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Published on: May 2, 2018
Perturbation of the gut microbiome by Prevotella spp. enhances host susceptibility to mucosal inflammation
Aida Iljazovic1, Urmi Roy1, Eric J C Gálvez1,2
1Department of Microbial Immune Regulation, Helmholtz Center for Infection Research, Braunschweig, Germany.
Abstract:
Diverse microbial signatures within the intestinal microbiota have been associated with intestinal and systemic inflammatory diseases, but whether these candidate microbes actively modulate host phenotypes or passively expand within the altered microbial ecosystem is frequently not known. Here we demonstrate that colonization of mice with a member of the genus Prevotella, which has been previously associated to colitis in mice, exacerbates intestinal inflammation. Our analysis revealed that Prevotella intestinalis alters composition and function of the ecosystem resulting in a reduction of short-chain fatty acids, specifically acetate, and consequently a decrease in intestinal IL-18 levels during steady state. Supplementation of IL-18 to Prevotella-colonized mice was sufficient to reduce intestinal inflammation. Hence, we conclude that intestinal Prevotella colonization results in metabolic changes in the microbiota, which reduce IL-18 production and consequently exacerbate intestinal inflammation, and potential systemic autoimmunity.
Insights
Prevotella intestinalis exacerbates gut inflammation by altering microbial metabolism, reducing beneficial short-chain fatty acids and IL-18 levels. Restoring IL-18 levels can mitigate this inflammation.
Area of Science:
- Microbiology
- Immunology
- Gastroenterology
Background:
- Intestinal microbiota dysbiosis is linked to inflammatory diseases.
- The role of specific microbes like Prevotella in disease pathogenesis remains unclear.
Purpose of the Study:
- To investigate the causal role of Prevotella intestinalis in exacerbating intestinal inflammation.
- To elucidate the mechanisms by which Prevotella intestinalis impacts the gut ecosystem and host immunity.
Main Methods:
- Colonization of mice with Prevotella intestinalis.
- Analysis of gut microbiota composition and function.
- Measurement of short-chain fatty acids and IL-18 levels.
- Intervention with IL-18 supplementation.
Main Results:
- Prevotella intestinalis colonization exacerbated intestinal inflammation in mice.
- Prevotella intestinalis altered gut microbiota, reducing acetate production.
- A decrease in intestinal IL-18 levels was observed in colonized mice.
- IL-18 supplementation ameliorated inflammation in Prevotella-colonized mice.
Conclusions:
- Intestinal Prevotella colonization drives inflammation through metabolic alterations in the microbiota.
- Reduced IL-18 production is a key mechanism linking Prevotella to exacerbated inflammation.
- Prevotella may contribute to systemic autoimmunity via its impact on intestinal immunity.
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