Dietary macronutrients and the gut microbiome: a precision nutrition approach to improve cardiometabolic health.

Accumulating evidence indicates that the gut microbiome is an important regulator of body weight, glucose and lipid metabolism, and inflammatory processes, and may thereby play a key role in the aetiology of obesity, insulin resistance and type 2 diabetes. Interindividual responsiveness to specific dietary interventions may be partially determined by differences in baseline gut microbiota composition and functionality between individuals with distinct metabolic phenotypes. However, the relationship between an individual's diet, gut microbiome and host metabolic phenotype is multidirectional and complex, yielding a challenge for practical implementation of targeted dietary guidelines. In this review, we discuss the latest research describing interactions between dietary composition, the gut microbiome and host metabolism. Furthermore, we describe how this knowledge can be integrated to develop precision-based nutritional strategies to improve bodyweight control and metabolic health in humans. Specifically, we will address that (1) insight in the role of the baseline gut microbial and metabolic phenotype in dietary intervention response may provide leads for precision-based nutritional strategies; that (2) the balance between carbohydrate and protein fermentation by the gut microbiota, as well as the site of fermentation in the colon, seems important determinants of host metabolism; and that (3) 'big data', including multiple omics and advanced modelling, are of undeniable importance in predicting (non-)response to dietary interventions. Clearly, detailed metabolic and microbial phenotyping in humans is necessary to better understand the link between diet, the gut microbiome and host metabolism, which is required to develop targeted dietary strategies and guidelines for different subgroups of the population.

Distal colonic transit is linked to gut microbiota diversity and microbial fermentation in humans with slow colonic transit.

Longer colonic transit time and hard stools are associated with increased gut microbiota diversity. Here, we investigate to what extent quantitative measures of (segmental) colonic transit time were related to gut microbiota composition, microbial metabolites, and gut-related parameters in a human cross-sectional study. Using radiopaque markers, (segmental) colonic transit time (CTT) was measured in 48 lean/overweight participants with long colonic transit but without constipation. Fecal microbiota composition was determined using 16S rRNA gene amplicon sequencing. Associations between gastrointestinal transit (segmental CTT and stool frequency and consistency), microbiota diversity and composition, microbial metabolites [short-chain fatty acids (SCFA), branched-chain fatty acids, and breath hydrogen], habitual diet, and gut-related host parameters [lipopolysaccharide-binding protein (LBP) and fecal calprotectin] were investigated using univariate and multivariate approaches. Long descending (i.e., distal) colonic transit was associated with increased microbial α-diversity but not with stool consistency. Using unweighted and weighted UniFrac distance, microbiota variation was not related to (segmental) CTT but to demographics, diet, plasma LBP, and fecal calprotectin. Bray-Curtis dissimilarity related only to stool consistency. Rectosigmoid and descending colonic transit were negatively associated with fecal SCFA and plasma acetate, respectively. This study suggests that the distal colon transit may affect not only microbiota diversity but also microbial metabolism.NEW & NOTEWORTHY We extend previous findings showing that long distal colonic transit time influences microbial diversification and fermentation, whereas stool consistency is related to microbiota composition in humans with a long colonic transit. This study puts the importance of the (distal) colonic site in microbiota ecology forward, which should be considered in future therapeutic studies targeting, for instance, short-chain fatty acid production to improve metabolic health.

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.

Acetate: a diet-derived key metabolite in energy metabolism: good or bad in context of obesity and glucose homeostasis?

PURPOSE OF REVIEW: To highlight recent research findings on effects of the short-chain fatty acid acetate in the control of body weight, insulin sensitivity, and glucose homeostasis. For this purpose, relevant animal and human in-vivo studies were reviewed and putative mechanisms and pathways were discussed. RECENT FINDINGS: Animal and human in-vivo studies provide strong indications for a beneficial role of orally ingested or colonically derived acetate, in the energy and substrate metabolism, thereby preventing or reversing the obese insulin-resistant phenotype. However, data from rodents are conflicting and indicate that an increased acetate turnover promotes body weight gain and insulin resistance. A reason for these controversies may be related to the mode and site of acetate administration, as well as to the species and the metabolic phenotype of animals used. SUMMARY: Overall, animal and human data suggest a direct regulatory role of acetate in several pathways involved in energy expenditure and fat utilization. In addition, acetate stimulates the release of gut-derived satiety-stimulating hormones and might regulate the inflammatory state. However, human intervention studies are required to evaluate the recent 'acetate discrepancies' and to confirm whether an increase in the acetate availability is a promising approach for the prevention and management of obesity and associated impairments in glucose and insulin metabolism.

