1. The gastrointestinal mucosa in health, CDI, and UC
The gastrointestinal mucosa in health, CDI, and UC. (A) The healthy mucosa is characterized by a diverse microbiota that confers colonization resistance and proper immunomodulation; few freely available nutrients; low levels of primary bile salts relative to secondary bile salts; secretory antibody capable of sequestering commensals, pathogens, and other antigens; an intact barrier with healthy epithelial cells and thick layers of mucus containing antimicrobial peptides; few immune cells; and a cytokine milieu dominated by anti-inflammatory cytokines such as IL-10 and TGF-β.
The gastrointestinal mucosa in health, CDI, and UC. (A) The healthy mucosa is characterized by a diverse microbiota that confers colonization resistance and proper immunomodulation; few freely available nutrients; low levels of primary bile salts relative to secondary bile salts; secretory antibody capable of sequestering commensals, pathogens, and other antigens; an intact barrier with healthy epithelial cells and thick layers of mucus containing antimicrobial peptides; few immune cells; and a cytokine milieu dominated by anti-inflammatory cytokines such as IL-10 and TGF-β. (B) Disruption of the microbiota results in increased nutrients permissive for C. difficile growth (1) and high concentrations of primary bile salts relative to secondary bile salts (2). These changes promote C. difficile spore germination and growth to high concentrations within the intestine. C. difficile toxins damage epithelial cytoskeletal components, leading to cell death and ulcerations (3). Probiotics may promote colonization resistance through multiple mechanisms, including competition for nutrients and the generation of secondary bile salts that prevent C. difficile germination. Probiotics may also directly inhibit the growth of C. difficile by producing bacteriocins or other inhibitory compounds. Some probiotics produce antitoxin proteases and may stimulate antibody production to sequester C. difficile and toxin. Reinforcing epithelial barriers and modulating inflammation may also promote healing and limit injurious host responses to infection. (C) Ulcerative colitis is characterized by an altered microbiota of decreased diversity (1), damage to the gastrointestinal epithelium (2), as well as aberrant, overly inflammatory host immune responses (3). By helping to maintain a normal microbiota and reinforce the barrier function of the epithelium, probiotics may limit exposure to inflammatory signals. Modulation of the mucosal immune system, including the cytokine milieu, neutrophil infiltration and function, and T cell differentiation, may also help redress aberrant responses to luminal antigens and prevent host-mediated damage to the mucosa. Abbreviations: IEC, intestinal epithelial cell; IFN, interferon; IL, interleukin; TcdA and TcdB, C. difficile toxins A and B, respectively; TGF, transforming growth factor; TNF, tumor necrosis factor.
Lauren E. Hudson et al. Clin. Microbiol. Rev. 2017; doi: /CMR