and pathways in the microbiome (such as amino acid decarboxylation pathways) have been identified as candidate anti-inflammatory and immunoregulatory modules of the microbiome.

Identification of bacterial genes and soluble mediators from the gut microbiome may result in the isolation of novel new drug candidates such as anti-inflammatory compounds. Biogenic amines and novel genes have recently been identified, and these genes and compounds can suppress intestinal inflammation in mouse colitis models. New strategies to replace, modify or transplant microbiomes in mouse models and patients will provide opportunities to change medicine and treat patients with debilitating chronic intestinal diseases such as refractory IBD.

Gut Microbiome and Cancer

Patients with IBD or chronic intestinal inflammation are at increased risk for colorectal cancer, and our goal is to reduce cancer risk by altering the microbiome (its composition and function). New projects will explore mechanisms of immunoregulation, regulation of cell proliferation, and cancer prevention by the gut microbiome. Intestinal microbes convert amino acids into anti-inflammatory compounds that may suppress intestinal inflammation and cancer in the intestine (colorectal cancer).

Nutrient metabolism by the microbiome may offer clues regarding the connections between diet, the gut microbiome, inflammation and cancer. Microbial metabolites may modulate cell proliferation, apoptosis, and susceptibility to inflammation and cancer. Epithelial cell proliferation and differentiation appears to be regulated by factors derived from commensal bacteria. Relationships between nutrition, intestinal inflammation, cell proliferation, and neoplasia can be explored comprehensively in the context of the microbiome and probiotics research.