Distal, not proximal, colonic acetate infusions promote fat oxidation and improve metabolic markers in overweight/obese men.

Gut microbial-derived short-chain fatty acids (SCFA) are believed to affect host metabolism and cardiometabolic risk factors. The present study aim was to investigate the effects of proximal and distal colonic infusions with the SCFA acetate on fat oxidation and other metabolic parameters in men. In this randomized, double-blind crossover trial, six overweight/obese men [body mass index (BMI) 25-35 kg/m2] underwent two experimental periods: one with distal and one with proximal colonic sodium acetate infusions. A feeding catheter was endoscopically positioned at the beginning of each period and remained in the colon for three consecutive test days, enabling colonic acetate (100 or 180 mmol/l) or placebo infusion during fasting conditions and after an oral glucose load (postprandial). Fat oxidation and energy expenditure were measured using an open-circuit ventilated hood system and blood samples were repeatedly collected for 2 h during fasting and postprandial conditions. Distal colonic 180 mmol/l acetate infusions increased fasting fat oxidation (1.78±0.28 compared with -0.78±0.89 g fat 2 h-1, P=0.015), fasting peptide YY (PYY, P=0.01) and postprandial glucose and insulin concentrations (P<0.05), and tended to increase fasting plasma acetate (P=0.069) compared with placebo. Distal 100 mmol/l acetate administration tended to decrease fasting tumour necrosis factor-α (TNF-α; P=0.067) compared with placebo. In contrast, proximal colonic acetate infusions showed no effects on substrate metabolism, circulating hormones or inflammatory markers. In conclusion distal colonic acetate infusions affected whole-body substrate metabolism, with a pronounced increase in fasting fat oxidation and plasma PYY. Modulating colonic acetate may be a nutritional target to treat or prevent metabolic disorders.

The role of polydextrose in body weight control and glucose regulation.

PURPOSE OF REVIEW: The purpose of this review was to highlight recent research developments on effects of the dietary fibre polydextrose (PDX) on appetite, satiety and energy intake and glucose metabolism. For this purpose, clinically relevant human studies were reviewed and putative mechanisms and pathways were discussed. RECENT FINDINGS: A number of acute human intervention studies provide strong indications for an energy and glucose metabolism-regulating role of PDX. These effects might be mediated via a reduced gastro-intestinal transit reducing glycaemia and insulinemia after PDX ingestion and the potential of PDX as soluble dietary fibre to alter the intestinal microbial composition, which might lead to changes in signalling in both peripheral and central pathways involved in energy metabolism and glucose homeostasis. SUMMARY: In acute studies, PDX seems to have an inhibiting effect on energy intake and satiety and to reduce glycaemic and insulinemic response through effect on gastro-intestinal transit time and macronutrient absorption as well as through effects of the microbial products such as short-chain fatty acids on energy and substrate metabolism. In particular, well controlled human intervention studies are required to confirm these effects in the long term. Overall, supplement PDX to the daily diet may be a promising approach for the management and treatment of obesity and associated metabolic disorders.

Intestinal gases as a non-invasive measurement of microbial fermentation and host health.

Microbial fermentation and associated products provide insights into the gut microbiota-host relationship. Here, we propose using improved technologies that allow non-invasive, real-time measurements of intestinal gases as a metric for microbial fermentation. This approach has the potential to provide a basis for personalized interventions that improve host metabolic health.

2'-fucosyllactose alone or combined with resistant starch increases circulating short-chain fatty acids in lean men and men with prediabetes and obesity.

