| We co-exist with a very complex group of metabolically active resident bacteria, fungi and viruses that strongly influence our immune and mucosal barrier functions. In the normal state, a highly diverse microbiota educate mucosal and systemic immune responses, activating protective T cells, B cells and innate immune cells to secrete IL-10 and differentiate into Tregs and Tr1 regulatory T cells. A subset of resident bacteria, especially Clostridium subsets that secrete short-chain fatty acids such as butyrate and propionate and activate IL-10 production by regulatory T cells are protective in experimental colitis. Importantly, these Clostridium groups and other protective bacteria (Lachnospiraceae) are decreased during active IBD, in parallel with increased bacterial subsets such as E. coli, Klebsiella and Fusobacteria that can induce chronic experimental colitis in susceptible mice, including IL-10 deficient mice. Functionally aggressive invasive/adherent E. coli strains (AIEC), but not conventional E. coli strains, induce chronic, bacterial antigen-specific T cell-mediated colitis in selectively colonized gnotobiotic mice. AIEC are found in approximately 30% of patients with ileal Crohn’s disease. We present strong evidence that manipulating the dysbiotic microbiota of mice can both prevent and treat chronic T cell-mediated colitis, including “humanized” ex-germ-free mice colonized with human feces, laying the foundation for microbial-based therapies in human IBD. Data to date in IBD patients show variable results with fecal transplants and existing probiotics. We suggest that more targeted manipulations with known protective resident bacterial species, perhaps in conjunction with dietary therapies, may be more successful and provide a more physiologic and effective approach to treat and prevent recurrence of IBD compared with current immune-based treatments. |
