Stressor-induced immunomodulation is attenuated by prebiotics and milk oligosaccharides: Role of the colonic metabolome

Prebiotics and milk oligosaccharides have been shown to impact the gut microbiota and attenuate many effects of stressor exposure. We tested whether the social disruption (SDR) stressor 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 were placed on one of the experimental diets for 14d: a) SL [2.2 g/kg], b) GOS + PDX [15 g/kg each] + SL [2.2 g/kg] or c) Control [cellulose as fiber source]. Mice were then exposed to the SDR stressor, entailing repeated social defeat for 2 h per day for 6 days, or left undisturbed as controls. Metabolites in the colonic contents were assessed using LC/MS. Stressor- exposed mice fed the control diet showed significant differences in 116 of 529 colonic metabolites, compared to controls. This was partly due to significant reductions in dipeptides and amino acids, and significant increases in nucleotides and sphingolipids. Stressor-exposed mice fed diets enriched with prebiotics or milk oligosaccharides showed similar changes in these metabolites, but also showed significant increases in polyunsaturated fatty acids and endocannabinoids, compared with the non-stress groups. Stressor-induced increases in inflammatory cytokines tended to be attenuated by prebiotics or milk oligosaccharides. This study demonstrates that dietary prebiotics and milk oligosaccharides can impact the colonic metabolome to potentially attenuate stressor-induced immunomodulation.