Background: Infusion of short-chain fatty acids (SCFA) to the distal colon beneficially affects human substrate and energy metabolism. Here, we hypothesized that the combination of 2'-fucosyllactose (2'-FL) with resistant starch (RS) increases distal colonic SCFA production and improves metabolic parameters. Methods: In this randomized, crossover study, 10 lean (BMI 20-24.9 kg/m2) and nine men with prediabetes and overweight/obesity (BMI 25-35 kg/m2) were supplemented with either 2'-FL, 2'-FL+RS, or placebo one day before a clinical investigation day (CID). During the CID, blood samples were collected after a overnight fast and after intake of a liquid high-fat mixed meal to determine plasma SCFA (primary outcomes). Secondary outcomes were fasting and postprandial plasma insulin, glucose, free fatty acid (FFA), glucagon-like peptide-1, and peptide YY concentrations. In addition, fecal SCFA and microbiota composition, energy expenditure and substrate oxidation (indirect calorimetry), and breath hydrogen excretion were determined. Results: In lean men, supplementation with 2'-FL increased postprandial plasma acetate (P = 0.017) and fasting H2 excretion (P = 0.041) compared to placebo. Postprandial plasma butyrate concentration increased after 2'-FL and 2'-FL+RS as compared to placebo (P < 0.05) in lean men and men with prediabetes and overweight/obesity. Additionally, 2'-FL+RS decreased fasting and postprandial plasma FFA concentrations compared to placebo (P < 0.05) in lean men. Conclusion: Supplementation of 2'-FL with/without RS the day before investigation increased systemic butyrate concentrations in lean men as well as in men with prediabetes and obesity, while acetate only increased in lean men. The combination of 2'-FL with RS showed a putatively beneficial metabolic effect by lowering plasma FFA in lean men, indicating a phenotype-specific effect. Clinical trial registration: nr. NCT04795804.

Butyrate to combat obesity and obesity-associated metabolic disorders: Current status and future implications for therapeutic use.

Evidence is increasing that disturbances in the gut microbiome may play a significant role in the etiology of obesity and type 2 diabetes. The short chain fatty acid butyrate, a major end product of the bacterial fermentation of indigestible carbohydrates, is reputed to have anti-inflammatory properties and positive effects on body weight control and insulin sensitivity. However, whether butyrate has therapeutic potential for the treatment and prevention of obesity and obesity-related complications remains to be elucidated. Overall, animal studies strongly indicate that butyrate administered via various routes (e.g., orally) positively affects adipose tissue metabolism and functioning, energy and substrate metabolism, systemic and tissue-specific inflammation, and insulin sensitivity and body weight control. A limited number of human studies demonstrated interindividual differences in clinical effectiveness suggesting that outcomes may depend on the metabolic, microbial, and lifestyle-related characteristics of the target population. Hence, despite abundant evidence from animal data, support of human data is urgently required for the implementation of evidence-based oral and gut-derived butyrate interventions. To increase the efficacy of butyrate-focused interventions, future research should investigate which factors impact treatment outcomes including baseline gut microbial activity and functionality, thereby optimizing targeted-interventions and identifying individuals that merit most from such interventions.

Butyrate and hexanoate-enriched triglycerides increase postprandrial systemic butyrate and hexanoate in men with overweight/obesity: A double-blind placebo-controlled randomized crossover trial.

