Impact of a Powdered Meal Replacement on Metabolism and Gut Microbiota (PREMIUM) in individuals with excessive body weight: a study protocol for a randomised controlled trial.

INTRODUCTION: Excess body weight is associated with a state of low-grade chronic inflammation and alterations of the gut microbiome. Powdered meal replacements (PMR) have been shown to be an effective strategy for weight management; however, their effect on inflammation and the gut microbiome remains unclear. The aim of this 12-week randomised control clinical trial is to investigate the effects of PMR consumption, here given as a soy-yoghurt-honey formula, on inflammation, gut microbiome and overall metabolism in individuals with excessive body weight. METHODS AND ANALYSIS: Healthy adults with excess body weight (n=88) are being recruited and randomly assigned to one of the following groups: (1) Control group (CON): maintaining usual diet for 12 weeks, or (2) PMR group: replacing morning and afternoon snacks daily with a PMR for 12 weeks. Participants are asked to maintain body weight throughout the study and fill out a journal with information about PMR consumption, body weight, food intake, appetite sensations and medications. Three study visits are required: baseline, week 6 and week 12. Outcome measures include systemic inflammatory biomarkers, gut microbiome composition, metabolic blood markers, host energy metabolism, body composition, appetite sensations and host gene expression profile. ETHICS AND DISSEMINATION: This research protocol was approved by the University of Alberta Ethics Board (Pro00070712) and adheres to the Canadian Tri-Council Policy statement on the use of human participants in research. Procedures and potential risks are fully discussed with participants. Study findings will be disseminated in peer-reviewed journals, conference presentations and social media. TRIAL REGISTRATION NUMBER: NCT03235804.

Exploring the Influence of Gut Microbiome on Energy Metabolism in Humans.

The gut microbiome has a profound influence on host physiology, including energy metabolism, which is the process by which energy from nutrients is transformed into other forms of energy to be used by the body. However, mechanistic evidence for how the microbiome influences energy metabolism is derived from animal models. In this narrative review, we included human studies investigating the relationship between gut microbiome and energy metabolism -i.e., energy expenditure in humans and energy harvest by the gut microbiome. Studies have found no consistent gut microbiome patterns associated with energy metabolism, and most interventions were not effective in modulating the gut microbiome to influence energy metabolism. To date, cause-and-effect relationships and mechanistic evidence on the impact of the gut microbiome on energy expenditure have not been established in humans. Future longitudinal observational studies and randomized controlled trials utilizing robust methodologies and advanced statistical analysis are needed. Such knowledge would potentially inform the design of therapeutic avenues and specific dietary recommendations to improve energy metabolism through gut microbiome modulation.

The separate effects of whole oats and isolated beta-glucan on lipid profile: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND & AIMS: It is well known that dietary fiber positively impacts the microbiome and health as a whole. However, the health effects of ß-glucan, a dietary fiber extracted from oats, have been questioned when administered alone or incorporated into other foods. The purpose of this systematic review and meta-analysis was to evaluate the impact of oats or ß-glucan supplements on the lipid profile. METHODS: Randomized controlled trials with parallel-arm or crossover blinded interventions at least two weeks in duration, for hyperlipidemic or non-hyperlipidemic men and women ≥18 years of age were selected. Only single (participants blinded) or double-blinded studies that compared oat or isolated ß-glucan with a placebo/control group were considered for this review. The databases EMBASE, PubMed, Web of science and CINHAL were searched, from the earliest indexed year available online to the end of January 2022. Random-effects models were used to combine the estimated effects extracted from individual studies, and data were summarized as standardized mean difference (SMD) and 95% confidence interval (95%CI). RESULTS: A total of 811 articles were screened for eligibility, and relevant data were extracted from 28 studies, totaling 1494 subjects. Oat interventions TC (-0.61, 95%CI: -0.84;-0.39, p < 0.00001, and -0.70, 95%CI: -1.07;-0.34, p = 0.0002, respectively) and LDL (-0.51, 95%CI: -0.71;-0.31, p < 0.00001, and -0.38, 95%CI: -0.60;-0.15, p = 0.001, respectively). Moreover, isolated ß-glucan interventions from parallel-arm studies decreased TC (-0.73, 95%CI: -1.01;-0.45, p < 0.00001), LDL (-0.58, 95%CI: -0.85;-0.32, p < 0.0001) and triglycerides (-0.30, 95%CI: -0.49;-0.12, p = 0.001). HDL was not altered by either oat or isolated ß-glucan (p > 0.05). CONCLUSION: Overall, this review showed that both oat and isolated ß-glucan interventions improved lipid profiles. Furthermore, the ingestion of oats or isolated ß-glucan supplements are effective tools to combat dyslipidemia and should be considered in cardiovascular disease prevention.

