Changes in dominant groups of the gut microbiota do not explain cereal-fiber induced improvement of whole-body insulin sensitivity

Abstract

BackgroundDiets high in cereal-fiber (HCF) have been shown to improve whole-body insulin sensitivity. In search for potential mechanisms we hypothesized that a supplemented HCF-diet influences the composition of the human gut microbiota and/or biomarkers of colonic carbohydrate fermentation.MethodsWe performed a randomized controlled 18-week intervention in group-matched overweight participants. Fecal samples of 69 participants receiving isoenergetic HCF (cereal-fiber 43 g/day), or control (cereal-fiber 14 g/day), or high-protein (HP, 28% of energy-intake, cereal-fiber 14 g/day), or moderately high cereal fiber/protein diets (MIX; protein 23% of energy-intake, cereal-fiber 26 g/day) with comparable fat contents were investigated for diet-induced changes of dominant groups of the gut microbiota, and of fecal short-chain fatty-acids (SCFA) including several of their proposed targets, after 0, 6, and 18-weeks of dietary intervention. In vitro fermentation of the cereal fiber extracts as used in the HCF and MIX diets was analyzed using gas chromatography. Diet-induced effects on whole-body insulin-sensitivity were measured using euglycaemic-hyperinsulinemic clamps and re-calculated in the here investigated subset of n = 69 participants that provided sufficient fecal samples on all study days.ResultsGut microbiota groups and biomarkers of colonic fermentation were comparable between groups at baseline (week 0). No diet-induced differences were detected between groups during this isoenergetic intervention, neither in the full model nor in uncorrected subgroup-analyses. The cereal-fiber extract as used for preparation of the supplements in the HCF and MIX groups did not support in vitro fermentation. Fecal acetate, propionate, and butyrate concentrations remained unchanged, as well as potential targets of increased SCFA, whereas valerate increased after 6-weeks in the HP-group only (p = 0.037). Insulin-sensitivity significantly increased in the HCF-group from week-6 (baseline M-value 3.8 ± 0.4 vs 4.3 ± 0.4 mg·kg-1·min-1, p = 0.015; full model 0-18-weeks, treatment-x-time interaction, p = 0.046).ConclusionsChanges in the composition of the gut microbiota and/or markers of colonic carbohydrate fermentation did not contribute explaining the observed early onset and significant improvement of whole-body insulin sensitivity with the here investigated HCF-diet.Trial registrationThis trial was registered at http://www.clinicaltrials.gov as NCT00579657

Impact of Diet Composition on Blood Glucose Regulation

“…An 18-week randomized controlled intervention in healthy subjects having increased intake of insoluble cereal fiber, supplemented by cereal fiber extracts twice daily, significantly improved whole-body insulin sensitivity, as measured using euglycemic-hyperinsulinemic clamps (Weickert et al, 2011a(Weickert et al, , 2011b. A previous intervention by Pereira and colleagues showed comparable results when investigating the effects of whole grain diets on whole-body insulin sensitivity (Pereira et al, 2002).…”

“…This effect also contributes to improved glucose metabolism ). However, in the Profimet study whole-body insulin sensitivity (Weickert, 2012) was significantly improved independent of various markers of colonic fermentation, SCFA profiles in faecal samples, and dominant groups of the gut microbiota (Weickert et al, 2011a(Weickert et al, , 2011b, indicating that further factors were involved in conveying improved insulin sensitivity upon the consumption of insoluble cereal fiber.…”

“…Furthermore, protein induced deterioration of insulin sensitivity has been observed in humans under conditions of restricted fat intake (30% of energy intake), both on whole-body and liver level, as measured using euglycemic hyperinsulinemic clamps combined with stable isotope techniques (Weickert et al, 2011a(Weickert et al, , 2011b. Interestingly, the way of protein administration seems to be of importance, and supplementation of insulin resistant rats with leucine through gavage, that is intermittent feeding, significantly lowered fasting glycemia compared with continuous administration through the drinking water (Zanchi et al 2012).…”

“…Improved whole-body insulin sensitivity by insoluble cereal fiber was suggested to be related to interference with the digestion and/or absorption of dietary protein and consequently reduced amino acid induced activation of the mammalian target of rapamycin (mTOR) S6 kinase 1 (S6K1) signaling pathway (Weickert et al, , 2011a(Weickert et al, , 2011b) that directly results in insulin resistance both in animal models and human intervention studies (Krebs et al, 2002;Um et al, 2004;Tremblay et al, 2005). Further mechanisms that may be involved could be cereal-fiber induced binding of bile acids and fiber-induced effects on gut hormones and metabolite profiles but this will need to be investigated in future studies.…”

The Epidemiologic Evidence and Potential Biological Mechanisms for a Protective Effect of Dietary Fiber on the Risk of Colorectal Cancer

“…In general, after prebiotics, bifidobacteria and lactobacilli increase and clostridia and coliforms decrease, but whether these bacteria are related to colorectal cancer is not known [44]. Weickert and colleagues [45] contrasted 43 g of fiber with 14 g of fiber (mostly cellulose and hemicellulose, and thus poorly fermentable) over 18 weeks in 69 people and measured butyrate producing species: no changes in species were seen with fiber, suggesting that at least for nonfermentable fiber, its potential protection from colorectal cancer is not via species change.…”