Background: Short chain fatty acids (SCFA) are increasingly recognized for their potential ability to alleviate obesity-associated chronic low-grade inflammation and disturbed energy homeostasis. Evidence suggests that an increase in circulating SCFA might be necessary to induce beneficial alterations in energy metabolism. Objective: To compare the bioaccessibility of two different SCFA-enriched triglycerides: Akovita SCT (butyrate and hexanoate esterified with long chain fatty acids) and tributyrin/caproin (solely butyrate and hexanoate) and investigate whether the SCFA from orally administrated Akovita SCT reach the circulation and affect postprandial metabolism in men with overweight/obesity. Methods: The site, speed, and amount of SCFA release from Akovita SCT and tributyrin/caproin were assessed in a validated In vitro Model of the stomach and small intestine (TIM-1). Subsequently, a double-blind placebo-controlled randomized crossover study was conducted at Maastricht University with fourteen men with overweight/obesity (BMI 25-35 kg/m2) of which twelve men finished all testdays and were included for analysis. The participants received a liquid high fat mixed meal test containing either a low (650 mg), medium (1,325 mg), or high dose (2,000 mg) of Akovita SCT or a placebo (sunflower oil) in randomized order. Blood was sampled at baseline and after ingestion for 6 h for the primary outcome plasma butyrate and hexanoate concentration. Secondary outcomes included hydrogen breath, appetite, gastrointestinal complaints, circulating glucagon-like peptide 1, free fatty acids, glucose, triglycerides, insulin, and cytokines concentrations. Results: In TIM-1, tributyrin/caproin was rapidly cleaved in the gastric compartment whereas the release of SCFA from Akovita SCT occurred predominantly in the small intestine. In vivo, all doses were well-tolerated. The medium dose increased (P < 0.05) and the high dose tended to increase (P < 0.10) postprandial circulating butyrate and both doses increased circulating hexanoate (P < 0.05) compared to placebo. Nevertheless, Akovita SCT supplementation did not affect any secondary outcomes compared to placebo. Conclusion: Esterifying SCFA-enriched triglycerides with long chain fatty acids delayed SCFA release from the glycerol backbone. Akovita SCT increased postprandial circulating butyrate and hexanoate without changing metabolic parameters in men with overweight/obesity. Future randomized clinical trials should investigate whether long-term Akovita SCT supplementation can aid in the treatment or prevention of metabolic disorders. Clinical trial registration: www.ClinicalTrials.gov, identifier: NCT04662411.

Fiber mixture-specific effect on distal colonic fermentation and metabolic health in lean but not in prediabetic men.

Infusions of the short-chain fatty acid (SCFA) acetate in the distal colon improved metabolic parameters in men. Here, we hypothesized that combining rapidly and slowly fermentable fibers will enhance distal colonic acetate production and improve metabolic health. In vitro cultivation studies in a validated model of the colon were used to identify fiber mixtures that yielded high distal colonic acetate production. Subsequently, in two randomized crossover studies, lean and prediabetic overweight/obese men were included. In one study, participants received supplements of either long-chain inulin+resistant starch (INU+RS), INU or maltodextrin (PLA) the day prior to a clinical investigation day (CID). The second trial studied beta glucan+RS (BG+RS) versus BG and PLA. During each CID, breath hydrogen, indirect calorimetry, plasma metabolites/hormones were assessed during fasting and postprandial conditions. Additionally, fecal microbiota composition and SCFA were determined. In prediabetic men, INU+RS increased plasma acetate compared to INU or PLA (P < .05), but did not affect metabolic parameters. In lean men, INU+RS increased breath hydrogen and fasting plasma butyrate, which was accompanied by increased energy expenditure, carbohydrate oxidation and PYY and decreased postprandial glucose concentrations (all P < .05) compared to PLA. BG+RS increased plasma butyrate compared to PLA (P < .05) in prediabetic individuals, but did not affect other fermentation/metabolic markers in both phenotypes. Fiber-induced shifts in fecal microbiota were individual-specific and more pronounced with INU+RS versus BG+RS. Administration of INU+RS (not BG+RS) the day prior to investigation improved metabolic parameters in lean but not in prediabetic individuals, demonstrating that effects were phenotype- and fiber-specific. Further research should study whether longer-term supplementation periods are required to elicit beneficial metabolic health in prediabetic individuals. Trial registration numbers: Clinical trial No. NCT03711383 (Inulin study) and Clinical trial No. NCT03714646 (Beta glucan study).

Gut Microbiota Regulate Pancreatic Growth, Exocrine Function, and Gut Hormones.

