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bioRxiv · 10.1101/2025.04.16.649253

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

Goutam Singh, M.·Bora, H. K.·Wahengbam, R.
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Abstract

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-1{beta}, 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. Highlights of findingsO_LIMetagenomics reveals changes in gut microbiota composition associated with diet-induced atherogenesis and consumption of traditional fermented soybean, hawaijar, in C57BL/6 mice. C_LIO_LIFermented soybean supplementation in atherogenic diet reduces atherogenic lesions, expression of genes associated with inflammatory response (IL-1{beta}, ICAM-1, CD4, and FoxP3), and serum LPS endotoxin level. C_LIO_LIFermented soybean consumption improves gut barrier integrity, indicated by decreased gut permeability and elevated expressions of tight junction genes (Ocln, Cldn-1, Cldn-4). C_LIO_LIDietary fermented soybean supplementation promotes eubiosis of atherogenic diet-induced dysbiotic microbiota with a profile characteristic of a normal diet. C_LIO_LIFive core microbiota members, including Ligilactobacillus spp., CAG-485 sp002493045 and others, are lost under atherogenic diet regime; however, only Muribaculum gordoncarteri and Duncaniella dubosii are restored with fermented soybean supplementation. C_LIO_LIEubiosis of diet-induced dysbiotic microbiota upon fermented soybean supplementation is associated with a predicted reduction in major metabolic pathways and a distinct increase in terpenoids and polyketide metabolism. C_LI Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=197 SRC="FIGDIR/small/649253v1_ufig1.gif" ALT="Figure 1"> View larger version (79K): org.highwire.dtl.DTLVardef@77bf59org.highwire.dtl.DTLVardef@1b38d1forg.highwire.dtl.DTLVardef@f62a97org.highwire.dtl.DTLVardef@1665035_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Goutam Singh, M., Bora, H. K., Wahengbam, R.. 2025-04-17. Shift in gut microbiota composition and mitigation of diet-induced atherogenesis in mice after prolonged consumption of a traditionally fermented soybean. https://doi.org/10.1101/2025.04.16.649253

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