Prebiotics and milk oligosaccharides affect colonic metabolome and stressor‐induced immunomodulation in mice

There are extensive bidirectional interactions between the gut microbiota and the central nervous system (CNS). Dietary interventions that impact the microbiota, such as prebiotics and milk oligosaccharides, have been shown to reduce risk of many deleterious effects of stressor exposure. However, the mechanisms through which the microbiota influence the host are not well understood. We tested whether exposure to a social stressor, called social disruption (SDR), results in metabolomic changes in the colon, and whether prebiotics (blend of galactooligosaccharides (GOS) and polydextrose (PDX)) and/or milk oligosaccharide sialyllactose (Lacprodan SAL‐10 ® , SL) support a normal metabolome in the presence of stress. Male mice (postnatal day (P) 48–64) were placed on one of the experimental diets for 14d: a) SL [2.2g/kg], b) GOS+PDX [15g/kg each] + SL [2.2g/kg] or c) Control [cellulose as fiber source]. Mice were then randomly assigned to either the non‐stressed control group or to the Social Disruption Stressor (SDR Stressor) condition. SDR stressor entails repeated social defeat for 2 hrs per day on 6 consecutive days. Metabolites in the colonic contents were then assessed using LC/MS, while serum cytokine levels were assessed by ELISA. Mice fed a control diet and exposed to the stressor showed significant differences in 116 out of 529 detected metabolites, compared to control diet non‐stressed mice. This was partly due to significant reductions in dipeptides and amino acids, as well as significant increases in nucleotides and sphingolipids. Interestingly, stress‐exposed mice fed diets enriched with prebiotics (either a combination of GOS, PDX, and SL or SL alone) showed similar changes in dipeptides, nucleotides, and sphingolipids, but also showed increases in polyunsaturated fatty acids and endocannabinoids, as compared with the non‐stress groups. Polyunsaturated fatty acids and endocannabinoids can have anti‐inflammatory effects, thus we determined whether the experimental diets would attenuate stressor‐induced increases in inflammatory cytokines. Serum IL‐6 and IL‐1β were significantly increased in stressor‐exposed mice, but this effect tended to be attenuated in mice fed both treatment diets (diet × stress condition interactions, p‐values = 0.081 and 0.056, respectively). This study demonstrates that dietary prebiotics and milk oligosaccharides can impact the colonic metabolome to potentially attenuate stressor‐induced immunomodulation. Support or Funding Information Supported by Mead Johnson Nutrition