Brain, behavior, & immunity - healthSep 14, 2026

Sex and type of stress affect behavior, immune response, and gut bacteria in pubertal mice

Gut-Brain Axis Weekly Brief ↗PubMed ↗DOI ↗

Updated Sep 15, 2026

Abstract

100 CD-1 mice were subjected to chronic unpredictable stress or sleep disruption during puberty, revealing distinct behavioral and immune responses.

Females displayed increased open-arm exploration, while sleep disruption reduced this behavior.
Chronic unpredictable stress for 14 days decreased center activity in the open field.
Increased immobility was observed in males following sleep disruption during the forced swim test.
Cytokine levels varied significantly, with IL-22 elevated across stress conditions and IL-17A highest after 28-day chronic unpredictable stress.
NLRP3 and CASP1 mRNA expression increased in the prefrontal cortex of sleep-disrupted males, while females showed reduced NFκB1 expression after 28-day chronic unpredictable stress.
Microbiome analysis indicated substantial changes due to sleep disruption and chronic unpredictable stress, with reductions in beneficial bacteria and increases in stress-associated genera.

Simplified

Puberty is a critical developmental period marked by heightened vulnerability to stress. Exposure to pubertal stress can have lasting effects on behaviour, immune function, and the gut-brain axis. The NLRP3 inflammasome and gut microbiome are key regulators of neuroinflammation, yet their roles across distinct pubertal stress paradigms remain unclear. This study compared behavioural, immune, and microbial outcomes in 100 CD-1 mice following chronic unpredictable stress (CUS; 14 or 28 days) or 7-day sleep disruption (SD) in pubertal males and females. Behavioural testing revealed stressor- and sex-specific effects: females spent more time in the open arms of the elevated plus maze, SD reduced open-arm exploration, 14-day CUS reduced centre activity in the open field, and SD increased immobility in the forced swim test. Plasma cytokines showed divergent patterns, with IL-22 elevated across stress conditions and IL-17A highest following 28-day CUS and in females overall. In the prefrontal cortex, SD males exhibited increased NLRP3 and CASP1 mRNA expression, whereas 28-day CUS females showed reduced NFκB1, and NFκB2 expression was elevated in stress-exposed males. In the hippocampus, 28-day CUS females demonstrated coordinated reductions in NFκB1, NLRP3, and CASP1 expression. Microbiome analyses indicated that SD and 14-day CUS produced the most substantial alterations, characterized by reductions in short-chain fatty acid-producing taxa (Ligilactobacillus, Acetatifactor, Christensenella) and enrichment of stress-associated genera (Flintibacter, Oscillospiraceae). Together, these findings indicate that stressor type and sex differentially shape behavioural, neuroimmune, and microbial profiles during puberty, with sleep disruption exerting particularly strong effects on behavioural and gut-immune regulation.

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Sex and type of stress affect behavior, immune response, and gut bacteria in pubertal mice

Abstract

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