Growing evidence indicates an important link between gut microbiota, obesity, and metabolic syndrome. Alterations in exocrine pancreatic function are also widely present in patients with diabetes and obesity. To examine this interaction, C57BL/6J mice were fed a chow diet, a high-fat diet (HFD), or an HFD plus oral vancomycin or metronidazole to modify the gut microbiome. HFD alone leads to a 40% increase in pancreas weight, decreased glucagon-like peptide 1 and peptide YY levels, and increased glucose-dependent insulinotropic peptide in the plasma. Quantitative proteomics identified 138 host proteins in fecal samples of these mice, of which 32 were significantly changed by the HFD. The most significant of these were the pancreatic enzymes. These changes in amylase and elastase were reversed by antibiotic treatment. These alterations could be reproduced by transferring gut microbiota from donor C57BL/6J mice to germ-free mice. By contrast, antibiotics had no effect on pancreatic size or exocrine function in C57BL/6J mice fed the chow diet. Further, 1 week vancomycin administration significantly increased amylase and elastase levels in obese men with prediabetes. Thus, the alterations in gut microbiota in obesity can alter pancreatic growth, exocrine function, and gut endocrine function and may contribute to the alterations observed in patients with obesity and diabetes.

Acetate Does Not Affect Palmitate Oxidation and AMPK Phosphorylation in Human Primary Skeletal Muscle Cells.

Our recent in vivo human studies showed that colonic administration of sodium acetate (SA) resulted in increased circulating acetate levels, which was accompanied by increments in whole-body fat oxidation in overweight-obese men. Since skeletal muscle has a major role in whole-body fat oxidation, we aimed to investigate effects of SA on fat oxidation and underlying mechanisms in human primary skeletal muscle cells (HSkMC). We investigated the dose (0-5 mmol/L) and time (1, 4, 20, and 24 h) effect of SA on complete and incomplete endogenous and exogenous oxidation of 14C-labeled palmitate in HSkMC derived from a lean insulin sensitive male donor. Both physiological (0.1 and 0.25 mmol/L) and supraphysiological (0.5, 1 and 5 mmol/L) concentrations of SA neither increased endogenous nor exogenous fat oxidation over time in HSkMC. In addition, no effect of SA was observed on Thr172-AMPKα phosphorylation. In conclusion, our previously observed in vivo effects of SA on whole-body fat oxidation in men may not be explained via direct effects on HSkMC fat oxidation. Nevertheless, SA-mediated effects on whole-body fat oxidation may be triggered by other mechanisms including gut-derived hormones or may occur in other metabolically active tissues.

The Relationship between Circulating Acetate and Human Insulin Resistance before and after Weight Loss in the DiOGenes Study.

Microbially-produced acetate has been reported to beneficially affect metabolic health through effects on satiety, energy expenditure, insulin sensitivity, and substrate utilization. Here, we investigate the association between sex-specific concentrations of acetate and insulin sensitivity/resistance indices (Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), circulating insulin and Matsuda Index) in the Diet, Obesity and Genes (DiOGenes) Dietary study at baseline and after a low-calorie diet (LCD, 800 kcal/d). In this analysis, 692 subjects (Body Mass Index >27 kg/m2) were included, who underwent an LCD for 8 weeks. Linear mixed models were performed, which were adjusted for mean acetate concentration, center (random factor), age, weight loss, and fat-free mass (FFM). At baseline, no associations between plasma acetate and insulin sensitivity/resistance indices were found. We found a slight positive association between changes in acetate and changes in HOMA-IR (std 0.130, p = 0.033) in women, but not in men (std -0.072, p = 0.310) independently of age, weight loss and FFM. We were not able to confirm previously reported associations between acetate and insulin sensitivity in this large European cohort. The mechanisms behind the sex-specific relationship between LCD-induced changes in acetate and insulin sensitivity require further study.

Gut microbial metabolites in obesity, NAFLD and T2DM.

Evidence is accumulating that the gut microbiome is involved in the aetiology of obesity and obesity-related complications such as nonalcoholic fatty liver disease (NAFLD), insulin resistance and type 2 diabetes mellitus (T2DM). The gut microbiota is able to ferment indigestible carbohydrates (for example, dietary fibre), thereby yielding important metabolites such as short-chain fatty acids and succinate. Numerous animal studies and a handful of human studies suggest a beneficial role of these metabolites in the prevention and treatment of obesity and its comorbidities. Interestingly, the more distal colonic microbiota primarily ferments peptides and proteins, as availability of fermentable fibre, the major energy source for the microbiota, is limited here. This proteolytic fermentation yields mainly harmful products such as ammonia, phenols and branched-chain fatty acids, which might be detrimental for host gut and metabolic health. Therefore, a switch from proteolytic to saccharolytic fermentation could be of major interest for the prevention and/or treatment of metabolic diseases. This Review focuses on the role of products derived from microbial carbohydrate and protein fermentation in relation to obesity and obesity-associated insulin resistance, T2DM and NAFLD, and discusses the mechanisms involved.

