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Syndromic and non-syndromic obesity conditions in children, such as Prader-Willi syndrome (PWS) and non-alcoholic fatty liver disease (NAFLD), both lower quality of life and increase risk for chronic health complications, which further increase health service utilization and cost. In a pilot observational study, we compared body composition and muscle strength in children aged 7−18 years with either PWS (n = 9), NAFLD (n = 14), or healthy controls (n = 16). Anthropometric and body composition measures (e.g., body weight, circumferences, skinfolds, total/segmental composition, and somatotype), handgrip strength, six minute-walk-test (6MWT), physical activity, and markers of liver and cardiometabolic dysfunction (e.g., ALT, AST, blood pressure, glucose, insulin, and lipid profile) were measured using standard procedures and validated tools. Genotyping was determined for children with PWS. Children with PWS had reduced lean body mass (total/lower limb mass), lower handgrip strength, 6MWT and increased sedentary activity compared to healthy children or those with NAFLD (p < 0.05). Children with PWS, including those of normal body weight, had somatotypes consistent with relative increased adiposity (endomorphic) and reduced skeletal muscle robustness (mesomorphic) when compared to healthy children and those with NAFLD. Somatotype characterizations were independent of serum markers of cardiometabolic dysregulation but were associated with increased prevalence of abnormal systolic and diastolic blood pressure Z-scores (p < 0.05). Reduced lean body mass and endomorphic somatotypes were associated with lower muscle strength/functionality and sedentary lifestyles, particularly in children with PWS. These findings are relevant as early detection of deficits in muscle strength and functionality can ensure effective targeted treatments that optimize physical activity and prevent complications into adulthood.
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Enfermedad del Hígado Graso no Alcohólico , Síndrome de Prader-Willi , Niño , Humanos , Adulto , Síndrome de Prader-Willi/complicaciones , Enfermedad del Hígado Graso no Alcohólico/etiología , Proyectos Piloto , Fuerza de la Mano , Calidad de Vida , Composición Corporal , Fuerza Muscular , Obesidad , Índice de Masa CorporalRESUMEN
BACKGROUND AND AIMS: Cirrhosis is associated with dysbiosis, but its functional consequences are still largely unknown. Short-chain fatty acids (SCFAs) account for physiological interactions between the gut microbiota and host. Our aim was to assess the impact of cirrhotic dysbiosis on the production of SCFAs. METHODS: Seventeen patients with cirrhosis and 17 controls were selected. Microbiota composition in faecal samples was assessed by next-generation 16S rRNA gene sequencing. SCFAs were measured with GC-MS in faecal samples and after in vitro batch fermentations using arabinoxylan, resistant starch, pectin, and lactulose as substrates. RESULTS: Among the 17 cirrhotic patients (mean age 58, eight males), six, nine and two were, respectively, Child-Pugh class A, B and C. Eleven patients were on oral antibiotics, 11 on lactulose and 13 on proton pump inhibitors. Cirrhotic patients showed marked differences in the composition and diversity of gut microbiome when compared to controls, that were more pronounced with increased severity. Stool samples from cirrhotic patients showed lower SCFAs content and reduced capacity to produce SCFAs in batch fermentations, with butyrate production being the most abnormal. These functional aberrancies were more pronounced with greater liver disease severity. Abundance of Ruminococcus faecis (in family Ruminococcaceae), Faecalicatena fissicatena and Fusicatenibacter saccharivorans (in family Lachnospiraceae) was positively correlated with the SCFAs production. CONCLUSION: Cirrhotic dysbiosis is associated with a decreased capacity to ferment non-digestible carbohydrates into SCFAs, especially into butyrate. These functional abnormalities are more pronounced as disease progresses. These results might inform the design of gut-targeted therapies for cirrhosis.
