Multi-omics profiling unraveled the health benefits of fermented milk derived Bifidobacterium animalis subsp. lactis via gut-testis axis. Mice

Rapid urbanization, medication, and modern dietary patterns are the main challenges for impaired fertility with lack of effective therapy. Emerging evidence has found that reproductive disorders may closely correlate to intestinal damage or occasionally worsen by the side effects of medication. Hence, development of dietary supplement as the medicine alternative is valuable for intestinal-linked reproductive health. Milk and dairy products are essential in diet nutrition and gut health with great potential functional ingredients. Bifidobacterium animalis subsp. lactis NJ241 (NJ241) is a potential probiotic isolated from natural fermented bovine milk with lack of investigation. This study aims to investigate the molecular mechanisms of NJ241 on colitis and its linked reproductive disorders. Hematological analysis, histopathological examination, and real time transcription-polymerase chain reaction (RT-PCR) analysis were applied for conjoined identification. The biomarker microbes and their correlated metabolites were further explored by 16S rRNA sequencing and metabolomics. Results indicated that NJ241 could effectively restore the expression levels of Claudin-2 and MLCK1 to decrease intestinal permeability. Further analysis found that NJ241 could markedly inhibit the expression level of IL-6 to regulate the inflammatory levels and metabolic homeostasis. Interestingly, integrated gut microbiota sequencing and metabolomics implied that NJ241 may effectively improve colitis-induced reproductive disorders through inhibiting TLR4 signaling by targeting the modulation of Akkermansia muciniphila and its metabolite trans-ferulic acid. Current findings consistently illustrated the potential molecular mechanism of NJ241 in managing colitis for ameliorating reproductive disorders. Additionally, NJ241 could be used as a promising probiotic additive for fortified dairy product industrialization. It also elicits corroborative evidence for the prospective application of natural fermented bovine milk in promoting reproductive health benefits.