Human Gut Symbiont Roseburia hominis Promotes and Regulates Innate Immunity

Abstract

ObjectiveRoseburia hominis is a flagellated gut anaerobic bacterium belonging to the Lachnospiraceae family within the Firmicutes phylum. A significant decrease of R. hominis colonization in the gut of ulcerative colitis patients has recently been demonstrated. In this work, we have investigated the mechanisms of R. hominis–host cross talk using both murine and in vitro models.DesignThe complete genome sequence of R. hominis A2-183 was determined. C3H/HeN germ-free mice were mono-colonized with R. hominis, and the host–microbe interaction was studied using histology, transcriptome analyses and FACS. Further investigations were performed in vitro and using the TLR5KO and DSS-colitis murine models.ResultsIn the bacterium, R. hominis, host gut colonization upregulated genes involved in conjugation/mobilization, metabolism, motility, and chemotaxis. In the host cells, bacterial colonization upregulated genes related to antimicrobial peptides, gut barrier function, toll-like receptors (TLR) signaling, and T cell biology. CD4+CD25+FoxP3+ T cell numbers increased in the lamina propria of both mono-associated and conventional mice treated with R. hominis. Treatment with the R. hominis bacterium provided protection against DSS-induced colitis. The role of flagellin in host–bacterium interaction was also investigated.ConclusionMono-association of mice with R. hominis bacteria results in specific bidirectional gene expression patterns. A set of genes thought to be important for host colonization are induced in R. hominis, while the host cells respond by strengthening gut barrier function and enhancing Treg population expansion, possibly via TLR5-flagellin signaling. Our data reveal the immunomodulatory properties of R. hominis that could be useful for the control and treatment of gut inflammation.

Beneficial effect of butyrate‐producing Lachnospiraceae on stress‐induced visceral hypersensitivity in rats

“…Our data revealed a positive correlation between four Lachnospiraceae‐related OTUs and occludin expression, and supplementation with R. hominis prevented the decreases in occludin mRNA and protein expression, accompanied by an increase in butyrate production in the intestinal contents. This is consistent with the finding that R. hominis colonization of germ‐free mice can affect intestinal barrier function genes . These results suggest the potential role of specific butyrate‐producing bacteria in preventing gut leakage through their metabolites.…”

“…This is consistent with the finding that R. hominis colonization of germ-free mice can affect intestinal barrier function genes. 39 These results suggest the potential role of specific butyrate-producing bacteria in preventing gut leakage through their metabolites. Moreover, it is reported that butyrate could induce MUC2 mRNA expression and MUC2 secretion in goblet-like cell, 40 as well as promote the assembly of occludin dependent on AMPK pathway.…”

The intestinal microbiota predisposes to traveller’s diarrhoea and to the carriage of multidrug-resistant Enterobacteriaceae after travelling to tropical regions

“…Consistently with our findings, these genera were depleted in 16S microbiota profiles of individuals suffering from post-transplantation [35] and nosocomial diarrhoea, including Clostridium difficile infection [36]. Moreover, Roseburia and Ruminococcus species have been shown to prevent gut inflammation by strengthening gut barrier function in mice [37] and by enhancing starch fermentation in humans [38], respectively. Subjects who did not experience diarrhoea during the travel had a richer and more diverse microbiota after travel than before.…”

Gut microbiota differences in elderly subjects between rural city Kyotango and urban city Kyoto: an age-gender-matched study

“…It has been reported that the abundance of Roseburia genus was less in several diseases (ulcerative colitis, type 2 diabetes, and neuronal diseases), and that this bacterium could serve as probiotics for restoration of beneficial flora. (22) Patterson et al (23) have demonstrated that mono-association of mice with Roseburia hominis bacteria results in specific bidirectional gene expression patterns. A set of genes thought to be important for host colonization are induced in Roseburia hominis, while the host cells respond by strengthening the gut barrier func-tion and enhancing regulatory T cell population expansion, possibly via TLR5-flagellin signaling.…”