A butyrate-producing synbiotic mitigates intestinal inflammation in a murine colitis model

Abstract

Inflammatory bowel disease (IBD) is a chronic condition characterized by intestinal inflammation and gut dysbiosis, with limited treatment options primarily focused on immune-modulating therapies. Among potential therapeutic agents, butyrate has emerged as a promising candidate due to its anti-inflammatory and gut-restorative properties. However, direct administration of butyrate poses significant challenges, including its rapid absorption, uneven distribution within the intestinal tract, and an unpleasant odor that reduces patient compliance. To address these issues, we evaluated the therapeutic potential of Bacillus subtilis BM107, a strain selected for its superior butyrate-producing capabilities and established bacterial safety. BM107 efficiently hydrolyzed tributyrin (TB), a butyrate prodrug, producing substantial butyrate levels in TB-supplemented media. In a dextran sodium sulfate-induced colitis mouse model, co-administration of BM107 and the TB diet significantly improved inflammatory indices, such as reduced disease activity index scores, increased colon length, and restored body weight. Additionally, this combination treatment markedly improved gut microbiome composition, restoring microbial diversity and balance. Furthermore, butyrate levels in the cecum contents of the TB + BM107 group were restored to levels comparable to those in healthy controls, demonstrating the ability of this approach to promote gut homeostasis and intestinal recovery. These findings highlight the therapeutic potential of BM107 combined with a TB diet as a safe, effective, and innovative strategy for addressing gut dysbiosis and inflammation in IBD, paving the way for the development of microbiome-based bacterial therapeutics to improve patient outcomes.