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.

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.

Chitin-glucan supplementation improved postprandial metabolism and altered gut microbiota in subjects at cardiometabolic risk in a randomized trial.

Chitin-glucan (CG), an insoluble dietary fiber, has been shown to improve cardiometabolic disorders associated with obesity in mice. Its effects in healthy subjects has recently been studied, revealing its interaction with the gut microbiota. In this double-blind, randomized, cross-over, twice 3-week exploratory study, we investigated the impacts of CG on the cardiometabolic profile and gut microbiota composition and functions in 15 subjects at cardiometabolic risk. They consumed as a supplement 4.5 g of CG daily or maltodextrin as control. Before and after interventions, fasting and postprandial metabolic parameters and exhaled gases (hydrogen [H2] and methane [CH4]) were evaluated. Gut microbiota composition (16S rRNA gene sequencing analysis), fecal concentrations of bile acids, long- and short-chain fatty acids (LCFA, SCFA), zonulin, calprotectin and lipopolysaccharide binding protein (LBP) were analyzed. Compared to control, CG supplementation increased exhaled H2 following an enriched-fiber breakfast ingestion and decreased postprandial glycemia and triglyceridemia response to a standardized test meal challenge served at lunch. Of note, the decrease in postprandial glycemia was only observed in subjects with higher exhaled H2, assessed upon lactulose breath test performed at inclusion. CG decreased a family belonging to Actinobacteria phylum and increased 3 bacterial taxa: Erysipelotrichaceae UCG.003, Ruminococcaceae UCG.005 and Eubacterium ventriosum group. Fecal metabolites, inflammatory and intestinal permeability markers did not differ between groups. In conclusion, we showed that CG supplementation modified the gut microbiota composition and improved postprandial glycemic response, an early determinant of cardiometabolic risk. Our results also suggest breath H2 production as a non-invasive parameter of interest for predicting the effectiveness of dietary fiber intervention.

Fecal microbial transplantation and fiber supplementation in patients with severe obesity and metabolic syndrome: a randomized double-blind, placebo-controlled phase 2 trial.

Fecal microbial transplantation (FMT) from lean donors to patients with obesity has been associated with metabolic benefits, yet results so far have been inconsistent. In this study, we tested the application of daily fiber supplementation as an adjunct to FMT therapy to modulate cardiometabolic outcomes. We performed a double-blind randomized trial in patients with severe obesity and metabolic syndrome receiving oral FMT, to test high-fermentable (HF) and low-fermentable (LF) fiber supplements (NCT03477916). Seventy participants were randomized to the FMT-HF (n = 17), FMT-LF (n = 17), HF (n = 17) and LF (n = 19) groups. The primary outcome was the assessment of change in insulin sensitivity from baseline to 6 weeks using the homeostatic model assessment (HOMA2-IR/IS). After 6 weeks, only patients in the FMT-LF group had significant improvements in HOMA2-IR (3.16 ± 3.01 at 6 weeks versus 3.77 ± 3.57 at baseline; P = 0.02). No difference in HOMA2-IR was observed over this period for those in the FMT-HF group (3.25 ± 1.70 at 6 weeks versus 3.17 ± 1.72 at baseline; P = 0.8), the HF group (3.49 ± 1.43 at 6 weeks versus 3.26 ± 1.33 at baseline; P = 0.8) or the LF group (3.76 ± 2.01 at 6 weeks versus 3.56 ± 1.81 at baseline; P = 0.8). Interventions were safe and well-tolerated with no treatment-attributed serious adverse events. We provide proof of concept for the use of a single-dose oral FMT combined with daily low-fermentable fiber supplementation to improve insulin sensitivity in patients with severe obesity and metabolic syndrome.

Metabolite profiling reveals the interaction of chitin-glucan with the gut microbiota.

Dietary fibers are considered beneficial nutrients for health. Current data suggest that their interaction with the gut microbiota largely contributes to their physiological effects. In this context, chitin-glucan (CG) improves metabolic disorders associated with obesity in mice, but its effect on gut microbiota has never been evaluated in humans. This study explores the effect of a 3-week intervention with CG supplementation in healthy individuals on gut microbiota composition and bacterial metabolites. CG was given to healthy volunteers (n = 15) for three weeks as a supplement (4.5 g/day). Food diary, visual analog and Bristol stool form scales and a "quality of life" survey were analyzed. Among gut microbiota-derived metabolites, bile acids (BA), long- and short-chain fatty acids (LCFA, SCFA) profiling were assessed in stool samples. The gut microbiota (primary outcome) was analyzed by Illumina sequencing. A 3-week supplementation with CG is well tolerated in healthy humans. CG induces specific changes in the gut microbiota composition, with Eubacterium, Dorea and Roseburia genera showing the strongest regulation. In addition, CG increased bacterial metabolites in feces including butyric, iso-valeric, caproic and vaccenic acids. No major changes were observed for the fecal BA profile following CG intervention. In summary, our work reveals new potential bacterial genera and gut microbiota-derived metabolites characterizing the interaction between an insoluble dietary fiber -CG- and the gut microbiota.