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Metabolismo de los Hidratos de Carbono , Disbiosis/metabolismo , Ácidos Grasos Volátiles/metabolismo , Microbioma Gastrointestinal , Cirrosis Hepática/microbiología , Estudios de Casos y Controles , Disbiosis/virología , Heces/microbiología , Femenino , Humanos , Cirrosis Hepática/complicaciones , Masculino , Persona de Mediana EdadRESUMEN
Obesity and metabolic syndrome represent a growing epidemic worldwide. Body weight is regulated through complex interactions between hormonal, neural and metabolic pathways and is influenced by numerous environmental factors. Imbalances between energy intake and expenditure can occur due to several factors, including alterations in eating behaviours, abnormal satiation and satiety, and low energy expenditure. The gut microbiota profoundly affects all aspects of energy homeostasis through diverse mechanisms involving effects on mucosal and systemic immune, hormonal and neural systems. The benefits of dietary fibre on metabolism and obesity have been demonstrated through mechanistic studies and clinical trials, but many questions remain as to how different fibres are best utilized in managing obesity. In this Review, we discuss the physiochemical properties of different fibres, current findings on how fibre and the gut microbiota interact to regulate body weight homeostasis, and knowledge gaps related to using dietary fibres as a complementary strategy. Precision medicine approaches that utilize baseline microbiota and clinical characteristics to predict individual responses to fibre supplementation represent a new paradigm with great potential to enhance weight management efficacy, but many challenges remain before these approaches can be fully implemented.
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Fibras de la Dieta , Microbioma Gastrointestinal , Obesidad , Fibras de la Dieta/metabolismo , Humanos , Obesidad/metabolismo , Microbioma Gastrointestinal/fisiología , Metabolismo Energético/fisiologíaRESUMEN
Dietary fiber supplements are a strategy to close the 'fiber gap' and induce targeted modulations of the gut microbiota. However, higher doses of fiber supplements cause gastrointestinal (GI) symptoms that differ among individuals. What determines these inter-individual differences is insufficiently understood. Here we analyzed findings from a six-week randomized controlled trial that evaluated GI symptoms to corn bran arabinoxylan (AX; n = 15) relative to non-fermentable microcrystalline cellulose (MCC; n = 16) at efficacious supplement doses of 25 g/day (females) or 35 g/day (males) in adults with excess weight. Self-reported flatulence, bloating, and stomach aches were evaluated weekly. Bacterial taxa involved in AX fermentation were identified by bioorthogonal non-canonical amino acid tagging. Associations between GI symptoms, fecal microbiota features, and diet history were systematically investigated. AX supplementation increased symptoms during the first three weeks relative to MCC (p < 0.05, Mann-Whitney tests), but subjects 'adapted' with symptoms reverting to baseline levels toward the end of treatment. Symptom adaptations were individualized and correlated with the relative abundance of Bifidobacterium longum at baseline (rs = 0.74, p = 0.002), within the bacterial community that utilized AX (rs = 0.69, p = 0.006), and AX-induced shifts in acetate (rs = 0.54, p = 0.039). Lower baseline consumption of animal-based foods and higher whole grains associated with less severity and better adaptation. These findings suggest that humans do 'adapt' to tolerate efficacious fiber doses, and this process is linked to their microbiome and dietary factors known to interact with gut microbes, providing a basis for the development of strategies for improved tolerance of dietary fibers.
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Bifidobacterium longum , Fibras de la Dieta , Heces , Microbioma Gastrointestinal , Xilanos , Xilanos/metabolismo , Humanos , Heces/microbiología , Heces/química , Masculino , Femenino , Fibras de la Dieta/metabolismo , Persona de Mediana Edad , Microbioma Gastrointestinal/efectos de los fármacos , Bifidobacterium longum/metabolismo , Adulto , Suplementos Dietéticos/análisis , Fermentación , Anciano , Adaptación FisiológicaRESUMEN
Given the worldwide epidemic of overweight and obesity among children, evidence-based dietary recommendations are fundamentally important for obesity prevention. Although the significance of the human gut microbiome in shaping the physiological effects of diet and obesity has been widely recognized, nutritional therapeutics for the mitigation of pediatric obesity globally are only just starting to leverage advancements in the nutritional microbiology field. In this review, we extracted data from PubMed, EMBASE, Scopus, Web of Science, Google Scholar, CNKI, Cochrane Library and Wiley online library that focuses on the characterization of gut microbiota (including bacteria, fungi, viruses, and archaea) in children with obesity. We further review host-microbe interactions as mechanisms mediating the physiological effects of dietary fibers and how fibers alter the gut microbiota in children with obesity. Contemporary nutritional recommendations for the prevention of pediatric obesity are also discussed from a gut microbiological perspective. Finally, we propose an experimental framework for integrating gut microbiota into nutritional interventions for children with obesity and provide recommendations for the design of future studies on precision nutrition for pediatric obesity.
