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Published on: May 2, 2018
Mucus-penetrating microbiota drive chronic low-grade intestinal inflammation and metabolic dysregulation
Melissa C Kordahi1,2, Noëmie Daniel1,2, Andrew T Gewirtz3
1Microbiome-Host Interactions, Institut Pasteur, Université Paris Cité, INSERM U1306, CNRS UMR6047, Paris, France.
Abstract:
Metabolic syndrome is, in humans, associated with alterations in the composition and localization of the intestinal microbiota, including encroachment of bacteria within the colon's inner mucus layer. Possible promoters of these events include dietary emulsifiers, such as carboxymethylcellulose (CMC) and polysorbate-80 (P80), which, in mice, result in altered microbiota composition, encroachment, low-grade inflammation and metabolic syndrome. While assessments of gut microbiota composition have largely focused on fecal/luminal samples, we hypothesize an outsized role for changes in mucus microbiota in driving low-grade inflammation and its consequences. In support of this notion, we herein report that both CMC and P80 led to stark changes in the mucus microbiome, markedly distinct from those observed in feces. Moreover, transfer of mucus microbiota from CMC- and P80-fed mice to germfree mice resulted in microbiota encroachment, low-grade inflammation, and various features of metabolic syndrome. Thus, we conclude that mucus-associated bacteria are pivotal determinants of intestinal inflammatory tone and host metabolism.
Insights
Dietary emulsifiers like CMC and P80 alter gut mucus bacteria, leading to inflammation and metabolic syndrome. These mucus microbes, not fecal ones, drive these harmful health effects.
Area of Science:
- Microbiology
- Gastroenterology
- Metabolic Health
Background:
- Metabolic syndrome is linked to gut microbiota changes, including bacterial encroachment in the colon's mucus layer.
- Dietary emulsifiers, carboxymethylcellulose (CMC) and polysorbate-80 (P80), may promote these gut alterations and metabolic dysfunction.
Purpose of the Study:
- To investigate the role of mucus microbiota versus fecal microbiota in mediating the effects of CMC and P80.
- To determine if changes in the mucus microbiome drive low-grade inflammation and metabolic syndrome.
Main Methods:
- Mice were fed CMC or P80, and their fecal and mucus microbiomes were analyzed.
- Gut microbiota composition and bacterial encroachment were assessed.
- Germfree mice received fecal or mucus microbiota transplants from CMC/P80-fed mice.
Main Results:
- CMC and P80 significantly altered the mucus microbiome composition, distinct from fecal changes.
- Microbiota transfer from CMC/P80-fed mice induced bacterial encroachment, low-grade inflammation, and metabolic syndrome features in recipient mice.
- Mucus microbiota, not fecal microbiota, were responsible for transferring these detrimental effects.
Conclusions:
- The gut mucus microbiome plays a critical role in regulating intestinal inflammation.
- Alterations in mucus-associated bacteria are key drivers of metabolic syndrome.
- Dietary emulsifiers impact host metabolism through their effects on the mucus microbiome.
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