Precision Microbiome Modulation with Discrete Dietary Fiber Structures Directs Short-Chain Fatty Acid Production.

Dietary fibers (DFs) impact the gut microbiome in ways often considered beneficial. However, it is unknown if precise and predictable manipulations of the gut microbiota, and especially its metabolic activity, can be achieved through DFs with discrete chemical structures. Using a dose-response trial with three type-IV resistant starches (RS4s) in healthy humans, we found that crystalline and phosphate cross-linked starch structures induce divergent and highly specific effects on microbiome composition that are linked to directed shifts in the output of either propionate or butyrate. The dominant RS4-induced effects were remarkably consistent within treatment groups, dose-dependent plateauing at 35 g/day, and can be explained by substrate-specific binding and utilization of the RS4s by bacterial taxa with different pathways for starch metabolism. Overall, these findings support the potential of using discrete DF structures to achieve targeted manipulations of the gut microbiome and its metabolic functions relevant to health.

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.

Inulin-type fructans improve active ulcerative colitis associated with microbiota changes and increased short-chain fatty acids levels.

The intestinal microbiota is involved in ulcerative colitis (UC) pathogenesis. Prebiotics are hypothesized to improve health through alterations to gut microbiota composition and/or activity. Our aim was therefore to determine if inulin-type fructans induce clinical benefits in UC, and identify if benefits are linked to compositional and/or functional shifts of the luminal (fecal) and mucosal (biopsy) bacterial communities. Patients (n = 25) with mild/moderately active UC received 7.5 g (n = 12) or 15 g (n = 13) daily oral oligofructose-enriched inulin (Orafti®Synergy1) for 9 weeks. Total Mayo score, endoscopic activity and fecal calprotectin were assessed. Fecal and mucosal bacterial communities were characterized by 16S rRNA tag sequencing, and short chain fatty acids (SCFA) production were measured in fecal samples. Fructans significantly reduced colitis in the high-dose group, with 77% of patients showing a clinical response versus 33% in the low-dose group (P = 0.04). Fructans increased colonic butyrate production in the 15 g/d dose, and fecal butyrate levels were negatively correlated with Mayo score (r = -0.50; P = 0.036). The high fructan dose led to an increased Bifidobacteriaceae and Lachnospiraceae abundance but these shifts were not correlated with improved disease scores. In summary, this pilot study revealed that 15 g/d dose inulin type fructans in UC produced functional but not compositional shifts of the gut microbiota, suggesting that prebiotic-induced alterations of gut microbiota metabolism are more important than compositional changes for the benefits in UC. The findings warrant future well-powered controlled studies for the use of ß-fructans as adjunct therapy in patients with active UC.

Dietary non-fermentable fiber prevents autoimmune neurological disease by changing gut metabolic and immune status.

The autoimmune neurological disease, Multiple Sclerosis (MS), have increased at alarming rates in the Western society over the last few decades. While there are numerous efforts to develop novel treatment approaches, there is an unmet need to identify preventive strategies. We explored whether central nervous system (CNS) autoimmunity can be prevented through dietary manipulation using a spontaneous autoimmune encephalomyelitis mouse model. We report that the nutritional supplementation of non-fermentable fiber, common components of a vegetarian diet, in early adult life, prevents autoimmune disease. Dietary non-fermentable fiber alters the composition of the gut microbiota and metabolic profile with an increase in the abundance of long-chain fatty acids. Immune assays revealed that cecal extracts and a long chain fatty acid but not cecal lysates promoted autoimmune suppressive TH2 immune responses, demonstrating that non-fermentable fiber-induced metabolic changes account for the beneficial effects. Overall, these findings identify a non-invasive dietary strategy to prevent CNS autoimmunity and warrants a focus on nutritional approaches in human MS.

No. 358-Intravaginal Laser for Genitourinary Syndrome of Menopause and Stress Urinary Incontinence.