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Fibras de la Dieta , Microbioma Gastrointestinal , Obesidad Infantil , Humanos , Fibras de la Dieta/administración & dosificación , Obesidad Infantil/prevención & control , Obesidad Infantil/microbiología , Niño , Bacterias/clasificación , Bacterias/metabolismo , Interacciones Microbiota-Huesped , DietaRESUMEN
Microbial-based therapeutics in clinical practice are of considerable interest, and a recent study demonstrated fecal microbial transplantation (FMT) followed by dietary fiber supplements improved glucose homeostasis. Previous evidence suggests that donor and recipient compatibility and FMT protocol are key determinants, but little is known about the involvement of specific recipient factors. Using data from our recent randomized placebo-control phase 2 clinical trial in adults with obesity and metabolic syndrome, we grouped participants that received FMT from one of 4 donors with either fiber supplement into HOMA-IR responders (n = 21) and HOMA-IR non-responders (n = 8). We further assessed plasma bile acids using targeted metabolomics and performed subgroup analyzes to evaluate the effects of recipient parameters and gastrointestinal factors on microbiota engraftment and homeostatic model assessment of insulin resistance (HOMA2-IR) response. The baseline fecal microbiota composition at genus level of recipients could predict the improvements in HOMA2-IR at week 6 (ROC-AUC = 0.70). Prevotella was identified as an important predictor, with responders having significantly lower relative abundance than non-responders (p = .02). In addition, recipients displayed a highly individualized degree of microbial engraftment from donors. Compared to the non-responders, the responders had significantly increased bacterial richness (Chao1) after FMT and a more consistent engraftment of donor-specific bacteria ASVs (amplicon sequence variants) such as Faecalibacillus intestinalis (ASV44), Roseburia spp. (ASV103), and Christensenellaceae spp. (ASV140) (p < .05). Microbiota engraftment was strongly associated with recipients' factors at baseline including initial gut microbial diversity, fiber and nutrient intakes, inflammatory markers, and bile acid derivative levels. This study identified that responders to FMT therapy had a higher engraftment rate in the transplantation of specific donor-specific microbes, which were strongly correlated with insulin sensitivity improvements. Further, the recipient baseline gut microbiota and related factors were identified as the determinants for responsiveness to FMT and fiber supplementation. The findings provide a basis for the development of precision microbial therapeutics for the treatment of metabolic syndrome.
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Bacterias , Ácidos y Sales Biliares , Trasplante de Microbiota Fecal , Heces , Microbioma Gastrointestinal , Síndrome Metabólico , Humanos , Síndrome Metabólico/terapia , Síndrome Metabólico/microbiología , Masculino , Femenino , Adulto , Persona de Mediana Edad , Heces/microbiología , Ácidos y Sales Biliares/metabolismo , Ácidos y Sales Biliares/sangre , Bacterias/clasificación , Bacterias/aislamiento & purificación , Bacterias/genética , Bacterias/metabolismo , Obesidad/terapia , Obesidad/microbiología , Fibras de la Dieta/administración & dosificación , Fibras de la Dieta/metabolismo , Resistencia a la Insulina , Resultado del TratamientoRESUMEN
Dietary fibers are associated with favorable gastrointestinal, immune, and metabolic health outcomes when consumed at sufficient levels. Despite the well-described benefits of dietary fibers, children and adolescents continue to fall short of daily recommended levels. This gap in fiber intake (i.e., "fiber gap") might increase the risk of developing early-onset pediatric obesity and obesity-related comorbidities such as type 2 diabetes mellitus into adulthood. The structure-dependent physicochemical properties of dietary fiber are diverse. Differences in solubility, viscosity, water-holding capacity, binding capability, bulking effect, and fermentability influence the physiological effects of dietary fibers that aid in regulating appetite, glycemic and lipidemic responses, and inflammation. Of growing interest is the fermentation of fibers by the gut microbiota, which yields both beneficial and less favorable end-products such as short-chain fatty acids (e.g., acetate, propionate, and butyrate) that impart metabolic and immunomodulatory properties, and gases (e.g., hydrogen, carbon dioxide, and methane) that cause gastrointestinal symptoms, respectively. This narrative review summarizes (1) the implications of fibers on the gut microbiota and the pathophysiology of pediatric obesity, (2) some factors that potentially contribute to the fiber gap with an emphasis on undesirable gastrointestinal symptoms, (3) some methods to alleviate fiber-induced symptoms, and (4) the therapeutic potential of whole foods and commonly marketed fiber supplements for improved health in pediatric obesity.
