The role of mucosal immunity and host genetics in defining intestinal commensal bacteria

Abstract

Purpose of review Dramatic advances in molecular characterization of the largely noncultivable enteric microbiota have facilitated better understanding of the composition of this complex ecosystem at broad phylogenetic levels. This review outlines current understanding of mechanisms by which commensal bacteria are controlled and shaped into functional communities by innate and adaptive immune responses, antimicrobial peptides produced by epithelial cells and host genetic factors. Recent findings Secretory IgA, which targets enteric bacteria, regulates the number, composition and function of luminal bacteria. Likewise, epithelial production of antimicrobial peptides help control enteric microbiota growth, translocation and perhaps composition. The developing role of innate signaling pathways, such as toll-like receptors and NOD2, is beginning to be studied, with dysbiosis following their genetic deletion. Inflammation and effector immune responses lead to decreased diversity and selective alterations of functionally active bacterial species such as Escherichia coli and Faecalibacterium prausnitzii that have proinflammatory and protective activities, respectively. Studies of humans, mice and comparative species indicate that both genetic and early environmental factors influence the development of a stable intestinal microbiota. Summary/implications Genetic and mucosal immunity strongly influence the composition and function of enteric commensal bacteria. This understanding should help develop strategies to correct dysfunctional altered microbiota in genetically susceptible individuals, better diagnose and correct potential dysbiosis in high risk individuals at a preclinical stage, and therapeutically target pathogenic bacterial species that help drive chronic inflammatory conditions.

Nod1 and Nod2 signaling does not alter the composition of intestinal bacterial communities at homeostasis

“…Instead, other components of the innate and adaptive immune system, acting separately or in synergy, may play a larger role in controlling the microbiota and maintaining a balanced environment. 32 For…”

Induction of Bacterial Antigen-Specific Colitis by a Simplified Human Microbiota Consortium in Gnotobiotic Interleukin-10 −/− Mice

“…Several human and murine studies have shown that host factors, including genetic polymorphisms, and environmental factors, such as maternal transmission, early life exposures, diet, infections, and antibiotics, strongly influence the composition of the intestinal microbiota (9,29). However, deep-sequencing studies of complex commensal microbiotas necessarily concentrate on family and genus community structure rather than individual species.…”

“…An altered intestinal microbial composition (dysbiosis) is associated with intestinal inflammation in human IBD and with cases of acute and chronic rodent experimental enterocolitis harboring complex enteric microbiotas, which are characterized by decreased bacterial diversity and an altered ratio of dominant bacterial species (9,10). In addition, rodent models monoassociated with bacteria relevant to the dysbiosis of IBD, such as certain Escherichia coli, Enterococcus faecalis, Bacteroides vulgatus, and Bacteroides thetaiotaomicron strains, demonstrated that single intestinal bacteria can selectively induce host inflammation and also provided insights into underlying disease mechanisms (6,(11)(12)(13).…”

Novel perspectives on therapeutic modulation of the gut microbiota

“…Prebiotics typically refer to selectively fermented nondigestible food ingredients or substances that specifically support the growth and activity of health-promoting bacteria that colonize the gastrointestinal tract . The general consensus is that low bacterial richness is associated with IBD and altered host metabolic markers such as increased body weight fat mass, insulin resistance and inflammation [Hansen et al 2010;Le Chatelier et al 2013]. Microbiota gene richness was predictive of a reduced response to low-caloric diet intervention in terms of weight loss and improvement of metabolism and inflammatory traits ].…”