Letter | Published:

Dietary emulsifiers impact the mouse gut microbiota promoting colitis and metabolic syndrome

Nature volume 519, pages 9296 (05 March 2015) | Download Citation

  • A Corrigendum to this article was published on 04 May 2016

Abstract

The intestinal tract is inhabited by a large and diverse community of microbes collectively referred to as the gut microbiota. While the gut microbiota provides important benefits to its host, especially in metabolism and immune development, disturbance of the microbiota–host relationship is associated with numerous chronic inflammatory diseases, including inflammatory bowel disease and the group of obesity-associated diseases collectively referred to as metabolic syndrome. A primary means by which the intestine is protected from its microbiota is via multi-layered mucus structures that cover the intestinal surface, thereby allowing the vast majority of gut bacteria to be kept at a safe distance from epithelial cells that line the intestine1. Thus, agents that disrupt mucus–bacterial interactions might have the potential to promote diseases associated with gut inflammation. Consequently, it has been hypothesized that emulsifiers, detergent-like molecules that are a ubiquitous component of processed foods and that can increase bacterial translocation across epithelia in vitro2, might be promoting the increase in inflammatory bowel disease observed since the mid-twentieth century3. Here we report that, in mice, relatively low concentrations of two commonly used emulsifiers, namely carboxymethylcellulose and polysorbate-80, induced low-grade inflammation and obesity/metabolic syndrome in wild-type hosts and promoted robust colitis in mice predisposed to this disorder. Emulsifier-induced metabolic syndrome was associated with microbiota encroachment, altered species composition and increased pro-inflammatory potential. Use of germ-free mice and faecal transplants indicated that such changes in microbiota were necessary and sufficient for both low-grade inflammation and metabolic syndrome. These results support the emerging concept that perturbed host–microbiota interactions resulting in low-grade inflammation can promote adiposity and its associated metabolic effects. Moreover, they suggest that the broad use of emulsifying agents might be contributing to an increased societal incidence of obesity/metabolic syndrome and other chronic inflammatory diseases.

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Accessions

Primary accessions

European Nucleotide Archive

Data deposits

Sequencing data are deposited in the European Nucleotide Archive under accession number PRJEB8035.

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Acknowledgements

This work was supported by NIH grant DK099071 and DK083890. B.C. is a recipient of the Research Fellowship award from the Crohn’s and Colitis Foundation of America (CCFA). We thank B. Zhang, L. Etienne-Mesmin, H. Q. Tran and E. Viennois for technical assistance.

Author information

Affiliations

  1. Center for Inflammation, Immunity and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, Georgia 30303, USA

    • Benoit Chassaing
    •  & Andrew T. Gewirtz
  2. Faculty of Medicine, Bar Ilan University, Safed, 13115, Israel

    • Omry Koren
  3. Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York 14853, USA

    • Julia K. Goodrich
    • , Angela C. Poole
    •  & Ruth E. Ley
  4. Digestive Diseases Division, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia 30322, USA

    • Shanthi Srinivasan

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Contributions

B.C. and A.T.G. conceived the project, designed the experiments, interpreted the results, and wrote the manuscript. B.C. performed all experiments and analysis with advice and guidance from O.K., J.K.G., and A.C.P. S.S. and R.E.L. guided experimental design and data interpretation.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Andrew T. Gewirtz.

Extended data

Supplementary information

PDF files

  1. 1.

    Supplementary Table 1

    This table contains analysis of taxonomic abundances at the phyla, class, order and family level. WT, IL10-/- and TLR5-/- mice were exposed to drinking water containing CMC or P80 (1.0%) for 12 weeks. Microbiota composition was analyzed. Taxonomic abundances were analyzed at different levels (phyla, class, order and family). All the significantly altered groups upon emulsifier exposure are highlighted in bold. p-values were calculated using a 2-tailed t-test.

  2. 2.

    Supplementary Table 2

    This table shows OTUs statistically different between water-treated group and emulsifier-treated group. WT, IL10-/- and TLR5-/- mice were exposed to drinking water containing CMC or P80 (1.0%) for 12 weeks. Microbiota composition was analyzed. Table lists all OTUs found to be statistically different between water-treated group and emulsifier-treated groups. All OTUs that were previously described to have mucolytic properties are highlighted in purple. p-values were calculated using a 2-tailed t-test.

  3. 3.

    Supplementary Table 3

    This table contains prevalence analysis of the OTUs found to be related to Helicobacter genus. WT, IL10-/- and TLR5-/- mice were exposed to drinking water containing CMC or P80 (1.0%) for 12 weeks. Microbiota composition was analyzed. Prevalence of the OTUs 470487, 2729098, 102480 and 3319464 (Greengenes Prok_MSA IDs), assigned to belong to the Helicobacter genus, were analyzed. p-values were calculated using a 2-tailed t-test.

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https://doi.org/10.1038/nature14232

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