Inflammatory bowel diseases (IBDs) are debilitating conditions with no known cure. Recent evidence suggests that elevated intestinal hydrogen sulfide (H 2 S) synthesis promotes healing and reduces inflammation. H 2 S is synthesized from cysteine largely via vitamin B 6 -dependent enzymes. People with IBD are also at increased risk of hyperhomocysteinemia, a condition that is often caused by vitamin B deficiency. Dietary induction of vitamin B deficiency markedly increased serum homocysteine levels and worsened colitis in rodents. The latter was due to the absence of the typical injury-induced elevation of H 2 S synthesis. Interleukin-10 plays a key role in increasing H 2 S synthesis, attenuating the severity of colitis, and reducing serum homocysteine levels. The H 2 S–interleukin 10 axis may be a viable target for therapy of IBD.