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Fibras de la Dieta , Microbioma Gastrointestinal , Obesidad Infantil , Humanos , Fibras de la Dieta/farmacología , Niño , Microbioma Gastrointestinal/fisiología , AdolescenteRESUMEN
INTRODUCTION: Auricularia auricula is a well-known traditional edible and medical fungus with high nutritional and pharmacological values, as well as metabolic and immunoregulatory properties. Nondigestible fermentable polysaccharides are identified as primary bioactive constituents of Auricularia auricula extracts. However, the exact mechanisms underlying the effects of Auricularia auricula polysaccharides (AAP) on obesity and related metabolic endpoints, including the role of the gut microbiota, remain insufficiently understood. METHODS: The effects of AAP on obesity were assessed within high-fat diet (HFD)-based mice through obesity trait analysis and metabolomic profiling. To determine the mechanistic role of the gut microbiota in observed anti-obesogenic effects AAP, faecal microbiota transplantation (FMT) and pseudo-germ-free mice model treated with antibiotics were also applied, together with 16S rRNA genomic-derived taxonomic profiling. RESULTS: High-fat diet (HFD) murine exposure to AAP thwarted weight gains, reduced fat depositing and enhanced glucose tolerance, together with upregulating thermogenesis proteomic biomarkers within adipose tissue. Serum metabolome indicated these effects were associated with changes in fatty acid metabolism. Intestine-dwelling microbial population assessments discovered that AAP selectively enhanced Papillibacter cinnamivorans, a commensal bacterium with reduced presence in HFD mice. Notably, HFD mice treated with oral formulations of P. cinnamivorans attenuated obesity, which was linked to decreased intestinal lipid transportation and hepatic thermogenesis. Mechanistically, it was demonstrated that P. cinnamivorans regulated intestinal lipids metabolism and liver thermogenesis by reducing the proinflammatory response and gut permeability in a JAK-STAT signaling-related manner. CONCLUSION: Datasets from the present study show that AAP thwarted dietary-driven obesity and metabolism-based disorders by regulating intestinal lipid transportation, a mechanism that is dependent on the gut commensal P. cinnamivorans. These results indicated AAP and P. cinnamivorans as newly identified pre- and probiotics that could serve as novel therapeutics against obesity.
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Obesidad , Proteómica , Animales , Ratones , ARN Ribosómico 16S , Obesidad/tratamiento farmacológico , Obesidad/microbiología , Polisacáridos/farmacología , LípidosRESUMEN
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.
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Microbioma Gastrointestinal , Microbiota , Animales , Humanos , Microbioma Gastrointestinal/fisiología , Dieta , Nutrientes , Metabolismo Energético/fisiologíaRESUMEN
The ecology driving the remodeling of gut microbial consortia with dietary fiber intervention remains incomplete. We investigated the short-term dynamics of the gut microbiota and metabolic function during inulin fermentation with distinct microbiota from two swine breeds using an in vitro fermentation model. Different gut microbiota at a transient temporal time displayed a similar response to inulin intervention such as the similar fermentation stage and a rapid response followed by gradual stabilization of microbial diversity. Inulin-induced bacterial succession and individual metabolic change were determined by the original microbial compositions, in particular the α-diversity. Levels of short-chain fatty acids (SCFAs) were predictable with the key bacteria by the regression model, especially butyrate was associated with the abundance and ecological interactions of Lactobacillus delbrueckii, Bifidobacterium thermophilum and Megasphaera elsdenii. This study emphasizes the importance of complex ecology to understand fiber-induced microbiome and metabolic changes, thus providing a reference for predictable dietary responses.
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Inulina , Microbiota , Animales , Bacterias/metabolismo , Butiratos/metabolismo , Fibras de la Dieta/análisis , Ácidos Grasos Volátiles/metabolismo , Heces/microbiología , Fermentación , Inulina/metabolismo , PorcinosRESUMEN
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.
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Microbioma Gastrointestinal , Dieta , Dieta Saludable , Microbioma Gastrointestinal/fisiología , Humanos , Estado NutricionalRESUMEN
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.
