Effect of wheat bran derived prebiotic supplementation on gastrointestinal transit, gut microbiota, and metabolic health: a randomized controlled trial in healthy adults with a slow gut transit

Acute intake of the wheat bran extract Arabinoxylan-Oligosaccharide (AXOS) modulates the gut microbiota, improves stool characteristics and postprandial glycemia in healthy humans. Yet, little is known on how long-term AXOS intake influences gastrointestinal (GI) functioning, gut microbiota, and metabolic health. In this randomized, placebo-controlled, double-blind study, we evaluated the effects of AXOS intake on GI function and metabolic health in adults with slow GI transit without constipation. Forty-eight normoglycemic adults were included with whole-gut transit time (WGTT) of >35 h receiving either 15 g/day AXOS or placebo (maltodextrin) for 12-wks. The primary outcome was WGTT, and secondary outcomes included stool parameters, gut permeability, short-chain fatty acids (SCFA), microbiota composition, energy expenditure, substrate oxidation, glucose, insulin, lipids, gut hormones, and adipose tissue (AT) function. WGTT was unchanged, but stool consistency softened after AXOS. 12-wks of AXOS intake significantly changed the microbiota by increasing Bifidobacterium and decreasing microbial alpha-diversity. With a good classification accuracy, overall microbiota composition classified responders with decreased WGTT after AXOS. The incretin hormone Glucagon-like protein 1 was reduced after AXOS compared to placebo. Energy expenditure, plasma metabolites, AT parameters, SCFA, and gut permeability were unchanged. In conclusion, intake of wheat bran extract increases fecal Bifidobacterium and softens stool consistency without major effects on energy metabolism in healthy humans with a slow GI transit. We show that overall gut microbiota classified responders with decreased WGTT after AXOS highlighting that GI transit and change thereof were associated with gut microbiota independent of Bifidobacterium. NCT02491125.</p

Targeting Adipose Tissue Lipid Metabolism to Improve Glucose Metabolism in Cardiometabolic Disease

With Type 2 diabetes mellitus and cardiovascular disease prevalence on the rise, there is a growing need for improved strategies to prevent or treat obesity and insulin resistance, both of which are major risk factors for these chronic diseases. Impairments in adipose tissue lipid metabolism seem to play a critical role in these disorders. In the classical picture of intracellular lipid breakdown, cytosolic lipolysis was proposed as the sole mechanism for triacylglycerol hydrolysis in adipocytes. Recent evidence suggests involvement of several hormones, membrane receptors, and intracellular signalling cascades, which has added complexity to the regulation of cytosolic lipolysis. Interestingly, a specific form of autophagy, called lipophagy, has been implicated as alternative lipolytic pathway. Defective regulation of cytosolic lipolysis and lipophagy might have substantial effects on lipid metabolism, thereby contributing to adipose tissue dysfunction, insulin resistance, and related cardiometabolic (cMet) diseases. This review will discuss recent advances in our understanding of classical lipolysis and lipophagy in adipocyte lipid metabolism under normal and pathological conditions. Furthermore, the question of whether modulation of adipocyte lipolysis and lipophagy might be a potential therapeutic target to combat cMet disorders will be addressed

Effects of gut microbiota manipulation on ex vivo lipolysis in human abdominal subcutaneous adipocytes

The intestinal microbiota may contribute to the development of obesity by affecting host lipid metabolism and insulin sensitivity. To investigate the effects of microbiota manipulation on ex vivo basal and β-adrenergically-stimulated lipolysis in human adipocytes, 36 obese men were randomized to amoxicillin (broad-spectrum antibiotic), vancomycin (narrow-spectrum antibiotic) or placebo treatment (7 d, 1500 mg/d). Before and after treatment, ex vivo adipose tissue lipolysis was assessed under basal conditions and during stimulation with the non-selective β-agonist isoprenaline using freshly isolated mature adipocytes. Gene (targeted microarray) and protein expression were analyzed to investigate underlying pathways. Antibiotics treatment did not significantly affect basal and maximal isoprenaline-mediated glycerol release from adipocytes. Adipose tissue β-adrenoceptor expression or post-receptor signalling was also not different between groups. In conclusion, 7 d oral antibiotics treatment has no effect on ex vivo lipolysis in mature adipocytes derived from adipose tissue of obese insulin resistant men.</p

The effects of polyphenol supplementation on adipose tissue morphology and gene expression in overweight and obese humans

