Glucocorticoids coordinate changes in gut microbiome composition in wild North American red squirrels

Abstract

The gut microbiome impacts host health and fitness, in part through the diversification of gut metabolic function and pathogen protection. Elevations in glucocorticoids (GCs) appear to reduce gut microbiome diversity in experimental studies, suggesting that a loss of microbial diversity may be a negative consequence of increased GCs. However, given that ecological factors like food availability and population density may independently influence both GCs and microbial diversity, understanding how these factors structure the GC-microbiome relationship is crucial to interpreting its significance in wild populations. Here, we used an ecological framework to investigate the relationship between GCs and gut microbiome diversity in wild North American red squirrels (Tamiasciurus hudsonicus). As expected, higher GCs predicted lower gut microbiome diversity and an increase in metabolic taxa. Surprisingly, but in line with prior empirical studies on wild animals, gastrointestinal pathogens decreased as GCs increased. Both dietary heterogeneity and an upcoming food pulse exhibited direct effects on gut microbiome diversity, whereas conspecific density and reproductive activity impacted diversity indirectly via changes in host GCs. Our results provide evidence of a gut–brain axis in wild red squirrels and highlight the importance of situating the GC-gut microbiome relationship within an ecological framework.

Gut Bacterial Communities Vary across Habitats and Their Diversity Increases with Increasing Glucocorticoids in Toad Tadpoles

“…In fish, the gut microbiome affects the "gut-brain axis" such that when the main fish glucocorticoid stress hormone, cortisol, is elevated, gut microbiome diversity is reduced [10]. Similar results have been found for other species (red squirrel [32], fish [37]) whereas other studies have found no relationship in unmanipulated populations [38][39][40]. Anthropogenic environments can alter glucocorticoid physiology in wildlife including aquatic vertebrates [41,42], but little is known about the relationship between land use change, associated shifts in host and environmental microbial communities, and stress physiology in the host.…”

“…The bi-directional gut-brain axis likely works together adaptively and helps cope with environmental change [32,33]. We found a positive correlation between baseline corticosterone release rate and two measures of diversity in host gut bacterial communities (ASV richness and Shannon diversity).…”

“…Glucocorticoids are metabolic hormones that aid in energy regulation [31]. Elevated glucocorticoids are associated with altered host microbial biodiversity (reviewed in [32]). In turn, host gut microbiome can also modulate stress response of the HPA/HPI axis and this bi-directional interaction is known as the 'gut-brain axis' [33][34][35].…”

Characterization and diagnostic value of the gut microbial composition in patients with minimal change disease

“…Previous studies have shown that drugs, such as corticosteroids, tacrolimus, or metformin, can have varying degrees of impact on the host’s gut microbiota ( Jiang et al, 2018 ; Pastor-Villaescusa et al, 2021 ; Petrullo et al, 2022 ). However, in our project, drug application did not seem to affect the effectiveness of the diagnostic model.…”

Aging gut microbiota of wild macaques are equally diverse, less stable, but progressively personalized

“…Alternatively, the general decline in activity above and beyond social activity may have driven the increase in microbiota personalization with age if aging individuals each sample a smaller and different portions of the environment when they rest more, feed less, and roam less. Furthermore, the physiological regulation of overall activity levels via hormones may affect the gut microbiota [ 74 , 75 ] in more profound ways than a decline in social transmission of microbiota.…”