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Microbioma Gastrointestinal , Adulto , Bacterias , Ácidos y Sales Biliares/análisis , Biomarcadores/análisis , Fibras de la Dieta , Heces/microbiología , Femenino , Microbioma Gastrointestinal/fisiología , Humanos , Complejo de Antígeno L1 de Leucocito/análisis , Complejo de Antígeno L1 de Leucocito/farmacología , Masculino , Obesidad/microbiologíaRESUMEN
The response of patients with inflammatory bowel disease (IBD) to fecal microbial transplantation (FMT) has been inconsistent possibly due to variable engraftment of donor microbiota. This failure to engraft has resulted in the use of several different strategies to attempt optimization of the recipient microbiota following FMT. The purpose of our study was to evaluate the effects of two distinct microbial strategies-antibiotic pre-treatment and repeated FMT dosing-on IBD outcomes. A systematic literature review was designed and implemented in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A medical librarian conducted comprehensive searches in MEDLINE, Embase, Scopus, Web of Science Core Collection, and Cochrane Library on 25 November 2019 and updated on 29 January 2021. Primary outcomes of interest included comparing relapse and remission rates in patients with IBD for a single FMT dose, repeated FMT dosages, and antibiotic pre-treatment groups. Twenty-eight articles (six randomized trials, 20 cohort trials, two case series) containing 976 patients were identified. Meta-analysis revealed that both repeated FMT and antibiotic pre-treatment strategies demonstrated improvements in pooled response and remission rates. These clinical improvements were associated with increases in fecal microbiota richness and α-diversity, as well as the enrichment of several short-chain fatty acid (SCFA)-producing anaerobes including Bifidobacterium, Roseburia, Lachnospiraceae, Prevotella, Ruminococcus, and Clostridium related species.
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BACKGROUND: Microbiota-accessible carbohydrates (MACs) are critical substrates for intestinal microbes; the subsequent production of SCFAs may have some potential benefits for patients with type 2 diabetes mellitus (T2DM). OBJECTIVES: We conducted a meta-analysis of randomized controlled trials (RCTs) to assess the effects of higher compared with lower MAC intakes on cardiovascular risk factors in T2DM patients and performed an umbrella review of RCTs to evaluate the evidence quality concerning existing dietary T2DM interventions. METHODS: Publications were identified by searching MEDLINE, EMBASE, and CINAHL. In the meta-analysis, random-effects models were used to calculate pooled estimates, and sensitivity analyses, meta-regression, subgroup analyses, and Egger's test were performed. For the umbrella review, we summarized pooled estimates, 95% CIs, heterogeneity, and publication bias. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) and modified NutriGrade were used to assess the quality of evidence in the meta-analysis and umbrella review, respectively. RESULTS: Forty-five RCTs with 1995 participants were included in the meta-analysis. High MAC intake significantly reduced glycated hemoglobin (HbA1c) (weighted mean difference [WMD] -0.436% [-0.556, -0.315]), fasting glucose (WMD -0.835 mmol/L [-1.048, -0.622]), total cholesterol (WMD -0.293 mmol/L [-0.397, -0.190]), triglycerides (WMD -0.118 mmol/L [-0.308, -0.058]), BMI (WMD -0.476 [-0.641, -0.312]), and systolic blood pressure (WMD -3.066 mmHg [-5.653, -0.478]), with a moderate-to-high quality of evidence, compared with low intake. Region, dose, and MAC type were key variables. The umbrella review of all dietary interventions for cardiovascular risk factors in patients with T2DM included 26 meta-analyses with 158 pooled estimates. The evidence quality of MACs, dietary fiber, high-protein diet, ω-3 (n-3), viscous fiber, vitamin D, and vitamin E intake was moderate to high. CONCLUSIONS: When compared with lower intake, increased MAC intake improved glycemic control, blood lipid, body weight, and inflammatory markers for people with T2DM. This trial was registered at PROSPERO (https://www.crd.york.ac.uk/PROSPERO/#recordDetails) as CRD42019120531.
