Sex-specific effects of voluntary wheel running on behavior and the gut microbiota-immune-brain axis in mice

Abstract

Physical exercise has been positioned as a promising strategy to prevent and/or alleviate anxiety and depression, but the mechanisms underlying its effects on mental health have yet to be entirely determined. Although the prevalence of depression and anxiety in women is about twice that of men, very few studies have examined whether physical exercise could affect mental health differently according to sex. This study examined, in mice, the sex-specific effects of voluntary exercise on body weight, depressive- and anxiety-like behaviors, as well as different markers along the gut microbiota-immune-brain axis. Male and female C57BL/6N mice had voluntary access to running wheels in their home-cages for 24 days or were left undisturbed in identical home-cages without running wheels. Behaviors were then examined in the open field, Splash, elevated plus maze, and tail suspension tests. Gene expression of pro-inflammatory cytokines, microglia activation-related genes, and tight junction proteins was determined in the jejunum and the hippocampus, while microbiota composition and predicted function were verified in cecum contents. Voluntary exercise limited weight gains, reduced anxiety-like behaviors, and altered grooming patterns in males exclusively. Although the exercise intervention resulted in changes to brain inflammatory activity and to cecal microbiota composition and inferred function in both sexes, reductions in the jejunal expression of pro-inflammatory markers were observed in females only. These findings support the view that voluntary exercise, even when performed during a short period, is beneficial for mental and intestinal health and that its sex-specific effects on behavior could be, at least in part, mediated by the gut microbiota-immune-brain axis.

Acetate and succinate benefit host muscle energetics as exercise‐associated post‐biotics

“…The microbial strain that was highly responsive to PoWeR training, Muribaculaceae bacterium DMS 103720, is a member of the family Bacteroidales (originally noted as S24-7), which have the capacity to produce succinate, acetate, and propionate through fermentation of carbohydrates (Lagkouvardos et al, 2019;Ormerod et al, 2016). Previous studies have also found that voluntary wheel running results in a significant increase in Muribaculaceae (Lamoureux et al, 2017;Williams et al, 2023). In these studies, as well as the present study, mice ran on average 7-13 km/day.…”

The inflammatory immunity and gut microbiota are associated with fear response differences in laying hens

“…Extensive research suggests that changes in the gut microbiota are associated with emotional states, as seen in depression, anxiety, and fearfulness disorders, where the gut microbiota composition differs from that of healthy individuals ( Dinan and Cryan, 2013 ). Voluntary wheel running exercise was shown to alleviate depressive and anxious behaviors in mice by positively affecting the gut microbiota and reducing levels of intestinal pro-inflammatory cytokines ( Williams, et al, 2023 ). Changes in the gut microbiota structure are thought to influence intestinal immune responses ( Zhou et al, 2020 ).…”