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In vitro gut models allow for the study of the impact of molecules on human gut microbiota composition and function without the implication of the host. However, current models, such as the Simulator of Human Intestinal Microbial Ecosystem (SHIME®), are expensive, time-consuming, and require specialized personnel. Homemade in vitro models that lessen these issues have limited evidence of their humanlike functionality. In this study, we present the development of a low-cost and easy-to-use bioreactor with the proven functionality of human microbiota. In our model, we evaluated the capability of replicating human gut microbiota growth and the response of the human bacterial community to a prebiotic, resistant starch, particularly resistant starch type 2 (RS2). Our bioreactor produced an environment that was stable for pH, temperature, and anaerobic conditions. The bioreactor consistently cultivated bacterial communities over a 48 h time period, replicating the composition of the gut microbiota and the associated metabolite production response to RS2, in line with prior human studies. In response to the RS2 prebiotic, we observed an increase in Bifidobacterium adolescentis and Bifidobacterium faecale and an increase in the production of the short-chain fatty acids such as acetate, propionate, and isobutyrate. Taken together, these data demonstrate that our low-cost and user-friendly prototype bioreactor model provides a favorable environment for the growth of human gut microbiota and can mimic its response to a prebiotic.
RESUMEN
Metabolic-associated fatty liver disease (MAFLD) has been identified as risk factor of incident type 2 diabetes (T2D), but the underlying postprandial mechanisms remain unclear. We compared the glucose metabolism, insulin resistance, insulin secretion, and insulin clearance post-oral glucose tolerance test (OGTT) between individuals with and without MAFLD. We included 50 individuals with a body mass index (BMI) between 25 and 40 kg/m2 and ≥1 metabolic alteration: increased fasting triglycerides or insulin, plasma glucose 5.5-6.9 mmol/L, or glycated hemoglobin 5.7-5.9%. Participants were grouped according to MAFLD status, defined as hepatic fat fraction (HFF) ≥5% on MRI. We used oral minimal model on a frequently sampled 3 h 75 g-OGTT to estimate insulin sensitivity, insulin secretion, and pancreatic ß-cell function. Fifty percent of participants had MAFLD. Median age (IQR) [57 (45-65) vs. 57 (44-63) yr] and sex (60% vs. 56% female) were comparable between groups. Post-OGTT glucose concentrations did not differ between groups, whereas post-OGTT insulin concentrations were higher in the MAFLD group (P < 0.03). Individuals with MAFLD exhibited lower insulin clearance, insulin sensitivity, and first-phase pancreatic ß-cell function. In all individuals, increased insulin incremental area under the curve and decreased insulin clearance were associated with HFF after adjusting for age, sex, and BMI (P < 0.02). Among individuals with metabolic alterations, the presence of MAFLD was characterized mainly by post-OGTT hyperinsulinemia and reduced insulin clearance while exhibiting lower first phase ß-cell function and insulin sensitivity. This suggests that MAFLD is linked with impaired insulin metabolism that may precede T2D.NEW & NOTEWORTHY Using an oral glucose tolerance test, we found hyperinsulinemia, lower insulin sensitivity, lower insulin clearance, and lower first-phase pancreatic ß-cell function in individuals with MAFLD. This may explain part of the increased risk of incident type 2 diabetes in this population. These data also highlight implications of hyperinsulinemia and impaired insulin clearance in the progression of MAFLD to type 2 diabetes.
