Effect of early life supplementation of non-digestible oligosaccharides on brain development and behaviour in healthy mice

Background: Non-digestible oligosaccharides have beneficial effects by modulating the intestinal microbiota composition and are known to have immunomodulatory properties. Recent studies have shown that changes in microbiota composition also affect brain development and function. So far most of these studies have been performed in germ-free mice or via antibiotic-induced alteration of microbiome composition [1]. In an early life dietary intervention study with the non-digestible oligosaccharides short chain galacto- and long chain fructo-oligosaccharides (scGOS:lcFOS), we investigated the effects of changes in microbiome metabolism on the brain development and function in healthy BALB/c mice. Method: Dietary supplementation with or without 3% sc- GOS:lcFOS (9:1) was tested in male BALB/c mice starting from day of birth (n = 10 per group). At postnatal day 10 ultrasonic vocalization (UV) was examined. Anxiety-like and stereotypic behaviours were longitudinally studied by conducting marble burying and self-grooming tests. Additionally, social behaviour was studied in adulthood. Monoamine levels and mRNA expression of 5-hydroxytryptamine 1A (5-HT1A) receptor, astrocytic glial fibrillary acidic protein (GFAP), microglial integrin alpha M (ITGAM), and brain-derived neurotrophic factor (BDNF) in the prefrontal cortex (PFC) were assessed. Caecal short-chain fatty acids (SCFA, butyric acid and valeric acid) and branched chain fatty acids (BCFA, isobutyric acid and isovaleric acid) levels were determined and, since SCFA are potent histone deacetylase (HDAC) inhibitors, colonic HDAC activity was assessed. Statistical significance was determined by unpaired t-tests and in case the data was not normally distributed the Mann-Whitney nonparametric test was used, P