Microbiota fermentation-NLRP3 axis shapes the impact of dietary fibres on intestinal inflammation

Abstract

ObjectiveDiets rich in fermentable fibres provide an array of health benefits; however, many patients with IBD report poor tolerance to fermentable fibre-rich foods. Intervention studies with dietary fibres in murine models of colonic inflammation have yielded conflicting results on whether fibres ameliorate or exacerbate IBD. Herein, we examined how replacing the insoluble fibre, cellulose, with the fermentable fibres, inulin or pectin, impacted murine colitis resulting from immune dysregulation via inhibition of interleukin (IL)-10 signalling and/or innate immune deficiency (Tlr5KO).DesignMice were fed with diet containing either cellulose, inulin or pectin and subjected to weekly injections of an IL-10 receptor (αIL-10R) neutralising antibody. Colitis development was examined by serological, biochemical, histological and immunological parameters.ResultsInulin potentiated the severity of αIL10R-induced colitis, while pectin ameliorated the disease. Such exacerbation of colitis following inulin feeding was associated with enrichment of butyrate-producing bacteria and elevated levels of caecal butyrate. Blockade of butyrate production by either metronidazole or hops β-acids ameliorated colitis severity in inulin-fed mice, whereas augmenting caecal butyrate via tributyrin increased colitis severity in cellulose containing diet-fed mice. Elevated butyrate levels were associated with increased IL-1β activity, while inhibition of the NOD-like receptor protein 3 by genetic, pharmacologic or dietary means markedly reduced colitis.ConclusionThese results not only support the notion that fermentable fibres have the potential to ameliorate colitis but also caution that, in some contexts, prebiotic fibres can lead to gut dysbiosis and surfeit colonic butyrate that might exacerbate IBD.

Dairy Propionibacterium freudenreichii ameliorates acute colitis by stimulating MUC2 expression in intestinal goblet cell in a DSS-induced colitis rat model

“…Prebiotic fibres show many beneficial effects including amelioration of inflammation in the colon and SCFAs produced from the fibres by SCFA-producing gut microbiota contribute to the beneficial effects. Although SCFAs, especially butyrate, have been known the beneficial effect on colitis, a recent study showed that the negative effect of butyrate on colitis in animal study 40 . Fermentable fibres altered microbiota composition, which induced excess butyrate production resulted in exacerbation of IBD.…”

Amoxicillin‐induced gut dysbiosis influences estrous cycle in mice and cytokine expression in the ovary and the caecum

“…Our group showed that amoxicillin‐induced dysbiosis promoted an immune imbalance, with an increased pro‐inflammatory profile in the caecum and the ovary, with upregulated IL‐1β cytokine gene expression and a decrease in IL‐10 expression in both organs even in the absence of bacterial translocation for other organs (Figure ). We evaluate the expression of both genes in the organs since when they are differentially expressed they represent or an important acute pro‐inflammatory cytokine (IL‐1β), that is associated with a variety of inflammatory pattern when gut microbiota is altered, 21 or IL‐10 as a classic anti‐inflammatory cytokine which is also related to balance the gut of inflammatory status 22 . Meijer et al, 2010, discussed that the changes in the ration of Firmicutes to Bacteroidetes directly affect the gut inflammatory status 23 .…”

Nutrition and gut health: the impact of specific dietary components – it's not just five-a-day

“…Much higher concentrations are commonly present in the colonic lumen (about 20 mM) (36,37) but the epithelium in health is shielded by its continuous adherent mucus layer (38) , moreover butyrate metabolism by surface epithelial cells adds to protection of the more sensitive stem cells at the crypt base (39) . The intriguing studies by Singh et al showing the pro-inflammatory effects of inulin and their mediation via butyrate (31) should prompt us to look again at the possible role of butyrate in ulcerative colitis. Roediger and colleagues reported several decades ago that faecal butyrate concentrations were raised (to 35 mM) in active ulcerative colitis compared with an average 14 mM in controls (40) .…”