Sex differences in the effects of early‐life probiotic treatment on TNBS‐induced colitis in rats

Abstract

We tested the effects of early‐life probiotic treatment on the induction of colitis in female and male adult rats. Rat pups were fed an aqueous solution of Lactobacillus rhamnosus (from day 4 to day 30). Feces were collected for microbial analysis. Colitis was induced at day 85. Seven days later rats were graded for histological damage in colon, and samples of mesenteric lymph node (MLN) and peritoneal exudate cells were analyzed. Female rats developed slightly less severe symptoms of colitis than males, whereas early‐life probiotic treatment had a more pronounced effect on males in nearly every analyzed parameter. Namely, it increased fecal bacterial diversity and ameliorated colon tissue damage, as well as increased percentage of resident peritoneal macrophages (CD163+), decreased peritoneal monocyte (HIS48+CD43+) influx, reduced production of IFNγ and IL10 by MLN cells, attenuated NO production in stimulated peritoneal macrophages and unstimulated MLN cells of male rats. Our findings reveal that effects of probiotic treatment are sex‐specific to an extent. While microbial diversity was impacted by probiotic treatment in both sexes at an early age, the effect was more pronounced in young males, and it lasted to their adulthood. The change in microbial diversity correlated with improved outcome of TNBS‐induced colitis, confirming the importance of microbiota for local inflammatory processes. It remains to be elucidated whether the sex differences in the effect of probiotic treatment on development of colitis may be a consequence of sex differences in early‐life microbial diversity and severity of colitis symptoms in untreated rats.