Effects of the anti-inflammatory drug budesonide on the gut microbiota and cytokine production of 13-lined ground squirrels during pre-hibernation fattening

The gut microbiome is essential for maintaining organismal health. Gut microbiota may be disrupted through external factors like dietary change, which can lead to gut inflammation, resulting in obesity. Hibernating mammals develop low-grade gut inflammation when they accumulate fat deposits in preparation for hibernation, making them useful models for studying the relationship between the microbiome, inflammation, and weight gain. Nonsteroidal anti-inflammatory drugs and steroids are commonly used in humans to target gut inflammation, but how these drugs affect the gut microbiome and its stability is unclear. We investigated the effect of the glucocorticoid drug budesonide on the gut microbiome and cytokine levels of an obligate hibernator, the 13-lined ground squirrel, during the fattening season. We used 16S rRNA gene sequencing to characterize bacterial communities in the lumen and mucosa of the cecum and colon and measured proinflammatory [tumor necrosis factor-α (TNF-α)/interleukin 6 (IL-6)] and anti-inflammatory (IL-10) cytokine levels. Budesonide affected the microbiome only in the cecum lumen, where bacterial diversity was higher in the control group, and communities significantly differed between treatments. Across gut sections, <i>Marvinbryantia</i> and <i>Enterococcus</i> were significantly higher in the budesonide group, whereas <i>Sarcina</i> was higher in the control group. TNF-α and IL-6 levels were higher in control squirrels compared with the budesonide group, but there was no difference in IL-10 levels. Overall, budesonide treatment affected the microbial community and diversity of 13-lined ground squirrels in the cecum lumen. Our study presents another step toward developing ground squirrels as a model for studying the interaction between the microbiota and host inflammation.<b>NEW & NOTEWORTHY</b> Disruptions of gut microbiota can lead to inflammation, resulting in weight gain. Inflammation can be treated with budesonide, but how budesonide affects gut microbiota is unclear. Thirteen-lined ground squirrels experience low-grade gut inflammation during prehibernation fattening, which compares with human inflammation-weight gain mechanisms. We showed that budesonide treatment decreased microbiome diversity and lead to a shift in community in the cecum lumen. Our study supports developing ground squirrels as a model for studying microbiome-inflammation interactions.