TNF-α antagonist etanercept reverses age-related increases in constipation in mice

In an exciting new paper led by STRAND Researchers Dr Bhavik Patel, Dr Mel Flint and Dr Mark Yeoman, alongside colleagues from The Open University examining a potential novel treatment class for chronic constipation has been published in the prestigious  Nature Scientific Reports. The paper examines the use of 5-HT, an important pro-kinetic agent in the colon, to see if alterations in colonic 5-HT signalling underlie age–related changes in faecal output in mice and whether these changes were due to an increase in TNF-α. The researchers observed reduced faecal output and water content in aged animals, as well as increased mucosal 5-HT availability and TNF-α expression and decreased mucosal SERT expression and 5-HIAA. The treatment of old mice with Etanercept reversed these changes, suggesting that age-related changes in TNFα expression are an important regulator of mucosal 5-HT signalling and pellet output and water content in old mice. This study points to “anti-TNFα” drugs as potential treatments for age-related chronic constipation.

Patel, BA, Fidalgo, S, Wang, C, Parmar, L, Mandona, K, Panossian, A, Flint, MS, Ranson, RN, Saffrey, MJ  & Yeoman, MS (2017) The TNF-α antagonist etanercept reverses age-related decreases in colonic SERT expression and faecal output in mice. Sci. Rep. 7, 42754; doi: 10.1038/srep42754

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