Shift in gut microbiota composition and mitigation of diet-induced atherogenesis in mice after prolonged consumption of a traditionally fermented soybean

Dietary choices and gut microbiota alterations are linked to the rising prevalence of cardiovascular diseases, including atherosclerosis. Fermented foods, recognized for their health benefits, are known for maintaining cardiovascular health, yet their impact on atherogenesis and associated gut microbiota changes is poorly understood. Here, we showed the restorative potential of long-term dietary supplementation with a traditional Indian fermented soybean, hawaijar , in mitigating atherogenic lesions formation and gut microbiota alteration induced by an atherogenic diet in C57BL/6 mice. The diet caused atherogenesis, characterized by increased inflammatory gene expression (IL-1β, ICAM-1, CD4, FoxP3), elevated serum LPS endotoxin levels, and compromised gut health, indicated by increased permeability and decreased expression of tight junction and mucin-producing genes essential for gut barrier integrity (Ocln, Cldn-1, Cldn-4, Muc-2). Metagenomic analysis revealed diet-induced gut dysbiosis, evidenced by an elevated Firmicutes-to-Bacteroidetes ratio, reduced bacterial diversity, and a shift in bacterial composition, including a loss of beneficial Ligilactobacillus spp. while pathogenic Romboutsia spp., Escherichia spp., and Clostridium spp. emerged. Conversely, feeding hawaijar for sixteen weeks significantly improved atherogenesis, reducing atherosclerotic lesions, serum endotoxins, and inflammatory gene expression. It corrected dysbiosis, restoring gut microbiota to a healthy composition and enhancing gut barrier integrity by reducing permeability and increasing tight junction gene expression. Core beneficial bacteria such as Phocaeicola sartorii , Faecalibaculum rodentium , and Akkermansia muciniphila resurged, alongside the recovery of Muribaculum gordoncarteri and Duncaniella dubosii , which were lost in the atherogenic condition. Gut eubiosis upon fermented soybean supplementation was also linked with a predicted reduction in major metabolic pathways and a distinct increase in terpenoids and polyketide metabolism. The study highlights the importance of traditional fermented soybean in restoring gut microbiota diversity and gut health against dietary-induced dysbiosis, providing insights into its role in modulating atherogenesis in a gut microbiota-dependent manner.