RESUMEN

BACKGROUND: Obesity is a serious health problem that dysregulate Renin-Angiotensin System (RAS) and intestinal microbiota. OBJECTIVE: The present study aimed to evaluate the Angiotensin-(1-7) [ANG-(1-7)] oral formulation effects on obese mice intestinal microbiota. METHODS: Mice were divided into four groups: obese and non-obese treated with ANG-(1-7) and obese and non-obese without ANG-(1-7) during four weeks. RESULTS: We observed a significant decrease in the fasting plasma glucose, total cholesterol, triglycerides, and Low-density lipoprotein levels and increased High-density lipoprotein in animals treated with ANG-(1-7). The histological analysis showed intestinal villi height reduction in mice treated with ANG-(1-7). Additionally, increased Bacteroidetes and decreased Firmicutes (increased Bacteroidetes/ Firmicutes ratio) and Enterobacter cloacae populations were observed in the High-Fat Diet + ANG-(1-7) group. Receptor toll-like 4 (TLR4) intestinal mRNA expression was reduced in the HFD+ANG-(1-7) group. Finally, the intestinal expression of the neutral amino acid transporter (B0AT1) was increased in animals treated with ANG-(1-7), indicating a possible mechanism associated with tryptophan uptake. CONCLUSION: The results of the present study suggest for the first time an interaction between oral ANG-(1-7) and intestinal microbiota modulation.

Asunto(s)

Angiotensina I/farmacología , Microbioma Gastrointestinal/efectos de los fármacos , Metaboloma/efectos de los fármacos , Obesidad/tratamiento farmacológico , Fragmentos de Péptidos/farmacología , Enzima Convertidora de Angiotensina 2/metabolismo , Animales , Glucemia/metabolismo , Colesterol/metabolismo , Biología Computacional , Dieta Alta en Grasa , Humanos , Intestinos/efectos de los fármacos , Lipoproteínas LDL/metabolismo , Masculino , Ratones , Ratones Obesos , Receptor Toll-Like 4/metabolismo , Triglicéridos/metabolismo

RESUMEN

SCOPE: Soy protein is a high-quality protein and its consumption has been associated with a reduction of serum cholesterol and triglycerides and an improvement in insulin resistance. However, it is not known whether the effects of soy protein are mediated by the gut microbiota. Thus, the aim of this study is to assess whether using antibiotics to partially eradicate the gut microbiota can prevent the beneficial effects of soy protein in rats. METHODS AND RESULTS: Thus, rats are fed one of the following diets for 16 weeks: casein control, soy protein control, high-fat casein, and high-fat soy protein. The rats are then treated for 4 weeks with antibiotics. Body weight and composition, energy expenditure, glucose tolerance test, metabolic endotoxemia, and gut microbiota are measured before and after treatment with antibiotic. The results show that soy protein consumption decreases weight gain, body fat, metabolic endotoxemia, and increases energy expenditure and glucose tolerance. Antibiotic treatment suppresses all these metabolic effects. These changes are accompanied by modifying the diversity and taxonomy of the gut microbiota. CONCLUSION: In conclusion, the evidence suggests that the health benefits of soy protein are partly dependent of the gut microbiota.

Asunto(s)

Antibacterianos/farmacología , Microbioma Gastrointestinal/efectos de los fármacos , Proteínas de Soja/farmacología , Tejido Adiposo/efectos de los fármacos , Ampicilina/efectos adversos , Ampicilina/farmacología , Animales , Antibacterianos/efectos adversos , Biomarcadores/metabolismo , Composición Corporal/efectos de los fármacos , Caseínas/farmacología , Dieta Alta en Grasa/efectos adversos , Endotoxemia/inducido químicamente , Metabolismo Energético/efectos de los fármacos , Ácidos Grasos Volátiles/metabolismo , Microbioma Gastrointestinal/fisiología , Inflamación/genética , Inflamación/metabolismo , Masculino , Neomicina/efectos adversos , Neomicina/farmacología , Ratas Wistar , Aumento de Peso/efectos de los fármacos

RESUMEN

Background Metabolic syndrome (MetS) is a serious health problem over the world; thus, the aim of the present work was to develop a lifestyle intervention to decrease the dysbiosis of gut microbiota and reduce the biochemical abnormalities of MetS. Methods and Results The prevalence of MetS was evaluated in 1065 subjects of Mexico City, Mexico, and the gut microbiota in a subsample. Subjects with MetS were selected for a pragmatic study based on a lifestyle intervention with a low-saturated-fat diet, reduced-energy intake, with functional foods and physical activity, and a second group was selected for a randomized control-placebo study to assess the gut microbiota after the dietary intervention. Prevalence of MetS was 53%, and the higher the body mass index, the higher the gut microbiota dysbiosis. The higher the Homeostatic Model Assessment for Insulin Resistance, the lower the high-density lipoprotein cholesterol concentration. The pragmatic study revealed that after 15 days on a low-saturated-fat diet, there was a 24% reduction in serum triglycerides; and after a 75-day lifestyle intervention, MetS was reduced by 44.8%, with a reduction in low-density lipoprotein cholesterol, small low-density lipoprotein particles, glucose intolerance, lipopolysaccharide, and branched-chain amino acid. The randomized control-placebo study showed that after the lifestyle intervention, there was a decrease in the dysbiosis of the gut microbiota associated with a reduction in the Prevotella/ Bacteroides ratio and an increase in the abundance of Akkermansia muciniphila and Faecalibacterium prausnitzii. Conclusions A lifestyle intervention significantly decreased MetS components, small low-density lipoprotein particle concentration, gut microbiota dysbiosis, and metabolic endotoxemia, reducing the risk of atherosclerosis. Clinical Trial Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT03611140.

