ENVIRONMENTAL COMPLEXITY MODULATES THE MICROBIOTA-GUT–BRAIN AXIS DURING EXPERIMENTAL COLITIS

Ulcerative colitis (UC), a chronic inflammatory bowel disease, is frequently associated with mental health disturbances. These perturbations can be worsened by chronic stress. Environmental complexity (EC) has been reported to reduce stress and inflammation in rodents; therefore, we hypothesized that EC might mitigate the behavioral and neurobiological consequences of experimental colitis. Female mice were housed for eight weeks under either standard environment (SE) or environmental complexity (EC) conditions, and subgroups were treated with dextran sulphate sodium (DSS) to induce colitis. Behavioral assessments, inflammatory readouts, and analyses of the gut microbiome and metabolome were performed.
DSS-treated females housed in EC exhibited more severe disease symptoms compared to SE counterparts. Regardless of housing, DSS treatment reduced locomotor activity, increased anxiety-like behavior, and decreased social interactions. DSS-treated animals also showed elevated levels of innate immune cells in colon, brain, and blood, indicating inflammation along the gut–brain axis. EC-housed animals appeared to have higher basal stress and were more susceptible to systemic inflammation. Moreover, EC enhanced colitis-induced metabolite alterations across the gut–brain axis and modified colitis-driven changes to the gastrointestinal microbiome.
In conclusion, environmental complexity unexpectedly exacerbated inflammation and disease severity in female mice, suggesting that EC may heighten vulnerability to stress-related and inflammatory processes through modulation of the microbiota-gut-brain axis.