Bacillus subtilis and Bacillus megaterium alleviate colitis induced by DSS and depression-like behavior through the modulation of intestinal flora

Inflammatory bowel disease (IBD) induces chronic intestinal inflammation and, in severe cases, may promote the development of colon cancer. IBD is frequently accompanied by psychiatric comorbidities such as anxiety and depression. Probiotics are known to support intestinal homeostasis through modulation of the gut microbiota and have also been shown to mitigate depression-like behaviors. However, the protective mechanisms of Bacillus species against intestinal inflammation and depression remain unclear. In this study, we investigated the effects of Bacillus subtilis and Bacillus megaterium in a mouse model of DSS-induced colitis and depression-like behavior. Treatment with these Bacillus strains attenuated colitis and neuroinflammation in mice, likely via the TLR-4/NF-κB pathway, and enhanced the expression of brain-derived neurotrophic factor (BDNF). Additionally, administration elevated the abundance of beneficial gut bacteria, including Turicibacter , Prevotellaceae_UCG_001 , and Lactobacillus . Transcriptomic analysis further revealed enrichment of pathways related to immune response, inflammatory regulation, and neural development. These findings suggest that Bacillus subtilis and Bacillus megaterium alleviate colitis and associated depression-like behavior by modulating the gut microbiota and related immune signaling pathways.