This week: anti-TNFα treatment shows promise in early Crohn’s disease, rifaximin takes on over-sensitive gut nerves and mast cells might be behind stress-induced tummy troubles.
Hit Them Early and Hit Them Hard
Specialists treating newly diagnosed cases of Crohn’s disease (CD) in children usually follow a specific treatment regimen: corticosteroids followed by immunomodulators, like azathioprine. However, scientists funded by the Crohn’s and Colitis Foundation of America wondered if better results could be obtained with another protocol, a protocol including early use of anti-TNFα. In a huge collaborative study using patients that were matched for age and disease severity, CD severity was followed for a year after initial treatments. It was discovered that early treatment with anti-TNFα led to a significantly better clinical and growth outcomes than the typical regimen.
Rifaximin Settles Gut Nerves
Some intestinal disturbances, including irritable bowel syndrome (IBS), can be attributed to what is called “visceral hyperalgesia,” a situation of heightened nerve sensitivity. The antibiotic rifaximin has shown promise for IBS treatment, but little was known about its mechanism. Using two visceral hyperalgesia models in rats based on chronic stress, scientists from the University of Michigan determined that these models were associated with alterations in the microflora, increased intestinal permeability and mucosal inflammation. Rifaximin, unlike a control antibiotic, eliminated these dysfunctions. The benefits appeared to be linked to an increase in beneficial bacteria species in the gut after treatment that was not found after other kinds of antibiotic treatment.
Mast Cells Behind Nervous Gut Permeability
Most of us are familiar with nervous gut trouble, especially when we have to speak in front of a crowd. Belgium scientists suspected that corticotropin-releasing hormone (CRH) could be playing a role in stress-induced gut permeability. After administering CRH to volunteers, they found changes in gut permeability similar to those found after public speaking. One target of CRH is the mast cell, which has all of the right tools to cause a good case of tummy trouble. To find out if the mast cell could be the culprit behind stomach butterflies, they asked volunteers to take the mast cell blocker disodium cromoglycate and either give a presentation or take CRH. Blocking mast cells alleviated intestinal permeability in both situations.
- Thomas D Walters, M. D., MiOk Kim, P. D., Lee A Denson, M. D., Anne M Griffiths, M. D., Marla Dubinsky, M. D., James Markowitz, M. D., et al. (2013). Comparative Effectiveness of Early Therapy with Anti-Tumor Necrosis Factor-α vs an Immunomodulator in Children With Crohn’s Disease. Gastroenterology, 1–30. doi:10.1053/j.gastro.2013.10.027
- Vanuytsel, T., van Wanrooy, S., Vanheel, H., Vanormelingen, C., Verschueren, S., Houben, E., et al. (2013). Psychological stress and corticotropin-releasing hormone increase intestinal permeability in humans by a mast cell-dependent mechanism. Gut. doi:10.1136/gutjnl-2013-305690
- Xu, D., Gao, J., Gillilland, M., Wu, X., Song, Il, Kao, J. Y., & Owyang, C. (2013). Rifaximin Alters Intestinal Bacteria and Prevents Stress-Induced Gut Inflammation and Visceral Hyperalgesia in Rats. Gastroenterology, 1–48. doi:10.1053/j.gastro.2013.10.026