Grant: Travel Awards - Institute Community Support

Inflammatory bowel disease (IBD) is a chronic condition that causes persistent inflammation in the gut and increases vulnerability to infections and environmental stress. While it is known that changes in gut bacteria, called gut dysbiosis, play a key role in IBD, the mechanisms by which these microbial imbalances contribute to long-term inflammation remain poorly understood. In this study, using a mouse model of colitis, we discovered a novel link between the gut and the bone marrow, where blood and immune cells are generated. We found that gut dysbiosis disrupts hematopoietic stem cell function, skewing their development toward pro-inflammatory macrophages. These macrophages perpetuate chronic intestinal inflammation and increase susceptibility to additional stress. Importantly, restoring gut microbial balance through fecal microbiota transplantation (FMT) reduced the production of inflammatory macrophages, promoted recovery from intestinal inflammation, and improved resilience to external insults. Our findings reveal a previously unrecognized gut-bone marrow axis in IBD and highlight microbiota-driven programming of HSCs as a potential therapeutic target. Targeting this pathway could break the cycle of chronic inflammation, restore immune balance, and limit disease progression. These results provide new insights into how the gut microbiome influences systemic immunity and open the door to innovative strategies for treating IBD and related inflammatory disorders.