A diet based on fiber-rich foods exerts benefits including not only improved gut health through conserving and restoring the human gut microbiome, but also potential beneficial effects on enteric infections, food allergies, metabolic disorders and even brain health. Besides this, dietary fiber has also been related to lower risk of all-cause mortality. However, the mechanisms underlying these effects have not yet been elucidated.
Two new mouse studies help us answer a critical nutrition-related question: Why is fiber good for us?
The first study, led by Prof. Andrew Gewirtz from the Centre for Inflammation, Immunity and Infection, Institute for Biomedical Sciences at Georgia State University (Atlanta, USA), has found that the fermentable fiber inulin prevents high-fat diet-induced metabolic syndrome in mice.
The researchers first put mice on a standard low-fiber, high-fat diet (HFD) -which is made from purified ingredients and consists of 35% fat by weight, 5% cellulose as a source of fiber, and no fermentable fiber. Mice fed this diet, as compared to normal chow -which is a low-fat assemblage of relatively unrefined plant and animal products containing 5% fat by weight and up to 25% fiber coming from different sources- develop increased adiposity as well as features of metabolic syndrome. In the mice on the HFD, a diet comprising 20% inulin reduced weight gain and both the adiposity -measured as the amount of epididymal, mesenteric, and subcutaneous fat- and adipocyte size. Supplementation of the HFD with inulin also lowered levels of cholesterol, prevented dysglycemia and reduced hepatosteatosis. However, enriching HFD with cellulose (non-fermentable fiber) led to modest reduced adiposity and dysglycemia. These results show that the fermentable fiber inulin was able to prevent metabolic syndrome induced by the HFD.
Regarding fiber’s direct impact on the gut ecosystem, inulin, but not cellulose, increased enterocyte proliferation and prevented gut atrophy. Inulin’s ability to promote enterocyte growth had an impact upon other cell types as it increased the levels of Paneth cells in the ileum, and it increased colon expression of tight junction proteins Occludin and Claudin-2. Enterocyte proliferation and colon mass have been previously correlated with protection against HFD-induced metabolic syndrome.
When it comes to assessing to what extent inulin’s protection against HFD-induced metabolic disease correlates with gut microbiota alterations, inulin but not cellulose fully restored the 10-fold reduction in total faecal bacterial loads promoted by the HFD. Specifically, inulin ameliorated HFD-induced increases of the relative abundance of Proteobacteria and increased Bifidobacteriaceae and Akkermansia, which is in agreement with a previous study in mice. However, inulin did not fully restore the gut microbiota composition of HFD-fed mice toward that of standard chow-fed mice. In contrast, enrichment of HFD with cellulose had a relatively mild impact on gut microbiota composition. Inulin also prevented HFD-induced gut microbiota infiltration into the mucus layer, an effect that was associated with restoration of the expression of antimicrobial peptide Reg3g in whole-colon tissue or in colon epithelial cells.
Antibiotic treatment reduced the ability of inulin to impact the colon, suppress adiposity, and improve glycemic control, which indicates gut microbiota was necessary for both inulin’s promotion of colon mass and beneficial effects on parameters of metabolic syndrome in mice.
The researchers also examined mechanisms by which the gut microbiota mediated inulin’s beneficial effects on the host. It was found that inulin’s promotion of colon mass and improvement of metabolic syndrome was driven by interleukin-22 (IL-22) -a cytokine induced by gut bacteria, which fortifies the intestine by promoting intestinal restitution following acute inflammation-. However, inulin’s effects did not rely on short-chain fatty acid production. Besides this, an inability to produce IL-22 in response to consumption of an inulin-enriched diet markedly impaired inulin’s ability to restore colon health and to suppress parameters of metabolic syndrome.
The second study, led by Prof. Fredrik Bäckhed from the Wallenberg Laboratory and Sahlgrenska Centre for Cardiovascular and Metabolic Research, Department of Molecular and Clinical Medicine, at the University of Gothenburg (Sweden), has found that the probiotic Bifidobacterium longum or the fermentable fiber inulin prevent the intestinal barrier defects of a Western style diet in mice.
When mice were put first on a low-fiber diet reproducing the Western style diet (WSD) for 8 weeks, they had an altered colonic microbiota composition that led to increased penetrability -which has been reported as a potential risk for inflammatory bowel disease in humans- and a reduced growth rate of the inner mucus layer after only 3 days. In genetically obese mice (Ob/Ob mice) that were fed a standard chow diet, two out of six mice displayed a highly penetrable inner mucus layer, therefore suggesting that the observed defective mucus layer may be a consequence of both diet and host metabolic factors. Besides this, although WSD feeding did not alter overall mucus protein composition, it resulted in increased mucus production by the host, which means that impairment of the mucus barrier may provoke a compensatory host response.
In a second experiment, the gut microbiota from chow-fed mice was transplanted to the mice fed a fiber-depleted diet and, as a result, recipient mice regained both barrier defects. Notably, the growth rate of the inner mucus layer positively correlated with relative abundance of Bifidobacterium, which was dramatically reduced between days 3 and 7 of WSD feeding (the period coinciding with the onset of the mucus defects). These data highlight that the gut microbiota is causal for the reduced mucus growth and increased penetrability.
Finally, the researchers tested whether the probiotic strain Bifidobacterium longum NCC 2705 (B. longum) or prebiotic oligofructose-enriched inulin could restore mucus properties. Administration of B. longum restored mucus growth, whereas administration of the fermentable fiber inulin prevented increased mucus penetrability in Western style diet-fed mice. These results show that the WSD-induced increase in mucus penetrability and decrease in mucus growth rate are separate events and both interventions may open up new possibilities in the management of diseases with colonic mucus deterioration.
On the whole, the study by Zou et al. shows that the fermentable fiber inulin’s benefits on metabolic syndrome are mediated via the gut microbiota to increase intestinal epithelial cell proliferation, prevent colonic atrophy, and reduce microbiota infiltration to the mucus layer. The second study by Schroeder et al. adds to the former one that WSD-mediated alterations of the gut microbiota composition cause defects of the inner mucus layer. Bifidobacterium longum or inulin supplements prevent mucus defects and could open new potential management strategies for diseases with an affected mucus layer, such as ulcerative colitis.
References:
Zou J, Chassaing B, Singh V, et al. Fiber-mediated nourishment of gut microbiota protects against diet-induced obesity by restoring IL-22-mediated colonic health. Cell Host Microbe. 2017; doi: 10.1016/j.chom.2017.11.003.
Schroeder BO, Birchenough GMH, Ståhlman M, et al. Bifidobacteria or fiber protects against diet-induced microbiota-mediated colonic mucus deterioration. Cell Host Microbe. 2017; doi: 10.1016/j.chom.2017.11.004.