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Diabetes Mellitus Tipo 2/dietoterapia , Carbohidratos de la Dieta/metabolismo , Microbioma Gastrointestinal/fisiología , Humanos , Factores de RiesgoRESUMEN
The emerging role of a microbiota-gut-brain axis in autism spectrum disorder (ASD) suggests that modulating gut microbial composition may offer a tractable approach to addressing the lifelong challenges of ASD. The aim of this systematic review was to provide an overview and critically evaluate the current evidence on the efficacy and safety of probiotic, prebiotic, synbiotic, and fecal microbiota transplantation therapies for core and co-occurring behavioral symptoms in individuals with ASD. Comprehensive searches of MEDLINE, EMBASE, Scopus, Web of Science Core Collection, Cochrane Library, and Google Scholar were performed from inception to March 5, 2020, and two update searches were completed on October 25, 2020, and April 22, 2021, respectively. A total of 4306 publications were identified, of which 14 articles met the inclusion criteria. Data were extracted independently by two reviewers using a preconstructed form. Results of probiotic studies do not confirm the supposed beneficial effect of probiotics on ASD, whereas prebiotics and synbiotic combinations appear to be efficacious in selective behavioral symptoms. Evidence of the efficacy of fecal microbiota transplantation in ASD is still scarce but supports further research. Overall, the current evidence base to suggest beneficial effects of these modalities in ASD is limited and inconclusive. More clinical trials are currently looking at the use of microbial-based therapies in ASD. With a robust double-blind randomized controlled protocol to investigate the efficacy, these trials should provide significant and definitive results. LAY SUMMARY: There is a link between altered gut bacteria and autism spectrum disorder. Some people believe that modulating bacterial composition in the gut may help reduce autism symptoms, but evidence from human studies suggesting beneficial effects of probiotic, prebiotic, and combination thereof as well as fecal transplants in autism spectrum disorder is limited and inconclusive. Current data should not encourage use of these modalities. Further clinical studies are needed.
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Trastorno del Espectro Autista , Microbioma Gastrointestinal , Probióticos , Simbióticos , Trastorno del Espectro Autista/terapia , Síntomas Conductuales , Trasplante de Microbiota Fecal , Humanos , Prebióticos , Probióticos/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
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.
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Fibras de la Dieta/uso terapéutico , Trasplante de Microbiota Fecal/métodos , Resistencia a la Insulina/fisiología , Síndrome Metabólico/terapia , Obesidad Mórbida/terapia , Suplementos Dietéticos , Método Doble Ciego , Femenino , Fermentación/fisiología , Microbioma Gastrointestinal/fisiología , Humanos , Masculino , Persona de Mediana Edad , Prueba de Estudio ConceptualRESUMEN
The gut microbiome is hypothesized to play a crucial role in the development of obesity and insulin resistance (IR); the pathways linking the microbiome to IR in pediatrics have yet to be precisely characterized. We aimed to determine the relationship between the gut microbiome composition and metabolic functions and IR in children with obesity. In a cross-sectional study, fecal samples from children with obesity (10-16 years old) were collected for taxonomical and functional analysis of the fecal microbiome using shotgun metagenomics. The homeostatic model assessment for insulin resistance (HOMA-IR) was determined using fasting glucose and insulin. Associations between HOMA-IR and α-diversity measures as well as metabolic pathways were evaluated using Spearman correlations; relationships between HOMA-IR and ß-diversity were assessed by permutational multivariate analysis of variance. Twenty-one children (nine males; median: age = 12.0 years; BMI z-score = 2.9; HOMA-IR = 3.6) completed the study. HOMA-IR was significantly associated with measures of α-diversity but not with ß-diversity. Children with higher HOMA-IR exhibited lower overall species richness, Firmicutes species richness, and overall Proteobacteria species Shannon diversity. Furthermore, HOMA-IR was inversely correlated with the abundance of pathways related to the biosynthesis of lipopolysaccharides, amino acids, and short-chain fatty acids, whereas positive correlations between HOMA-IR and the peptidoglycan biosynthesis pathways were observed. In conclusion, insulin resistance was associated with decreased microbial α-diversity measures and abundance of genes related to the metabolic pathways. Our study provides a framework for understanding the microbial alterations in pediatric obesity.
