Protective Potential of <i>Limosilactobacillus fermentum</i> Strains and Their Mixture on Inflammatory Bowel Disease via Regulating Gut Microbiota in Mice

The aim of this study is to investigate the protective potential of <i>Limosilactobacillus fermentum</i> IM57, IR51, and IR62 strains, isolated from infant feces, and their mixture against inflammatory bowel disease (IBD). The strains exhibited robust antioxidant activities and anti-inflammatory properties in RAW 264.7 cells. Subsequently, the potential protective effects of each of these three strains, along with their mixture, were evaluated in a murine colitis model induced by dextran sodium sulfate (DSS). Noteworthy improvements in physiological parameters such as body weight, disease activity index, and colon length were observed in mice treated with the mixture followed by IR62. Additionally, administration of each strain and the mixture mitigated DSS-induced changes in gut microbiota composition with increased abundance of <i>Lactobacillus</i>, <i>Bifidobacterium</i>, <i>Ruminococcus</i>, and <i>Muribaculum</i>, compared to DSS-treated mice. Interestingly, the abundance of <i>Muribaculum</i> increased approximately 2.4-fold after administration of the mixture compared to before administration. Additionally, the concentration of short-chain fatty acids (SCFAs) was significantly reduced in DSS-treated group compared to the control group, while the mixture treatment group had the highest concentration of SCFAs. Furthermore, due to these changes in microbiota and the leading metabolites induced by treatment of the mixture, DSS-induced dysregulation of inflammationand barrier function-related mRNA expressions was significantly inhibited in the group fed with the mixture. Consequently, this study indicates that the multi-strain mixture of <i>L. fermentum</i> strains may play a crucial role in modulating gut microbiota, thereby alleviating IBD through the synergistic effect of the individual effects of the three strains.