Asunto(s)

Dieta Saludable , Endotoxemia/dietoterapia , Microbioma Gastrointestinal , Lipopolisacáridos/sangre , Lipoproteínas LDL/sangre , Síndrome Metabólico/dietoterapia , Conducta de Reducción del Riesgo , Adulto , Anciano , Biomarcadores/sangre , Restricción Calórica , Estudios Transversales , Dieta con Restricción de Grasas , Método Doble Ciego , Disbiosis , Endotoxemia/sangre , Endotoxemia/epidemiología , Endotoxemia/microbiología , Ejercicio Físico , Femenino , Alimentos Funcionales , Humanos , Masculino , Síndrome Metabólico/sangre , Síndrome Metabólico/epidemiología , Síndrome Metabólico/microbiología , México/epidemiología , Persona de Mediana Edad , Tamaño de la Partícula , Prevalencia , Factores de Tiempo , Resultado del Tratamiento , Adulto Joven

RESUMEN

Dietary fat strongly affects human health by modulating gut microbiota composition and low-grade systemic inflammation. High-fat diets have been implicated in reduced gut microbiota richness, increased Firmicutes to Bacteroidetes ratio, and several changes at family, genus and species levels. Saturated (SFA), monounsaturated (MUFA), polyunsaturated (PUFA) and conjugated linolenic fatty acids share important pathways of immune system activation/inhibition with gut microbes, modulating obesogenic and proinflammatory profiles. Mechanisms that link dietary fat, gut microbiota and obesity are mediated by increased intestinal permeability, systemic endotoxemia, and the activity of the endocannabinoid system. Although the probiotic therapy could be a complementary strategy to improve gut microbiota composition, it did not show permanent effects to treat fat-induced dysbiosis. Based upon evidence to date, we believe that high-fat diets and SFA consumption should be avoided, and MUFA and omega-3 PUFA intake should be encouraged in order to regulate gut microbiota and inflammation, promoting body weight/fat control.

Asunto(s)

Dieta Alta en Grasa/efectos adversos , Disbiosis/etiología , Endotoxemia/etiología , Enteritis/etiología , Medicina Basada en la Evidencia , Intestinos/inmunología , Obesidad/etiología , Animales , Disbiosis/dietoterapia , Disbiosis/microbiología , Disbiosis/fisiopatología , Endotoxemia/inmunología , Endotoxemia/microbiología , Endotoxemia/prevención & control , Enteritis/inmunología , Enteritis/microbiología , Enteritis/prevención & control , Microbioma Gastrointestinal , Humanos , Intestinos/microbiología , Intestinos/fisiopatología , Obesidad/inmunología , Obesidad/microbiología , Obesidad/fisiopatología , Permeabilidad , Probióticos/uso terapéutico , Simbióticos/administración & dosificación , Aumento de Peso

RESUMEN

Intestinal dysbiosis and metabolic endotoxemia have been associated with metabolic disorders, such as obesity, insulin resistance, and type 2 diabetes (T2D). The main goal of the present study was to evaluate the intestinal dysbiosis in Brazilian T2D patients and correlate these data with inflammatory cytokines and lipopolysaccharides (LPS) plasma concentrations. This study was approved by the Ethics Committees from Barretos Cancer Hospital and all individuals signed the informed consent form. Stool samples were required for DNA extraction, and the V3/V4 regions of bacterial 16S were sequenced using an Illumina platform. Peripheral blood was used to quantify inflammatory cytokines and plasma LPS concentrations, by CBA flex and ELISA, respectively. Statistical analyses were performed using Mann-Whitney and Spearman's tests. Analysis of variance, diversity indexes, and analysis of alpha- and beta-diversity were conducted using an annotated Operational Taxonomic Unit table. This study included 20 patients and 22 controls. We observed significant differences (P < 0.01) in the microbiota composition (beta-diversity) between patients and controls, suggesting intestinal dysbiosis in Brazilian T2D patients. The prevalent species found in patients' feces were the Gram-negatives Prevotella copri, Bacteroides vulgatus, Bacteroides rodentium, and Bacteroides xylanisolvens. The proinflammatory interleukin-6 (IL-6) was significantly increased (P < 0.05) in patients' plasma and LPS levels were decreased. We find correlations between the proinflammatory interferon-gamma with Gram-negatives Bacteroides and Prevotella species, and a positive correlation between the LPS levels and P. copri reads. The P. copri and B. vulgatus species were associated with insulin resistance in previous studies. In this study, we suggested that the prevalence of Gram-negative species in the gut and the increased plasma IL-6 in patients could be linked to low-grade inflammation and insulin resistance. In conclusion, the P. copri and B. vulgatus species could represent an intestinal microbiota signature, associated with T2D development. Furthermore, the identification of these Gram-negative bacteria, and the detection of inflammatory markers, such as increased IL-6, could be used as diabetes predictive markers in overweight, obese and in genetically predisposed individuals to develop T2D.