Rethinking healthy eating in light of the gut microbiome.

Given the worldwide epidemic of diet-related chronic diseases, evidence-based dietary recommendations are fundamentally important for health promotion. Despite the importance of the human gut microbiota for the physiological effects of diet and chronic disease etiology, national dietary guidelines around the world are just beginning to capitalize on scientific breakthroughs in the microbiome field. In this review, we discuss contemporary nutritional recommendations from a microbiome science perspective, focusing on mechanistic evidence that established host-microbe interactions as mediators of the physiological effects of diet. We apply this knowledge to inform discussions of nutrition controversies, advance innovative dietary strategies, and propose an experimental framework that integrates the microbiome into nutrition research. The congruence of key paradigms in the nutrition and microbiome disciplines validates current recommendations in dietary guidelines, and the systematic incorporation of microbiome science into nutrition research has the potential to further improve and innovate healthy eating.

Elucidating the role of the gut microbiota in the physiological effects of dietary fiber.

BACKGROUND: Dietary fiber is an integral part of a healthy diet, but questions remain about the mechanisms that underlie effects and the causal contributions of the gut microbiota. Here, we performed a 6-week exploratory trial in adults with excess weight (BMI: 25-35 kg/m2) to compare the effects of a high-dose (females: 25 g/day; males: 35 g/day) supplement of fermentable corn bran arabinoxylan (AX; n = 15) with that of microbiota-non-accessible microcrystalline cellulose (MCC; n = 16). Obesity-related surrogate endpoints and biomarkers of host-microbiome interactions implicated in the pathophysiology of obesity (trimethylamine N-oxide, gut hormones, cytokines, and measures of intestinal barrier integrity) were assessed. We then determined whether clinical outcomes could be predicted by fecal microbiota features or mechanistic biomarkers. RESULTS: AX enhanced satiety after a meal and decreased homeostatic model assessment of insulin resistance (HOMA-IR), while MCC reduced tumor necrosis factor-α and fecal calprotectin. Machine learning models determined that effects on satiety could be predicted by fecal bacterial taxa that utilized AX, as identified by bioorthogonal non-canonical amino acid tagging. Reductions in HOMA-IR and calprotectin were associated with shifts in fecal bile acids, but correlations were negative, suggesting that the benefits of fiber may not be mediated by their effects on bile acid pools. Biomarkers of host-microbiome interactions often linked to bacterial metabolites derived from fiber fermentation (short-chain fatty acids) were not affected by AX supplementation when compared to non-accessible MCC. CONCLUSION: This study demonstrates the efficacy of purified dietary fibers when used as supplements and suggests that satietogenic effects of AX may be linked to bacterial taxa that ferment the fiber or utilize breakdown products. Other effects are likely microbiome independent. The findings provide a basis for fiber-type specific therapeutic applications and their personalization. TRIAL REGISTRATION: Clinicaltrials.gov, NCT02322112 , registered on July 3, 2015. Video Abstract.

Establishing or Exaggerating Causality for the Gut Microbiome: Lessons from Human Microbiota-Associated Rodents.

