Members of the human gut microbiota involved in recovery from Vibrio cholerae infection

Abstract

Given the global burden of diarrheal diseases1, it is important to understand how members of the gut microbiota affect the risk for, course of, and recovery from disease in children and adults. The acute, voluminous diarrhea caused by Vibrio cholerae represents a dramatic example of enteropathogen invasion and gut microbial community disruption. We have conducted a detailed time-series metagenomic study of fecal microbiota collected during the acute diarrheal and recovery phases of cholera in a cohort of Bangladeshi adults living in an area with a high burden of disease2. We find that recovery is characterized by a pattern of accumulation of bacterial taxa that shows similarities to the pattern of assembly/maturation of the gut microbiota in healthy Bangladeshi children3. To define underlying mechanisms, we introduced into gnotobiotic mice an artificial community that was composed of human gut bacterial species that directly correlate with recovery from cholera in adults and are indicative of normal microbiota maturation in healthy Bangladeshi children3. One of the species, Ruminococcus obeum, exhibited consistent increases in its relative abundance upon V. cholerae infection of the mice. Follow-up analyses, including mono- and co-colonization studies, established that R. obeum restricts V. cholerae colonization, that R. obeum luxS [autoinducer-2 (AI-2) synthase] expression and AI-2 production increase significantly with V. cholerae invasion, and that R. obeum AI-2 causes quorum-sensing mediated repression of several V. cholerae colonization factors. Co-colonization with V. cholerae mutants disclosed that R. obeum AI-2 reduces Vibrio colonization/pathogenicity through a novel pathway that does not depend on the V. cholerae AI-2 sensor, LuxP. The approach described can be used to mine the gut microbiota of Bangladeshi or other populations for members that use autoinducers and/or other mechanisms to limit colonization with V. cholerae, or conceivably other enteropathogens.

Surface-attached molecules control Staphylococcus aureus quorum sensing and biofilm development

“…There is also interest in enhancing quorum-sensing-controlled behaviors in beneficial bacteria. For example, bacterial biofilm formation is essential in wastewater treatment and food processing, and, in the context of the microbiome, commensal bacteria play roles in fending off invading pathogens, presumably by relying on quorum-sensing-controlled traits 12,13 . Indeed, anti- and pro-quorum-sensing compounds have been developed and show promise in relevant model systems 14–17 .…”

Microbiome engineering: Current applications and its future

“…Humans Administration of SCFAs, LED209, tempol, AI-2, CAI-1 [18,19,26,[49][50][51][52][53]61] Treat or prevent disorders and diseases e.g. metabolic syndrome, obesity and cholera…”

“…Humans Engineered microbes that overexpress quorum sensing molecules [49][50][51][52] Treat bacterial infection and dysbiosis…”

Malnutrition, gutted

“…In Malawi, Gordon has shown that children with a protein deficiency disorder, called kwashiorkor, have a different type of gut community than their unaffected twin siblings (1). In Bangladesh, Gordon has identified a set of bacterial species associated with both healthy growth in children (2) and recovery from cholera in adults (3). Gordon has other ongoing research projects in India, Peru, South Africa, and Brazil.…”

“…Much of Gordon's research also involves transplanting human microbes into germfree mice for further analysis. By transplanting a community indicative of a healthy gut in Bangladeshi children, the researchers revealed a bacterial pathway that helps the gut ward off infections (3).…”