The Short-Chain Fatty Acid Acetate in Body Weight Control and Insulin Sensitivity.

The interplay of gut microbiota, host metabolism, and metabolic health has gained increased attention. Gut microbiota may play a regulatory role in gastrointestinal health, substrate metabolism, and peripheral tissues including adipose tissue, skeletal muscle, liver, and pancreas via its metabolites short-chain fatty acids (SCFA). Animal and human data demonstrated that, in particular, acetate beneficially affects host energy and substrate metabolism via secretion of the gut hormones like glucagon-like peptide-1 and peptide YY, which, thereby, affects appetite, via a reduction in whole-body lipolysis, systemic pro-inflammatory cytokine levels, and via an increase in energy expenditure and fat oxidation. Thus, potential therapies to increase gut microbial fermentation and acetate production have been under vigorous scientific scrutiny. In this review, the relevance of the colonically and systemically most abundant SCFA acetate and its effects on the previously mentioned tissues will be discussed in relation to body weight control and glucose homeostasis. We discuss in detail the differential effects of oral acetate administration (vinegar intake), colonic acetate infusions, acetogenic fiber, and acetogenic probiotic administrations as approaches to combat obesity and comorbidities. Notably, human data are scarce, which highlights the necessity for further human research to investigate acetate's role in host physiology, metabolic, and cardiovascular health.

Circulating but not faecal short-chain fatty acids are related to insulin sensitivity, lipolysis and GLP-1 concentrations in humans.

Microbial-derived short-chain fatty acids (SCFA) acetate, propionate and butyrate may provide a link between gut microbiota and whole-body insulin sensitivity (IS). In this cross-sectional study (160 participants, 64% male, BMI: 19.2-41.0 kg/m2, normal or impaired glucose metabolism), associations between SCFA (faecal and fasting circulating) and circulating metabolites, substrate oxidation and IS were investigated. In a subgroup (n = 93), IS was determined using a hyperinsulinemic-euglycemic clamp. Data were analyzed using multiple linear regression analysis adjusted for sex, age and BMI. Fasting circulating acetate, propionate and butyrate concentrations were positively associated with fasting GLP-1 concentrations. Additionally, circulating SCFA were negatively related to whole-body lipolysis (glycerol), triacylglycerols and free fatty acids levels (standardized (std) ß adjusted (adj) -0.190, P = 0.023; std ß adj -0.202, P = 0.010; std ß adj -0.306, P = 0.001, respectively). Circulating acetate and propionate were, respectively, negatively and positively correlated with IS (M-value: std ß adj -0.294, P < 0.001; std ß adj 0.161, P = 0.033, respectively). We show that circulating rather than faecal SCFA were associated with GLP-1 concentrations, whole-body lipolysis and peripheral IS in humans. Therefore, circulating SCFA are more directly linked to metabolic health, which indicates the need to measure circulating SCFA in human prebiotic/probiotic intervention studies as a biomarker/mediator of effects on host metabolism.

Gastrointestinal Transit Time, Glucose Homeostasis and Metabolic Health: Modulation by Dietary Fibers.

Gastrointestinal transit time may be an important determinant of glucose homeostasis and metabolic health through effects on nutrient absorption and microbial composition, among other mechanisms. Modulation of gastrointestinal transit may be one of the mechanisms underlying the beneficial health effects of dietary fibers. These effects include improved glucose homeostasis and a reduced risk of developing metabolic diseases such as obesity and type 2 diabetes mellitus. In this review, we first discuss the regulation of gastric emptying rate, small intestinal transit and colonic transit as well as their relation to glucose homeostasis and metabolic health. Subsequently, we briefly address the reported health effects of different dietary fibers and discuss to what extent the fiber-induced health benefits may be mediated through modulation of gastrointestinal transit.

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 ß-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 ß-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 ß-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.