RESUMEN
High-fat diets are used to induce adverse alterations in the intestinal microbiota, or dysbiosis, generalized inflammation and metabolic stress, which ultimately may lead to obesity. The influence of dietary whey proteins, whether intact or hydrolyzed, has been reported to improve glucose homeostasis and reduce stress. Therefore, the purpose of this work was to test if dietary milk-whey proteins, both in the intact form and hydrolyzed, could have an effect on the compositional changes of the cecal microbiota that can be induced in mice when receiving a high-fat diet in combination with the standard casein. Male C57BL/6 mice were fed a control casein diet (AIN 93-G); high-fat-casein (HFCAS); high-fat-whey protein concentrate (HFWPC) and high-fat whey-protein hydrolysate (HFWPH) for 9weeks. The intestinal microbiota composition was analyzed by 16S-rRNA of the invariant (V1-V3) gene, potentially endotoxemic lipopolysaccharide (LPS) release was determined colorimetrically, and liver fat infiltration assessed by light microscopy. The high-fat diet proved to induce dysbiosis in the animals by inverting the dominance of the phylum Firmicutes over Bacteroidetes, promoted the increase of LPS and resulted in liver fat infiltration. The whey proteins, whether intact or hydrolyzed, resisted the installation of dysbiosis, prevented the surge of circulating LPS and prevented fat infiltration in the liver. It is concluded that dietary whey proteins exert metabolic actions that tend to preserve the normal microbiota profile, while mitigating liver fat deposition in mice consuming a high-fat diet for nine weeks. Such beneficial effects were not seen when casein was the dietary protein. The hydrolyzed whey protein still differed from the normal whey protein by selectively protecting the Bacteroidetes phylum.
RESUMEN
BACKGROUND: The toll-like receptor 4 (TLR4) and inducible nitric oxide synthase are proteins from the innate immune system that, when activated, can induce insulin resistance. Polymorphisms in these genes, TLR4 and NOS2, respectively, could affect the immune response, as well as the prevalence of Type 2 diabetes (T2DM). OBJECTIVE: The aim of the present study was to investigate the contribution of four polymorphisms (two from TLR4 and two from NOS2) to susceptibility to T2DM in a southeast Brazilian population. DESIGN: A total of 211 patients with T2DM and 200 unrelated controls were genotyped for the Asp299Gly and Thr399Ile polymorphisms of the TLR4 gene and for the insertion (I)/deletion (D) AAAT and (CCTTT)n polymorphisms of the NOS2 promoter gene. RESULTS: With regard to the NOS2 promoter region, the data showed that the I allele of the I/D AAAT polymorphism was more prevalent in the T2DM group and that the L/L genotype of the (CCTTT)n polymorphism was also more frequent in the same group. In contrast, the 299Gly allele and the 399Ile allele from the Asp299Gly and Thr399Ile TLR4 gene polymorphisms, respectively, were associated with protection of T2DM. It is believed that the persistence of these genetic variations in human populations may be indicative of a selective advantage in the face of different environmental pressures. CONCLUSIONS: Genetic variations in the NOS2 gene promoter and TLR4 coding sequence may lead to deleterious and protective effects, respectively, arising from altered function of the innate immune system in patients with T2DM.
Asunto(s)
Diabetes Mellitus Tipo 2/genética , Óxido Nítrico Sintasa de Tipo II/genética , Receptor Toll-Like 4/genética , Glucemia/genética , Brasil/epidemiología , Diabetes Mellitus Tipo 2/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mutagénesis Insercional , Polimorfismo Genético , Prevalencia , Regiones Promotoras Genéticas , Eliminación de SecuenciaRESUMEN
Most reports of autoimmune response during infection with the parasite Trypanosoma cruzi have dealt with the cardiomyopathic form of Chagas' disease, but little is known about the mechanisms of tissue damage involved in the gastrointestinal form, which was studied here. Chronically infected patients with a severe gastrointestinal form of Chagas' disease present increased antibody production and proliferative responses to peripheral myelin components, such as myelin basic protein (MBP), which is homologous to the P1 protein fraction of peripheral myelin. T lymphocytes preferentially recognize a region on the MBP molecule (1-30), which suggests that the MBP is a potential target on the peripheral nerve for autoimmune reactions in patients with gastrointestinal lesions resulting from Chagas' disease.