Human diseases are increasingly linked with an altered or "dysbiotic" gut microbiota, but whether such changes are causal, consequential, or bystanders to disease is, for the most part, unresolved. Human microbiota-associated (HMA) rodents have become a cornerstone of microbiome science for addressing causal relationships between altered microbiomes and host pathology. In a systematic review, we found that 95% of published studies (36/38) on HMA rodents reported a transfer of pathological phenotypes to recipient animals, and many extrapolated the findings to make causal inferences to human diseases. We posit that this exceedingly high rate of inter-species transferable pathologies is implausible and overstates the role of the gut microbiome in human disease. We advocate for a more rigorous and critical approach for inferring causality to avoid false concepts and prevent unrealistic expectations that may undermine the credibility of microbiome science and delay its translation.

The Effect of Isolated and Synthetic Dietary Fibers on Markers of Metabolic Diseases in Human Intervention Studies: A Systematic Review.

Observational studies provide strong evidence for the health benefits of dietary fiber (DF) intake; however, human intervention studies that supplement isolated and synthetic DFs have shown inconsistent results. Therefore, we conducted a systematic review to summarize the effects of DF supplementation on immunometabolic disease markers in intervention studies in healthy adults, and considered the role of DF dose, DF physicochemical properties, intervention duration, and the placebo used. Five databases were searched for studies published from 1990 to 2018 that assessed the effect of DF on immunometabolic markers. Eligible studies were those that supplemented isolated or synthetic DFs for ≥2 wk and reported baseline data to assess the effect of the placebo. In total, 77 publications were included. DF supplementation reduced total cholesterol (TC), LDL cholesterol, HOMA-IR, and insulin AUC in 36-49% of interventions. In contrast, <20% of the interventions reduced C-reactive protein (CRP), IL-6, glucose, glucose AUC, insulin, HDL cholesterol, and triglycerides. A higher proportion of interventions showed an effect if they used higher DF doses for CRP, TC, and LDL cholesterol (40-63%), viscous and mixed plant cell wall DFs for TC and LDL cholesterol (>50%), and longer intervention durations for CRP and glucose (50%). Half of the placebo-controlled studies used digestible carbohydrates as the placebo, which confounded findings for IL-6, glucose AUC, and insulin AUC. In conclusion, interventions with isolated and synthetic DFs resulted mainly in improved cholesterol concentrations and an attenuation of insulin resistance, whereas markers of dysglycemia and inflammation were largely unaffected. Although more research is needed to make reliable recommendations, a more targeted supplementation of DF with specific physicochemical properties at higher doses and for longer durations shows promise in enhancing several of its health effects.

Modulation of the Gastrointestinal Microbiome with Nondigestible Fermentable Carbohydrates To Improve Human Health.

There is a clear association between the gastrointestinal (GI) microbiome and the development of chronic noncommunicable diseases, providing a rationale for the development of strategies that target the GI microbiota to improve human health. In this article, we discuss the potential of supplementing the human diet with nondigestible fermentable carbohydrates (NDFCs) to modulate the composition, structure, diversity, and metabolic potential of the GI microbiome in an attempt to prevent or treat human disease. The current concepts by which NDFCs can be administered to humans, including prebiotics, fermentable dietary fibers, and microbiota-accessible carbohydrates, as well as the mechanisms by which these carbohydrates exert their health benefits, are discussed. Epidemiological research presents compelling evidence for the health effects of NDFCs, with clinical studies providing further support for some of these benefits. However, rigorously designed human intervention studies with well-established clinical markers and microbial endpoints are still essential to establish (i) the clinical efficiency of specific NDFCs, (ii) the causal role of the GI microbiota in these effects, (iii) the underlying mechanisms involved, and (iv) the degree by which inter-individual differences between GI microbiomes influence these effects. Such studies would provide the mechanistic understanding needed for a systematic application of NDFCs to improve human health via GI microbiota modulation while also allowing the personalization of these dietary strategies.