OBJECTIVE: This technical bulletin reviews the evidence relating to risks and benefits of using intravaginal laser technology in the management of genitourinary syndrome of menopause and stress urinary incontinence. INTENDED USERS: Gynaecologists, urogynaecologists, urologists, and other health care professionals who assess, counsel, and provide care for women with genitourinary syndrome of menopause and stress urinary incontinence. TARGET POPULATION: Adult women with genitourinary syndrome of menopause and stress urinary incontinence seeking complementary or alternative treatment options to topical estrogen, non-hormonal vaginal moisturizers, physiotherapy, intravaginal devices, and surgery. OPTIONS: The discussion relates to intravaginal laser treatments for genitourinary syndrome of menopause compared with topical estrogen and that for stress urinary incontinence. OUTCOMES: The outcomes of interest are objective and subjective rates of response to treatment, histologic outcomes, and procedural complications. EVIDENCE: PubMed, Medline, the Cochrane Database, and EMBASE were searched using the key words "genitourinary syndrome of menopause," "vaginal laser," "topical estrogen," and "urogenital atrophy." Results were restricted to English and human research. Articles were included until the end of September 2016. Clinical practice guidelines and guidelines of specialty societies were reviewed. Included studies were observational or prospective cohort when available. Only publications with study groups larger than or equal to 20 individuals were included, and non-peer-reviewed papers were excluded. VALIDATION METHODS: The content and recommendations were drafted and agreed upon by the principal authors. The Board of the SOGC approved the final draft for publication. The quality of evidence was rated using the criteria described in the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology framework. BENEFITS, HARMS, AND/OR COSTS: It is expected that this technical bulletin will benefit patients with genitourinary syndrome of menopause by ensuring treating physicians are aware of all treatment options including the potential benefit and associated risk with intravaginal laser therapy. This should guide patient informed consent before such procedures are undertaken. There are no direct harms or costs identified with the implementation of this guideline. SPONSORS: The SOGC. SUMMARY STATEMENTS: RECOMMENDATIONS.

Resilience of small intestinal beneficial bacteria to the toxicity of soybean oil fatty acids.

Over the past century, soybean oil (SBO) consumption in the United States increased dramatically. The main SBO fatty acid, linoleic acid (18:2), inhibits in vitro the growth of lactobacilli, beneficial members of the small intestinal microbiota. Human-associated lactobacilli have declined in prevalence in Western microbiomes, but how dietary changes may have impacted their ecology is unclear. Here, we compared the in vitro and in vivo effects of 18:2 on Lactobacillus reuteri and L. johnsonii. Directed evolution in vitro in both species led to strong 18:2 resistance with mutations in genes for lipid biosynthesis, acid stress, and the cell membrane or wall. Small-intestinal Lactobacillus populations in mice were unaffected by chronic and acute 18:2 exposure, yet harbored both 18:2- sensitive and resistant strains. This work shows that extant small intestinal lactobacilli are protected from toxic dietary components via the gut environment as well as their own capacity to evolve resistance.

Ability of the gut microbiota to produce PUFA-derived bacterial metabolites: Proof of concept in germ-free versus conventionalized mice.

SCOPE: The gut microbiota is able to modulate host physiology through the production of bioactive metabolites. Our recent studies suggest that changes in gut microbiota composition upon prebiotics supplementation alter tissue levels of PUFA-derived metabolites in mice. However, in vivo evidence that gut microbes produces PUFA-derived metabolites is lacking. This study aimed to decipher the contribution of gut microbes versus that of the host in PUFA-derived metabolite production. METHODS AND RESULTS: To achieve this goal, we compared the proportion of PUFA-derived metabolites and the expression of fatty acid desaturases in germ-free (GF) and conventionalized (CONV) mice fed either a low fat or Western diet. Higher concentrations of PUFA-derived metabolites were found in the colonic contents of conventionalized mice (CONV) mice compared to GF mice. The abundance of these metabolites in host tissues was modulated by dietary treatments but not by microbial status. Although microbial status did significantly influence desaturase expression, no correlations between host enzymes and tissue PUFA-derived metabolite levels were observed. CONCLUSION: Together, these results highlight the ability of the gut microbiota to produce PUFA-derived metabolites from dietary PUFA. However, microbial production of these metabolites in colonic contents is not necessarily associated with modifications of their concentration in host tissues.

Dietary selenium affects host selenoproteome expression by influencing the gut microbiota.

