Enteric pathogen exploitation of the microbiota-generated nutrient environment of the gut

Abstract

Residing within the intestine is a large community of commensal organisms collectively termed the microbiota. This community generates a complex nutrient environment by breaking down indigestible food products into metabolites that are used by both the host and the microbiota. Both the invading intestinal pathogen and the microbiota compete for these metabolites, which can shape both the composition of the flora, as well as susceptibility to infection. After infection is established, pathogen mediated inflammation alters the composition of the microbiota, which further shifts the makeup of metabolites in the gastrointestinal tract. A greater understanding of the interplay between the microbiota, the metabolites they generate, and susceptibility to enteric disease will enable the discovery of novel therapies against infectious disease.

Profound Alterations of Intestinal Microbiota following a Single Dose of Clindamycin Results in Sustained Susceptibility to Clostridium difficile-Induced Colitis

“…Although it is possible that C. difficile directly impairs expansion of other microbial groups by suppression or competition for ecological niches, it is also possible that C. difficile infection indirectly modulates intestinal microbiota composition by augmenting mucosal inflammation. Indeed, intestinal inflammation induced by enteric pathogens has been shown to affect colonic bacteria density (28), suppress populations of indigenous intestinal bacteria (20), and otherwise alter microbiota composition in ways that favor colonization and expansion of exogenous microbial populations (28), including pathogenic bacteria (35). Our results indicate C. difficile infection induces intestinal inflammation that persists for at least 30 days.…”

Control of Clostridium difficile Physiopathology in Response to Cysteine Availability

“…Thus, according to the metabolites present in the small intestine and in the colon, toxin genes might be differentially expressed in the gut. Accordingly, formate and acetate (directly obtained from pyruvate) predominate in the small intestine, while the levels of propionate and butyrate are higher in the colon (84). Such a control has been described in Salmonella enterica serovar Typhimurium: formate acts as a diffusible signal to induce the expression of invasion genes in the small intestine, the site that is preferentially colonized by this enteropathogen, while butyrate is present at higher concentrations in the colon and represses these genes (85,86).…”

Glucocorticoids and the Intestinal Environment

“…They produce substances including vitamins, volatile or short-chain fatty acids (SCFAs) and polyamines which are absorbed throughout the intestinal wall and used directly by intestinal epithelial cells or other cells of the body [170,171]. SCFA profoundly influence gut barrier functions, host immunity, epithelial proliferation and bacterial pathogenesis [172]. Zheng et al [171] showed extensive gut microbiota modulation of host systemic metabolism involving shortchain fatty acids, tryptophan and tyrosine metabolism, and possibly a compensatory mechanism of indole-melatonin production.…”

“…Beneficial and pathogen microorganism compete with each other for the attachment sites and for nutrients, so microbiota and their products can prevent pathogen colonization directly. On the other hand, microbiota acts on barrier functions also indirectly by stimulating mucosal immune system [172]. The abundant antigenic stimulus supplied by microbiota and their products are essential for the stimulation of immune system cells locally and systemically [173][174][175].…”

“…It is estimated that this microbial community has 70-140 times more total genes than the human host. These functional inter-relationships between host and microbiota or two different genomes determine the health or disease state of the metazoan hosts and the balance among different microorganism populations [113,172,179]. It is well accepted that the intestinal microbiota involves in metabolome of the host, thus promotes actively fat accumulation and weight gain and sustains indirectly a lowgrade systemic inflammation especially when imbalanced, and consequently, enhances the risk for complex, multifactorial diseases such as insulin resistance, diabetes, obesity and cardiovascular diseases.…”