ARS | Publication request: B-vitamin deficiency is protective against DSS-induced colitis in mice

Submitted to: American Journal of Physiology - Gastrointestinal and Liver Physiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: May 15, 2011
Publication Date: N/A

Interpretive Summary: Inflammatory bowel disease (IBD) is a disease of the intestine that often begins in adolescents and represents a substantial health care problem in the U.S. The impact of intestinal metabolism on the severity of IBD is poorly understood. Our previous studies showed that substantial metabolism of the dietary amino acid, methionine, and production of homocysteine occurs in the intestine. Homocysteine is an amino acid that has been linked to IBD patients and these patients can also experience B-vitamin deficiency. B-vitamins, especially B6, are important for proper methionine metabolism. Thus, the aim of the current study was to test whether altering the metabolism of methionine and production of homocysteine by feeding a vitamin B6 deficient diet would alter the severity of colitis in growing mice. Colitis, or inflammation of the colon, was induced in mice by adding a chemical irritant to the drinking water, called dextran sodium sulfate. Our results showed that mice fed a B6 deficient diet experienced less colitis and less injury to the colon. This was unexpected since mice fed the B6 deficient diet had increased blood homocysteine. Our results suggest that vitamin B6 deficiency and elevated Hcys did not cause more severe colitis in mice. Further studies are needed to test the role of vitamin B6 status and dietary B6 supplements in IBD patients.

Technical Abstract: Vitamin deficiencies are common in patients with inflammatory bowel disease (IBD). Homocysteine (Hcys) is a thrombogenic amino acid produced from methionine (Met) and its increase in IBD patients indicates a disruption of Met metabolism, yet the role of Hcys and Met metabolism in IBD is not well understood. We hypothesized that disrupted Met metabolism from a B-vitamin deficient diet would exacerbate experimental colitis. Mice were fed a B[6]-B[12] deficient or control diet for two weeks and then treated with DSS to induce colitis. We monitored disease activity during DSS treatment and collected plasma and tissue for analysis of inflammatory tissue injury and Met metabolites. We also quantified Met cycle activity by measurements of "in vivo" Met kinetics using [1-(13)C-methyl-(2)H[3]] methionine infusion in similarly treated mice. Unexpectedly, we found mice given the B-vitamin deficient diet had improved clinical outcomes, including increased survival, weight maintenance, and reduced disease scores. We also found lower histological disease activity and proinflammatory gene expression (TNF alpha and iNOS) in the colon in deficient diet mice. Metabolomic analysis showed evidence that these effects were associated with deficient B[6], as markers of B[12] function were only mildly altered. "In vivo" methionine kinetics corroborated these results, showing that the deficient diet suppressed transsulfuration, but increased remethylation. Our findings suggest that disrupted Met metabolism due to B[6] deficiency reduces the inflammatory response and disease activity in DSS challenged mice. These results warrant further human clinical studies to determine whether B[6] deficiency and elevated Hcys in IBD patients contributes to disease pathobiology.