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ARS Home » Midwest Area » Lexington, Kentucky » Forage-animal Production Research » Research » Publications at this Location » Publication #350734
Title: Microbiota fermentation-NLRP3 axis shapes the impact of dietary fibers on intestinal inflammation

Author
item SINGH, VISHAL - UNIVERSITY OF TOLEDO
item YEOH, BENG SAN - PENNSYLVANIA STATE UNIVERSITY
item WALKER, RACHEL - PENNSYLVANIA STATE UNIVERSITY
item CAI, JINGWEI - PENNSYLVANIA STATE UNIVERSITY
item XIA, XIA - PENNSYLVANIA STATE UNIVERSITY
item SAHA, PIU - PENNSYLVANIA STATE UNIVERSITY
item SHEARER, GREGORY - UNIVERSITY OF CALIFORNIA
item PATTERSON, ANDREW - PENNSYLVANIA STATE UNIVERSITY
item Flythe, Michael
item CHASSAING, BENOIT - GEORGIA STATE UNIVERSITY
item GEWIRTZ, ANDREW - GEORGIA STATE UNIVERSITY
item VIJAY-KIMAR, MATAM - PENNSYLVANIA STATE UNIVERSITY

Submitted to: Gut
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/19/2018
Publication Date: N/A
Citation: N/A

Interpretive Summary: Agricultural scientists have a strict definition of the term fiber, but in human nutrition “fiber” includes a variety of complex carbohydrates. “Soluble dietary fiber” is generally considered beneficial for humans and animals. However, this study has revealed a potential health risk associated with inulin, a carbohydrate that is considered a “soluble" or "fermentable dietary fiber”. Dietary fibers have many beneficial effects on health but yet, at least in some cases, seem to exacerbate intestinal inflammation. Hence, IBD (inflammitory bowel disease) patients often refrain from consumption of healthy foods rich in these fibers. Our results support the notion that fermentable fibers indeed promote gut health and can dampen inflammation, however, consumption of some fermentable fibers such as inulin results in increased total bacterial load specifically Proteobacteria, in the gut, and elevated levels of butyrate, an inflammasome modulator, which, collectively, results in exacerbation of immune-mediated colitis. These findings suggest a strategy to balance consumption of various fibers so as to avoid high levels of butyrate as a means to achieve health-promoting effects of nourishing gut bacteria without promoting inflammation.

Technical Abstract: Diets rich in fiber, especially fermentable fiber, provide an array of health benefits. However, many inflammatory bowel disease patients report poor tolerance to fiber-rich foods while the impact of fiber in murine colitis models, especially the DSS model, has yielded conflicting results whether fibers ameliorate or exacerbate disease. Here, we examined how replacing the insoluble fiber cellulose with fermentable fibers inulin or pectin impacted murine colitis models resulting from immune dysregulation (IL-10 neutralization) and/or innate immune deficiency (TLR5KO). We observed that inulin potentiated colitis severity while pectin ameliorated it. Such inulin-induced exacerbation of colitis correlated with inulin preferentially increasing butyrate-producing bacteria, including Proteobacteria species, and, concomitantly levels of cecal butyrate. Blockade of butyrate production by metronidazole or hops beta-acids ameliorated colitis severity. Increased butyrate correlated with increased IL-1 activity while inhibition of the Nlrp3 inflammasome by genetic, pharmacologic, or dietary means markedly reduced colitis. While these results support the notion that fermentable fibers have potential to ameliorate colitis, they caution that elevated butyrate consumption can result in detrimental activation of the Nlrp3 inflammasome activation.