Butyrate Treatment of DSS-Induced Ulcerative Colitis Affects the Hepatic Drug Metabolism in Mice

The development of inflammatory bowel disease (IBD) is associated with alterations in the gut microbiota. There is currently no universal treatment for this disease, thus emphasizing the importance of developing innovative therapeutic approaches. Gut microbiome-derived metabolite butyrate with its well-known anti-inflammatory effect in the gut is a promising candidate. Due to increased intestinal permeability during IBD, butyrate may also reach the liver and influence liver physiology, including hepatic drug metabolism. To get an insight into this reason, the aim of this study was set to clarify not only the protective effects of the sodium butyrate (SB) administration on colonic inflammation but also the effects of SB on hepatic drug metabolism in experimental colitis induced by dextran sodium sulfate (DSS) in mice. It has been shown here that the butyrate pre-treatment can alleviate gut inflammation and reduce the leakiness of colonic epithelium by restoration of the assembly of tight-junction protein Zonula occludens-1 (ZO-1) in mice with DSS-induced colitis. In this article, butyrate along with inflammation has also been shown to affect the expression and enzyme activity of selected cytochromes P450 (CYPs) in the liver of mice. In this respect, CYP3A enzymes may be very sensitive to gut microbiome-targeted interventions, as significant changes in CYP3A expression and activity in response to DSS-induced colitis and/or butyrate treatment have also been observed. With regard to medications used in IBD and microbiota-targeted therapeutic approaches, it is important to deepen our knowledge of the effect of gut inflammation, and therapeutic interventions were followed concerning the ability of the organism to metabolize drugs. This gut-liver axis, mediated through inflammation as well as microbiome-derived metabolites, may affect the response to IBD therapy.

Automated summary

The development of inflammatory bowel disease (IBD) is closely related to changes in the gut microbiota. Butyrate, a gut microbiome-derived metabolite with anti-inflammatory effects, shows promise as a potential treatment option for IBD. This study aimed to investigate the protective effects of sodium butyrate (SB) administration on colonic inflammation and its effects on hepatic drug metabolism. The results revealed that butyrate pre-treatment can alleviate gut inflammation and improve the integrity of the colonic epithelium in mice with induced colitis. Additionally, butyrate was found to affect the expression and enzyme activity of certain cytochromes P450 (CYPs) in the liver. These findings highlight the importance of understanding the impact of gut inflammation and therapeutic interventions on drug metabolism in the context of IBD therapy.