Colonization of the gastrointestinal tract and composition of the microbiota may be influenced by components of the diet, including trace elements. To understand how selenium regulates the intestinal microflora, we used high-throughput sequencing to examine the composition of gut microbiota of mice maintained on selenium-deficient, selenium-sufficient, and selenium-enriched diets. The microbiota diversity increased as a result of selenium in the diet. Specific phylotypes showed differential effects of selenium, even within a genus, implying that selenium had unique effects across microbial taxa. Conventionalized germ-free mice subjected to selenium diets gave similar results and showed an increased diversity of the bacterial population in animals fed with higher levels of selenium. Germ-free mice fed selenium diets modified their selenoproteome expression similar to control mice but showed higher levels and activity of glutathione peroxidase 1 and methionine-R-sulfoxide reductase 1 in the liver, suggesting partial sequestration of selenium by the gut microorganisms, limiting its availability for the host. These changes in the selenium status were independent of the levels of other trace elements. The data show that dietary selenium affects both composition of the intestinal microflora and colonization of the gastrointestinal tract, which, in turn, influence the host selenium status and selenoproteome expression.

Depletion of luminal iron alters the gut microbiota and prevents Crohn's disease-like ileitis.

BACKGROUND: Iron replacement therapy is a common treatment in patients with anaemia and Crohn's disease, but oral iron supplements are less tolerated. The pathogenesis of Crohn's disease is attributed to intestinal bacteria and environmental factors that trigger disease in a genetically predisposed host. The aim of this study was to characterise the interrelationship between luminal iron sulfate, systemic iron, the gut microbiota and the development of chronic ileitis in a murine model of Crohn's disease. METHODS: Wild type (WT) and heterozygous TNF(ΔARE/WT) mice were fed with an iron sulfate containing or iron sulfate free diet in combination with intraperitoneal control injections or iron injections for 11 weeks. RESULTS: TNF(ΔARE/WT) mice develop severe inflammation of the distal ileum but remained completely healthy when transferred to an iron sulfate free diet, even if iron was systemically repleted. Absence of luminal iron sulfate reduced cellular markers of endoplasmic reticulum (ER) stress responses and pro-apoptotic mechanisms in the ileal epithelium. Phenotype or reactivity of major effector intraepithelial CD8αß(+) T cells were not altered in the absence of luminal iron. Interestingly, ER stress mechanisms sensitised the small intestinal epithelial cell (IEC) line Mode-K to cytotoxic function of effector T cells from TNF(ARE/WT) mice. Pyrosequencing of 16S rRNA tags of the caecal microbiota revealed that depletion of luminal iron sulfate induced significant compositional alterations, while total microbial diversity (Shannon's diversity index) and number of total operational taxonomic units were not affected. CONCLUSION: This study showed that an iron sulfate free diet in combination with systemic iron repletion prevents the development of chronic ileitis in a murine model of Crohn's disease. Luminal iron may directly affect IEC function or generate a pathological milieu in the intestine that triggers epithelial cell stress-associated apoptosis through changes in microbial homeostasis. These results suggest that oral replacement therapy with iron sulfate may trigger inflammatory processes associated with progression of Crohn's disease-like ileitis.

Diet-induced metabolic improvements in a hamster model of hypercholesterolemia are strongly linked to alterations of the gut microbiota.

The mammalian gastrointestinal microbiota exerts a strong influence on host lipid and cholesterol metabolism. In this study, we have characterized the interplay among diet, gut microbial ecology, and cholesterol metabolism in a hamster model of hypercholesterolemia. Previous work in this model had shown that grain sorghum lipid extract (GSL) included in the diet significantly improved the high-density lipoprotein (HDL)/non-HDL cholesterol equilibrium (T. P. Carr, C. L. Weller, V. L. Schlegel, S. L. Cuppett, D. M. Guderian, Jr., and K. R. Johnson, J. Nutr. 135:2236-2240, 2005). Molecular analysis of the hamsters' fecal bacterial populations by pyrosequencing of 16S rRNA tags, PCR-denaturing gradient gel electrophoresis, and Bifidobacterium-specific quantitative real-time PCR revealed that the improvements in cholesterol homeostasis induced through feeding the hamsters GSL were strongly associated with alterations of the gut microbiota. Bifidobacteria, which significantly increased in abundance in hamsters fed GSL, showed a strong positive association with HDL plasma cholesterol levels (r = 0.75; P = 0.001). The proportion of members of the family Coriobacteriaceae decreased when the hamsters were fed GSL and showed a high positive association with non-HDL plasma cholesterol levels (r = 0.84; P = 0.0002). These correlations were more significant than those between daily GSL intake and animal metabolic markers, implying that the dietary effects on host cholesterol metabolism are conferred, at least in part, through an effect on the gut microbiota. This study provides evidence that modulation of the gut microbiota-host metabolic interrelationship by dietary intervention has the potential to improve mammalian cholesterol homeostasis, which has relevance for cardiovascular health.