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BACKGROUND: Accumulating evidence suggests that the metabolic effects of metformin and fermentable fibers are mediated, in part, through diverging or overlapping effects on the composition and metabolic functions of the gut microbiome. Pre-clinical animal models have established that the addition of fiber to metformin monotherapy improves glucose tolerance. However, possible synergistic effects of combination therapy (metformin plus fiber) have not been investigated in humans. Moreover, the underlying mechanisms of synergy have yet to be elucidated. The aim of this study is to compare in adolescents with obesity the metabolic effects of metformin and fermentable fibers in combination with those of metformin or fiber alone. We will also determine if therapeutic responses correlate with compositional and functional features of the gut microbiome. METHODS: This is a parallel three-armed, double-blinded, randomized controlled trial. Adolescents (aged 12-18 years) with obesity, insulin resistance (IR), and a family history of type 2 diabetes mellitus (T2DM) will receive either metformin (850 mg p.o. twice/day), fermentable fibers (35 g/day), or a combination of metformin plus fiber for 12 months. Participants will be seen at baseline, 3, 6, and 12 months, with a phone follow-up at 1 and 9 months. Primary and secondary outcomes will be assessed at baseline, 6, and 12 months. The primary outcome is change in IR estimated by homeostatic model assessment of IR; key secondary outcomes include changes in the Matsuda index, oral disposition index, body mass index z-score, and fat mass to fat-free mass ratio. To gain mechanistic insight, endpoints that reflect host-microbiota interactions will also be assessed: obesity-related immune, metabolic, and satiety markers; humoral metabolites; and fecal microbiota composition, short-chain fatty acids, and bile acids. DISCUSSION: This study will compare the potential metabolic benefits of fiber with those of metformin in adolescents with obesity, determine if metformin and fiber act synergistically to improve IR, and elucidate whether the metabolic benefits of metformin and fiber associate with changes in fecal microbiota composition and the output of health-related metabolites. This study will provide insight into the potential role of the gut microbiome as a target for enhancing the therapeutic efficacy of emerging treatments for T2DM prevention. TRIAL REGISTRATION: ClinicalTrials.gov NCT04578652 . Registered on 8 October 2020.
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Diabetes Mellitus Tipo 2 , Resistencia a la Insulina , Metformina , Obesidad Mórbida , Adolescente , Método Doble Ciego , Humanos , Hipoglucemiantes/efectos adversos , Metformina/efectos adversos , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
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.
Asunto(s)
Biomarcadores/sangre , Fibras de la Dieta/administración & dosificación , Enfermedades Metabólicas/sangre , Glucemia/análisis , Proteína C-Reactiva/análisis , Colesterol/sangre , Ensayos Clínicos como Asunto , Fibras de la Dieta/análisis , Suplementos Dietéticos , Humanos , Insulina/sangre , Resistencia a la Insulina , Lípidos/sangre , Proyectos Piloto , PlacebosRESUMEN
BACKGROUND AND AIMS: Crohn's disease [CD] is associated with alterations in gut microbial composition and function. The present controlled-intervention study investigated the relationship between patterns of dietary intake and baseline gut microbiota in CD patients in remission and examined the effects of a dietary intervention in patients consuming a non-diversified diet [NDD]. METHODS: Forty outpatients with quiescent CD were recruited in Calgary, Alberta, Canada. Based on 3-day food records, patients consuming a lower plant-based and higher red and processed meat-based diet were assigned to the NDD group [nâ =â 15] and received a 12-week structured dietary intervention; all other patients were assigned to the diversified diet [DD] control group [nâ =â 25] and received conventional management. Faecal microbiota composition, short chain fatty acids [SCFAs] and calprotectin were measured. RESULTS: At baseline the NDD and DD groups had a different faecal microbial beta-diversity [pâ =â 0.003, permutational multivariate analysis of variance]. The NDD group had lower Faecalibacterium and higher Escherichia/Shigella relative abundances compared to the DD group [3.3â ±â 5.4% vs. 8.5â ±â 10.6%; 6.9â ±â 12.2% vs. 1.6â ±â 4.4%; pâ ≤â 0.03, analysis of covariance]. These two genera showed a strong negative correlation [rs = -0.60, qâ =â 0.0002]. Faecal butyrate showed a positive correlation with Faecalibacterium [rs = 0.52, qâ =â 0.002], and an inhibitory relationship with Escherichia/Shigella abundance [four-parameter sigmoidal model, R = -0.83; rs = -0.44, qâ =â 0.01], respectively. After the 12 weeks of dietary intervention, no difference in microbial beta-diversity between the two groups was observed [pâ =â 0.43]. The NDD group demonstrated an increase in Faecalibacterium [pâ <â 0.05, generalized estimated equation model], and resembled the DD group at the end of the intervention [pâ =â 0.84, t-test with permutation]. We did not find an association of diet with faecal SCFAs or calprotectin. CONCLUSIONS: Dietary patterns are associated with specific gut microbial compositions in CD patients in remission. A diet intervention in patients consuming a NDD modifies gut microbial composition to resemble that seen in patients consuming a DD. These results show that diet is important in shaping the microbial dysbiosis signature in CD towards a balanced community.