Multifaceted protection from obesogenic diet-induced dysfunction by whole-food cooked bean

Abstract

Background. Underconsumption of dietary fiber and the milieu of chemicals with which it is associated is a health concern linked to the increasing global burden of chronic diseases such as clinical obesity and metabolic dysfunction-associated steatotic liver disease (MASLD) caused by disrupted metabolic homeostasis due to dietary challenges. Weight control by improving diet quality is a component of the standard of care in the prevention and control of these metabolic diseases. The benefits of fiber are partially attributed to modulation of the gut microbiota, whose composition and function depend on the amount and quality of microbiota-accessible substrates in the diet. Inclusion of pulses, such as common bean (Phaseolus vulgaris L.), is an affordable yet neglected approach to improving diet quality and metabolic outcomes. Whole-food cooked bean is a food type rich in fiber as well as other prebiotics, posing a great potential to positively impact diet-microbiota-host interactions. Regular consumption of common bean, thus, reduces the risk of metabolic impairment. However, its effective dose, the impact of biological sex, and the underlying mechanisms of action are unknown. Methodology. We fed female and male C57BL6/J mice with obesogenic yet isocaloric diets containing 0%, 17.5%, 35%, and 70% of total dietary protein derived from cooked whole-food bean. The microbial communities in the ceca of female and male mice were evaluated via 16S rRNA gene sequencing. Liver tissue was collected for histopathology, lipid quantification, and RNA-seq analyses. Based on the obtained results and using biospecimens from several similarly designed studies, cecal content, feces, liver tissue, and plasma samples were subjected to total bile acid analysis and untargeted metabolomics to further complement the findings. Results. As the bean dose increased, the Bacillota:Bacteroidota ratio (formerly referred to as the Firmicutes:Bacteroidetes ratio) was reduced and α-diversity decreased, whereas the community composition was distinctly different between the diet groups according to β diversity. These effects were more pronounced in female mice compared to male mice. Compositional analyses identified a dose-responsive bean-induced shift in microbial composition. With an increasing bean dose, Rikenellaceae, Bacteroides, and RF39, which are associated with health benefits, were enhanced. More taxa, however, were suppressed, among which were Allobaculum, Oscillospira, Dorea, and Ruminococcus, which are predominantly associated with chronic disease risk. Moreover, Beans qualitatively and quantitatively diminished hepatic fat deposition at the 35% dose in female mice and 70% dose in male mice. Bean-induced differentially expressed genes (DEGs) most significantly mapped to hepatic steatosis and revealed dose-responsive inhibition of de novo lipogenesis markers (Acly, Acaca, Fasn, Elovl6, Scd1) and triacylglycerol biosynthesis, activation of triacylglycerol degradation, and downregulation of sterol regulatory element-binding transcription factor 1 (SREBF1) signaling. Upregulated fatty acid β-oxidation was more prominent in females, while suppression of Cd36-mediated fatty acid uptake—in males. Sex-dependent bean effects also involved DEGs patterns downstream of peroxisome proliferator-activated receptor α (PPARα) and MLX-interacting protein-like (MLXIPL). Finally, bean-fed mice had increased cecal bile acid content and excreted more bile acids per gram of feces. Consistent with these effects, increased synthesis of bile acids in the liver was observed. Microbial composition and capacity to metabolize bile acids were markedly altered by bean, with greater prominence of secondary bile acid metabolites in bean-fed mice, i.e., microbial metabolites of chenodeoxycholate/lithocholate increased while metabolites of hyocholate were reduced. Conclusions. Investigation of the origins of the dose-dependent and biological sex differences in response to common bean consumption may provide insights into bean-gut microbiota-host interactions important to developing food-based precision approaches to chronic disease prevention and control. In rendering mice resistant to obesogenic diet-induced MASLD and obesity, lipid metabolism emerges as one of the main targets of bean effects, especially in the liver. Inhibited uptake of free fatty acids and de novo biosynthesis thereof appear to be central molecular responses to bean consumption in the liver, rendering suppressed accumulation of lipid therein. Furthermore, bean consumption sequesters bile acids, increasing their hepatic synthesis and enhancing their diversity through microbial metabolism. Bean-induced changes in bile acid metabolism have the potential to improve dyslipidemia.