What’s Missing in Ulcerative Colitis and T Cell Derived Opioids

Met-enkephalin 1plx model 1
Enkephalin. T cells take away the pain with their own opioids.
Two important bacterial species are lost in ulcerative colitis patient microflora, genes behind bacterial colonization are discovered and T cells have a new role as the intestinal drug dealer.

Bacterial Colonization Genes Discovered

In the journal Nature this week, there is an article that describes bacterial genes that are needed for colonization in the colon. These genes, dubbed commensal colonization factors (ccf), are needed for the stabile colonization of bacteria within a host colon, the ability to nestle in mucus, and the control of population size. These genes, found so far in Bacteroides species, are activated by components found in the mucus, and lead the authors to believe that the colon may control populations of bacteria and their long-term stability by providing specific substrates as nutrients. For inflammatory bowel disease (IBD) patients this could lead to new insights about how to control the intestinal microflora and why IBD patient flora is different.

Missing Bacteria in Ulcerative Colitis

Initial studies have indicated that IBD patient intestinal microbiota are different than that of healthy individuals. However, more attention has been paid to Crohn’s disease (CD) than to ulcerative colitis (UC). Now, a Belgian team has addressed that issue in the journal, Gut. They have found that the changes in UC are different than that found in CD. Ulcerative colitis patients have significantly less Roseburia hominis and Faecalibacterium prausnitzii, and their reductions are indirectly correlated with disease activity. These bacteria are known for the production of butyrate, which functions as a nutrient and an immunomodulatory factor in the colon.

T Cells, the Local Opioid Supplier

A French study has found a new role for effector T cells in the gut during colitis: opioid producers. This study, accepted by Gastroenterology, demonstrates that murine T helper 1 and 17 cells produce enkephalin peptides. Enkephalin peptides are endogenous opioid receptor ligands. Using the T cell transfer model of colitis, they determined that T cells causing colitis simultaneously produce opioids. By combining the colitis model with opioid receptor blockers, they determined that these receptors were controlling visceral sensitivity, and therefore, the T cells were likely playing an analgesic function with their enkephalin secretion.

References

  • Boué, J., Basso, L., Cenac, N., Blanpied, C., Rolli-Derkinderen, M., Neunlist, M., et al. (2013). Accepted Manuscript. Gastroenterology, 1–36. doi:10.1053/j.gastro.2013.09.020
  • Lee, S. M., Donaldson, G. P., Mikulski, Z., Boyajian, S., Ley, K., & Mazmanian, S. K. (2013). Bacterial colonization factors control specificity and stability of the gut microbiota. Nature, 501(7467), 426–429. doi:10.1038/nature12447
  • Machiels, K., Joossens, M., Sabino, J., De Preter, V., Arijs, I., Eeckhaut, V., et al. (2013). A decrease of the butyrate-producing species Roseburia hominis and Faecalibacterium prausnitzii defines dysbiosis in patients with ulcerative colitis. Gut. doi:10.1136/gutjnl-2013-304833

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