Asunto(s)
Glucemia , Prueba de Tolerancia a la Glucosa , Hiperinsulinismo , Resistencia a la Insulina , Insulina , Enfermedad del Hígado Graso no Alcohólico , Humanos , Femenino , Masculino , Persona de Mediana Edad , Hiperinsulinismo/metabolismo , Hiperinsulinismo/sangre , Anciano , Adulto , Glucemia/metabolismo , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Insulina/sangre , Insulina/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/complicaciones , Periodo Posprandial , Secreción de Insulina , Índice de Masa Corporal , Hígado/metabolismo , Células Secretoras de Insulina/metabolismoRESUMEN
Overconsumption of added sugars is now largely recognized as a major culprit in the global situation of obesity and metabolic disorders. Previous animal studies reported that maple syrup (MS) is less deleterious than refined sugars on glucose metabolism and hepatic health, but the mechanisms remain poorly studied. Beyond its content in sucrose, MS is a natural sweetener containing several bioactive compounds, such as polyphenols and inulin, which are potential gut microbiota modifiers. We aimed to investigate the impact of MS on metabolic health and gut microbiota in male C57Bl/6J mice fed a high-fat high-sucrose (HFHS + S) diet or an isocaloric HFHS diet in which a fraction (10% of the total caloric intake) of the sucrose was substituted by MS (HFHS + MS). Insulin and glucose tolerance tests were performed at 5 and 7 wk into the diet, respectively. The fecal microbiota was analyzed by whole-genome shotgun sequencing. Liver lipids and inflammation were determined, and hepatic gene expression was assessed by transcriptomic analysis. Maple syrup was less deleterious on insulin resistance and decreased liver steatosis compared with mice consuming sucrose. This could be explained by the decreased intestinal α-glucosidase activity, which is involved in carbohydrate digestion and absorption. Metagenomic shotgun sequencing analysis revealed that MS intake increased the abundance of Faecalibaculum rodentium, Romboutsia ilealis, and Lactobacillus johnsonii, which all possess gene clusters involved in carbohydrate metabolism, such as sucrose utilization and butyric acid production. Liver transcriptomic analyses revealed that the cytochrome P450 (Cyp450) epoxygenase pathway was differently modulated between HFHS + S- and HFHS + MS-fed mice. These results show that substituting sucrose for MS alleviated dysmetabolism in diet-induced obese mice, which were associated with decreased carbohydrate digestion and shifting gut microbiota.NEW & NOTEWORTHY The natural sweetener maple syrup has sparked much interest as an alternative to refined sugars. This study aimed to investigate whether the metabolic benefits of substituting sucrose with an equivalent dose of maple syrup could be linked to changes in gut microbiota composition and digestion of carbohydrates in obese mice. We demonstrated that maple syrup is less detrimental than sucrose on metabolic health and possesses a prebiotic-like activity through novel gut microbiota and liver mechanisms.
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Acer , Microbioma Gastrointestinal , Masculino , Animales , Ratones , Sacarosa , Ratones Obesos , Hígado/metabolismo , Dieta Alta en Grasa , Edulcorantes , Digestión , Ratones Endogámicos C57BLRESUMEN
OBJECTIVE: Faecal microbiota transplantation (FMT) in germ-free (GF) mice is a common approach to study the causal role of the gut microbiota in metabolic diseases. Lack of consideration of housing conditions post-FMT may contribute to study heterogeneity. We compared the impact of two housing strategies on the metabolic outcomes of GF mice colonised by gut microbiota from mice treated with a known gut modulator (cranberry proanthocyanidins (PAC)) or vehicle. DESIGN: High-fat high-sucrose diet-fed GF mice underwent FMT-PAC colonisation in sterile individual positive flow ventilated cages under rigorous housing conditions and then maintained for 8 weeks either in the gnotobiotic-axenic sector or in the specific pathogen free (SPF) sector of the same animal facility. RESULTS: Unexpectedly, 8 weeks after colonisation, we observed opposing liver phenotypes dependent on the housing environment of mice. Mice housed in the GF sector receiving the PAC gut microbiota showed a significant decrease in liver weight and hepatic triglyceride accumulation compared with control group. Conversely, exacerbated liver steatosis was observed in the FMT-PAC mice housed in the SPF sector. These phenotypic differences were associated with housing-specific profiles of colonising bacterial in the gut and of faecal metabolites. CONCLUSION: These results suggest that the housing environment in which gnotobiotic mice are maintained post-FMT strongly influences gut microbiota composition and function and can lead to distinctive phenotypes in recipient mice. Better standardisation of FMT experiments is needed to ensure reproducible and translatable results.
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Vivienda , Microbiota , Animales , Ratones , Calidad de la Vivienda , Obesidad/metabolismo , Trasplante de Microbiota Fecal , Fenotipo , Dieta Alta en Grasa/efectos adversos , Vida Libre de Gérmenes , Ratones Endogámicos C57BLRESUMEN
Interactions between host and gut microbial communities are modulated by diets and play pivotal roles in immunological homeostasis and health. We show that exchanging the protein source in a high fat, high sugar, westernized diet from casein to whole-cell lysates of the non-commensal bacterium Methylococcus capsulatus Bath is sufficient to reverse western diet-induced changes in the gut microbiota to a state resembling that of lean, low fat diet-fed mice, both under mild thermal stress (T22 °C) and at thermoneutrality (T30 °C). Concomitant with microbiota changes, mice fed the Methylococcus-based western diet exhibit improved glucose regulation, reduced body and liver fat, and diminished hepatic immune infiltration. Intake of the Methylococcu-based diet markedly boosts Parabacteroides abundances in a manner depending on adaptive immunity, and upregulates triple positive (Foxp3+RORγt+IL-17+) regulatory T cells in the small and large intestine. Collectively, these data point to the potential for leveraging the use of McB lysates to improve immunometabolic homeostasis.