Am J Physiology, 2018., https://doi.org/10.1152/ajpendo.00391.2018

Microbial fermentation of flaxseed fibers modulates the transcriptome of GPR41-expressing enteroendocrine cells and protects mice against diet-induced obesity

Arora, T Rudenko, O Lihme Egerod, K Husted AS et al.

Abstract

Dietary fibers, an integral part of the human diet, require the enzymatic activity of the gut microbiota for complete metabolism into short chain fatty acids (SCFAs). SCFAs are important modulators of host metabolism and physiology and act in part as signaling molecules by activating G-protein coupled receptors (GPR) such as GPR41. Flaxseed fibers improve metabolism in rodents and mice, but their fermentation profiles, effects on enteroendocrine cells and associated metabolic benefits are unknown. We fed GPR41-RFP mice, an enteroendocrine reporter mouse strain, chow, high fat diet (HFD) or HFD supplemented either with 10% non-fermentable fiber cellulose or fermentable flaxseed fibers for 12 weeks to assess changes in cecal gut microbiota, enteroendocrine cell transcriptome in ileum and colon, and physiological parameters. We observed that flaxseed fibers restructured the gut microbiota and promoted proliferation of the genera Bifidobacterium and Akkermansiacompared with HFD. The shifts in cecal bacterial composition restored levels of the SCFAs butyrate similar to the chow diet, resulting in colonic, but not ileal, enteroendocrine cell transcriptional changes in genes related to cell cycle, mRNA and protein transport compared with HFD. Consistent with effects on enteroendocrine functions, flaxseed fibers also protected mice from diet-induced obesity, potentially by preventing reduction in energy expenditure induced by HFD. Our study shows that flaxseed fibers alter cecal microbial ecology, are fermented to SCFAs in cecum, and modulate enteroendocrine cell transcriptome in colon, which may contribute to their metabolically favorable phenotype.

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Key Points

Flaxseed fibers that ferment in the gut influence microbiota that can improve metabolic health, while protecting against diet-induced obesity.  Gut microbiota play a significant role in weight regulation and glucose tolerance, which is how the body processes sugar. Fiber is broken down in the gut via a process called fermentation. This process may positively affect the digestive system by increasing fatty acids, which in turn reduce the production of fat tissue in the body and improve immune function. In this study mice were assigned to four different diets: a standard diet that contained 4.6 percent soy-based fiber (“control”).; a high-fat diet that contained no fiber (“high-fat”); a high-fat diet that contained 10 percent indigestible cellulose fiber (“cellulose”); a high-fat diet that contained 10 percent flaxseed fiber (“flaxseed”). The high-fat group had fewer bacteria associated with improved metabolic health, lower levels of beneficial fatty acids and more of a bacterium linked to obesity when compared to the other groups.  Bacteria levels in both the cellulose and flaxseed groups returned to healthier levels when compared to the high-fat group. The flaxseed group was more physically active and had less weight gain than the other high-fat diet groups. Mice that received flaxseed supplements also had better glucose control and levels of beneficial fatty acids that were comparable to the healthy control group. When examining the cecal contents, the evidence was found that the bacteria present ferment fibers from the thick, glue-like layer of the flaxseed shell. The bacteria that perform fermentation then produce more beneficial fatty acids. The data suggest that flaxseed fiber supplementation affects the host metabolism by increasing energy expenditure and reducing obesity as well as improving glucose tolerance.