Gut microbiome of a porcine model of metabolic syndrome and HF-pEF.

Metabolic syndrome (MetS) is a composite of cardiometabolic risk factors, including obesity, dyslipidemia, hypertension, and insulin resistance, with a range of secondary sequelae such as nonalcoholic fatty liver disease and diastolic heart failure. This syndrome has been identified as one of the greatest global health challenges of the 21st century. Herein, we examine whether a porcine model of diet- and mineralocorticoid-induced MetS closely mimics the cardiovascular, metabolic, gut microbiota, and functional metataxonomic phenotype observed in human studies. Landrace pigs with deoxycorticosterone acetate-induced hypertension fed a diet high in fat, salt, and sugar over 12 wk were assessed for hyperlipidemia, hyperinsulinemia, and immunohistologic, echocardiographic, and hemodynamic parameters, as well as assessed for microbiome phenotype and function through 16S rRNA metataxonomic and metabolomic analysis, respectively. All MetS animals developed obesity, hyperlipidemia, insulin resistance, hypertension, fatty liver, structural cardiovascular changes including left ventricular hypertrophy and left atrial enlargement, and increased circulating saturated fatty acid levels, all in keeping with the human phenotype. A reduction in α-diversity and specific microbiota changes at phylum, family, and genus levels were also observed in this model. Specifically, this porcine model of MetS displayed increased abundances of proinflammatory bacteria coupled with increased circulating tumor necrosis factor-α and increased secondary bile acid-producing bacteria, which substantially impacted fibroblast growth factor-19 expression. Finally, a significant decrease in enteroprotective bacteria and a reduction in short-chain fatty acid-producing bacteria were also noted. Together, these data suggest that diet and mineralocorticoid-mediated development of biochemical and cardiovascular stigmata of metabolic syndrome in pigs leads to temporal gut microbiome changes that mimic key gut microbial population signatures in human cardiometabolic disease.NEW & NOTEWORTHY This study extends a prior porcine model of cardiometabolic syndrome to include systemic inflammation, fatty liver, and insulin sensitivity. Gut microbiome changes during evolution of porcine cardiometabolic disease recapitulate those in human subjects with alterations in gut taxa associated with proinflammatory bacteria, bile acid, and fatty acid pathways. This clinical scale model may facilitate design of future interventional trials to test causal relationships between gut dysbiosis and cardiometabolic syndrome at a systemic and organ level.

Adolescent dietary manipulations differentially affect gut microbiota composition and amygdala neuroimmune gene expression in male mice in adulthood.

Adolescence is a critical developmental period that is characterised by growth spurts and specific neurobiological, neuroimmune and behavioural changes. In tandem the gut microbiota, which is a key player in the regulation of health and disease, is shaped during this time period. Diet is one of the most important regulators of microbiota composition. Thus, we hypothesised that dietary disturbances of the microbiota during this critical time window result in long-lasting changes in immunity, brain and behaviour. C57BL/6 male mice were exposed to either high fat diet or cafeteria diet during the adolescent period from postnatal day 28 to 49 and were tested for anxiety-related and social behaviour in adulthood. Our results show long-lasting effects of dietary interventions during the adolescent period on microbiota composition and the expression of genes related to neuroinflammation or neurotransmission. Interestingly, changes in myelination-related gene expression in the prefrontal cortex following high fat diet exposure were also observed. However, these effects did not translate into overt behavioural changes in adulthood. Taken together, these data highlight the importance of diet-microbiota interactions during the adolescent period in shaping specific outputs of the microbiota-gut-brain axis in later life.

Exploring the Gut Microbiota and Cardiovascular Disease.

Cardiovascular disease (CVD) has been classified as one of the leading causes of morbidity and mortality worldwide. CVD risk factors include smoking, hypertension, dyslipidaemia, obesity, inflammation and diabetes. The gut microbiota can influence human health through multiple interactions and community changes are associated with the development and progression of numerous disease states, including CVD. The gut microbiota are involved in the production of several metabolites, such as short-chain fatty acids (SCFAs), bile acids and trimethylamine-N-oxide (TMAO). These products of microbial metabolism are important modulatory factors and have been associated with an increased risk of CVD. Due to its association with CVD development, the gut microbiota has emerged as a target for therapeutic approaches. In this review, we summarise the current knowledge on the role of the gut microbiome in CVD development, and associated microbial communities, functions, and metabolic profiles. We also discuss CVD therapeutic interventions that target the gut microbiota such as probiotics and faecal microbiota transplantation.

Long-term dietary intake from infancy to late adolescence is associated with gut microbiota composition in young adulthood.

BACKGROUND: Gut microbiota composition as influenced by long-term diet may be associated with the risk of adult chronic diseases. Thus, establishing the relation of long-term diet, particularly starting from early life, with adult microbiota composition would be an important research advance. OBJECTIVE: We aimed to investigate the association of long-term intake of energy, carbohydrate, fiber, protein, and fat from infancy to late adolescence with microbiota composition in adulthood. METHODS: Within the prospective DOrtmund Nutritional and Anthropometric Longitudinally Designed (DONALD) Study, we sampled stool 1 or 2 times within 1 y from 128 adults (median age: 29 y). Microbiota composition was profiled by 16S ribosomal RNA sequencing. Annual dietary records from age 1 to 18 y were retrieved. We estimated trajectories of energy, energy-adjusted carbohydrate, fiber, protein, and fat intake with multilevel models, producing predicted intake at age 1 y and rates of change in intake. A multivariate, zero-inflated, logistic-normal model was used to model the association between intake trajectories and the composition of 158 genera in single-sampled individuals. Associations found in this model were confirmed in double-sampled individuals using a zero-inflated Beta regression model. RESULTS: Adjusting for covariates and temporal differences in microbiota composition, long-term carbohydrate intake was associated with 3 genera. Specifically, carbohydrate intake at age 1 y was negatively associated with Phascolarctobacterium [coefficient = -4.31; false discovery rate (FDR)-adjusted P = 0.006] and positively associated with Dialister (coefficient = 3.06; FDR-adjusted P = 0.003), and the rate of change in carbohydrate intake was positively associated with Desulfovibrio (coefficient = 13.16; FDR-adjusted P = 0.00039). Energy and other macronutrients were not associated with any genus. CONCLUSIONS: This work links long-term carbohydrate intake to microbiota composition. Considering the associations of high carbohydrate intake and microbiota composition with some diseases, these findings could inform the development of gut microbiota-targeted dietary recommendations for disease prevention.