Prebiotics and anti-inflammatory drug alter tight junction protein expression in fattening ground squirrels and outbred mice

Obesity and rapid adiposity are triggered by dysbiosis of gut microbiota that leads to subclinical intestinal inflammation and loss of gut barrier integrity. We have previously shown that the gut-specific nonsteroidal anti-inflammatory drug (NSAID) mesalazine is sufficient to decrease inflammatory cytokines in the gut and adipose tissue, but not to prevent adiposity in 13-lined ground squirrels (Ictidomys tridecemlineatus). We hypothesize that mesalazine alone is not sufficient to prevent barrier dysfunction and changes to mucosal architecture. We thus examined the effects of mesalazine, prebiotics, or both on villus height and tight junction protein expression in ground squirrels and outbred mice. Mesalazine increased villus height in mice but not ground squirrels. Combined treatment with mesalazine and prebiotics increased occludin, but not E-cadherin, expression in ground squirrels after 4 weeks. No treatment altered expression of occludin or E-cadherin in outbred mice. This experiment highlights species differences in the effects of these treatments on barrier integrity. Comparison to human studies is needed to determine whether ground squirrels or outbred mice better mimic the human response. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.