Dietary polyphenols have beneficial effects on adipose tissue mass and function in rodents, but human studies are scarce. In a randomized, placebo-controlled study, 25 (10 women) overweight and obese humans received a combination of the polyphenols epigallocatechin-gallate and resveratrol (282 mg/d, 80 mg/d, respectively, EGCG+RES, n = 11) or placebo (PLA, n = 14) supplementation for 12 weeks. Abdominal subcutaneous adipose tissue (SAT) biopsies were collected for assessment of adipocyte morphology and micro-array analysis. EGCG+RES had no effects on adipocyte size and distribution compared with PLA. However, we identified pathways contributing to adipogenesis, cell cycle and apoptosis were significantly downregulated by EGCG+RES versus PLA. Furthermore, EGCG+RES significantly decreased expression of pathways related to energy metabolism, oxidative stress, inflammation, and immune defense as compared with PLA. In conclusion, the SAT gene expression profile indicates a reduced cell turnover after 12-week EGCG+RES in overweight-obese subjects. It remains to be elucidated whether these alterations translate into long-term metabolic effects.</p

Arabinoxylan-Oligosaccharide Intake changes the microbiota and softens stool consistency without changes in gut transit and metabolic health in healthy adults

Prebiotic fibers may alter gastrointestinal (GI) transit time, microbiota composition and short chain fatty acid (SCFA) production, contributing to improved gut functionality and metabolic health. We investigated long-term effects of Arabinoxylan-Oligosaccharide (AXOS), a prebiotic dietary fiber on GI transit time, gut microbiota composition, and metabolic profile in adult participants.Methods: This randomized, placebo-controlled double-blind parallel study included 48 normoglycemic men and women (ages 20-55 y, body mass index (BMI) 19.8-30.5 kg/m2) with a slow whole-gut transit time (>35h) recruited during August 2015 to December 2016 in Maastricht, the Netherlands. Participants were randomly allocated to 12 weeks 15g/day AXOS or placebo (maltodextrin) intake. GI transit time, stool parameters, gut permeability, SCFA and microbiota composition were assessed before and after. Energy expenditure, substrate oxidation, glucose, insulin, lipids and incretin hormones were measured during a breakfast meal test before and after.Results: AXOS significantly changed the microbiota (p=0.05) mainly by increasing Bifidobacterium and decreased microbial alpha-diversity (P<.001) as compared to placebo. Whole-gut and upper intestinal transit were not affected, but stool consistency softened after AXOS (Bristol stool chart score 2.7 ± 0.19 to 3.3 ± 0.19, P<.01). Postprandial fat oxidation tended to increase (iAUC, P=.073) and early GLP-1 response (AUC0-90min, P=.005) was reduced after AXOS. Energy expenditure, plasma metabolites, SCFA concentrations and gut permeability were unchanged. Microbiota could classify responders in improved whole-gut transit after AXOS with an ([ROC] AUC 0.80%).Conclusion: AXOS intake, changed the microbiota, mainly increased fecal Bifidobacterium, tended to increase postprandial fat oxidation and decreased the early GLP-1 response. Whilst we did not observe changes in whole-gut transit time, overall microbiota could accurately classify responders with improved GI transit after AXOS intake

Supplementation of Diet With Galacto-oligosaccharides Increases Bifidobacteria, but Not Insulin Sensitivity, in Obese Prediabetic Individuals

Background & Aims: The gut microbiota affects host lipid and glucose metabolism, satiety, and chronic low-grade inflammation to contribute to obesity and type 2 diabetes. Fermentation end products, in particular the short-chain fatty acid (SCFA) acetate, are believed to be involved in these processes. We investigated the long-term effects of supplementation with galacto-oligosaccharides (GOS), an acetogenic fiber, on the composition of the human gut microbiota and human metabolism. Methods: We performed a double-blinded, placebo-controlled, parallel intervention study of 44 overweight or obese (body mass index, 28-40 kg/m2) prediabetic men and women (ages, 45-70 y) from October 2014 through October 2015 in Maastricht, The Netherlands. The participants were assigned randomly to groups who ingested 15 g GOS or isocaloric placebo (maltodextrin) daily with their regular meals for 12 weeks. Before and after this period, we collected data on peripheral and adipose tissue insulin sensitivity, fecal microbiota composition, plasma and fecal SCFA, energy expenditure and substrate oxidation, body composition, and hormonal and inflammatory responses. The primary outcome was the effect of GOS on peripheral insulin sensitivity, measured by the hyperinsulinemic-euglycemic clamp method. Results: Supplementation of diets with GOS, but not placebo, increased the abundance of Bifidobacterium species in feces by 5-fold (P = .009; q = 0.144). Microbial richness or diversity in fecal samples were not affected. We did not observe any differences in fecal or fasting plasma SCFA concentrations or in systemic concentrations of gut-derived hormones, incretins, lipopolysaccharide-binding protein, or other markers of inflammation. In addition, no significant alterations in peripheral and adipose tissue insulin sensitivity, body composition, and energy and substrate metabolism were found. Conclusions: Twelve-week supplementation of GOS selectively increased fecal Bifidobacterium species abundance, but this did not produce significant changes in insulin sensitivity or related substrate and energy metabolism in overweight or obese prediabetic men and women. ClincialTrials.gov number, NCT02271776.</p