Physical activity shapes the intestinal microbiome and immunity of healthy mice but has no protective effects against colitis in MUC2^-/- mice

Abstract

The interactions among humans, their environment, and the trillions of microbes residing within the human intestinal tract form a tripartite relationship that is fundamental to the overall health of the host. Disruptions in the delicate balance between the intestinal microbiota and their host immunity are implicated in various chronic diseases including inflammatory bowel disease (IBD). There is no known cure for IBD, therefore, novel therapeutics targeting prevention and symptoms management are of great interest. Recently, physical activity in healthy mice was shown to be protective against chemically-induced colitis, however the benefits of physical activity during or following disease onset is not known. In this study, we examine whether voluntary wheel running is protective against primary disease symptoms in a mucin 2 deficient (Muc2-/-) life-long model of murine colitis. We show that 6 weeks of wheel running in healthy C57BL/6 mice leads to distinct changes in fecal bacteriome, increased butyrate production, and modulation in colonic gene expression of various cytokines, suggesting an overall primed anti-inflammatory state. However, these physical activity-derived benefits are not present in Muc2-/- mice harboring a dysfunctional mucosal layer from birth, ultimately showing no improvements in clinical signs. We extrapolate from our findings that while physical activity in healthy individuals may be an important preventative measure against IBD, for those with a compromised intestinal mucosa, a commonality in IBD patients, these benefits are lost.

Lactate in contemporary biology: a phoenix risen

“…The concentration of lactate in human faeces is relatively low (< 5 mm) because of the presence of bacteria that convert lactate to butyrate (Duncan et al 2004). More recently, we have learned that physical exercise and physical fitness encourage diversity of species including those that act to convert lactate to butyrate (Estaki et al 2016(Estaki et al , 2020. Recently also, the presence of 'performance-enhancing' gut microbes, members of the genus Veillonella, in the stools of marathon runners (Scheiman et al 2019) have been found.…”

“…More recently, we have learned that physical exercise and physical fitness encourage diversity of species including those that act to convert lactate to butyrate (Estaki et al . 2016, 2020). Recently also, the presence of ‘performance‐enhancing’ gut microbes, members of the genus Veillonella , in the stools of marathon runners (Scheiman et al .…”