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Microbiota fermentation-NLRP3 axis shapes the impact of dietary fibres on intestinal inflammation
  1. Vishal Singh1,
  2. Beng San Yeoh2,
  3. Rachel E Walker3,
  4. Xia Xiao3,
  5. Piu Saha1,
  6. Rachel M Golonka1,
  7. Jingwei Cai4,
  8. Alexis Charles Andre Bretin5,
  9. Xi Cheng1,
  10. Qing Liu4,
  11. Michael D Flythe6,
  12. Benoit Chassaing5,7,
  13. Gregory C Shearer3,
  14. Andrew D Patterson4,
  15. Andrew T Gewirtz5,
  16. Matam Vijay-Kumar1,8
  1. 1Department of Physiology and Pharmacology, College of Medicine and Life Sciences, University of Toledo, Toledo, Ohio, USA
  2. 2Nutritional Sciences, Graduate Program in Immunology and Infectious Diseases, Pennsylvania State University, University Park, Pennsylvania, USA
  3. 3Department of Nutritional Sciences, Pennsylvania State University, University Park, Pennsylvania, USA
  4. 4Department of Veterinary and Biomedical Sciences, Pennsylvania State University, University Park, Pennsylvania, USA
  5. 5Center for Inflammation Immunity and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, Georgia, USA
  6. 6USDA-Agriculture Research Service, University of Kentucky Campus, Lexington, Kentucky, USA
  7. 7Neuroscience Institute, Institutefor Biomedical Sciences , Georgia State University, Atlanta, Georgia, USA
  8. 8Department of Medical Microbiology and Immunology, University of Toledo, Toledo, Ohio, USA
  1. Correspondence to Dr Matam Vijay-Kumar, Department of Physiology and Pharmacology, College of Medicine and Life Sciences, University of Toledo, Toledo, OH 43614, USA; MatamVijay.Kumar{at}


Objective Diets 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).

Design Mice 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.

Results Inulin 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.

Conclusion These 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.

  • inflammatory bowel disease
  • chronic ulcerative colitis
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  • Patient consent for publication Not required.

  • Contributors VS conceived the project, designed and performed the mouse experiments. Original observation was made by VS. BSY helped with histochemical staining and writing the manuscript. REW, GCS, JC, QL and ADP analysed SCFA in caecal contents and provided inputs for data interpretation. ACAB, XX, RMG and PS performed colonic gene expression and immune cell profiling. VS, BC and XC generated and analysed the microbiota data. MDF provided hops β-acid with intellectual inputs on bacterial fermentation. ATG assisted with data interpretation and study design. MV-K participated in the study design and directed the study. VS, ATG and MV-K wrote the manuscript.

  • Funding This work was supported by National Institutes of Health grants DK097865 (to MV-K), DK083890 (to ATG) and DK099071 (to ATG). VS is supported by research fellowship award (ID# 418507) and career development award (ID# 597229) from Crohn’s & Colitis Foundation (CCF). PS is supported by research fellowship award from CCF. BC is supported by a career development award fellowship from CCF and by an Innovator Award from the Kenneth Rainin Foundation.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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