Sex-dependent responses to milk and Lacticaseibacillus casei BL23 in a mouse model of colitis

This study aimed to determine the extent that milk and probiotic Lacticaseibacillus casei, combined and separately, affect intestinal responses in a mouse model of inflammatory bowel disease. Female (n=42) and male (n=44) C57BL/6J mice were fed ultra-high temperature 2% fat milk, nutrient-free buffer (PBS), or 7x107 L. casei BL23 cells in either delivery matrix (BL23-milk or BL23-PBS) daily for 17 days. Dextran Sodium Sulfate (DSS, 3% w/v) was added to the drinking water to induce colitis 4 days after the start of BL23 feeding and sustained for the subsequent 5 days after which recovery was monitored. Females developed a more severe colitis, greater weight loss, and a higher mortality rate compared with male mice. Although all females fed BL23-PBS survived DSS treatment, administration of milk (with and without BL23) improved mouse weight recovery that was comparable to healthy controls. Among the males, only mice given milk exhibited an improved weight recovery and only mice given BL23-milk had recovered ion transport across the colon similar to the healthy controls. The microbial composition between female and male mice were distinct according to both alpha and beta diversity metrics. The microbial composition among male mice were driven by the consumption of DSS and BL23 or milk did not have a significant effect. However, the microbial composition of milk and BL23-milk groups differed from both sham and PBS groups among female mice. The relative abundance of many bacterial taxa within the Clostridiales order were negatively correlated with the mRNA expression of both pro- and anti-inflammatory cytokines, but positively correlated with the expression of tight junction protein, occludin. Variations in the effects of BL23 between delivery matrices and mouse sex support ongoing efforts focused on understanding how the food delivery matrix affects probiotic function in the gastrointestinal tract.