4.7 Article

Mom's diet matters: Maternal prebiotic intake in mice reduces anxiety and alters brain gene expression and the fecal microbiome in offspring

Journal

BRAIN BEHAVIOR AND IMMUNITY
Volume 91, Issue -, Pages 230-244

Publisher

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbi.2020.09.034

Keywords

Galacto-oligosaccharide; Short-chain fatty acids; Early life; NMDAR; Prefrontal cortex; Hippocampus; Perinatal; 16S sequencing; Gut-brain axis; NMR

Funding

  1. Rhodes Trust
  2. Biotechnology, Biological Sciences, Research Council (BBSRC) UK [BB/I006311/1]
  3. Internal Oxford University funds
  4. Wellcome Trust [203141/Z/16/Z]
  5. BBSRC [BB/N010035/1, BB/I006311/1] Funding Source: UKRI

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This study demonstrated that maternal intake of galacto-oligosaccharides during pregnancy and lactation may have an impact on offspring brain and behavior. In mice experiments, it was found that maternal B-GOS supplementation could increase exploratory behavior in offspring and affect brain gene expression and gut microbiome composition.
Compelling evidence links enteric microbes to brain function and behavior. Galacto-oligosaccharide prebiotics have been shown to modulate the composition of gut flora and induce metabolic, neurochemical, and behavioral changes in adult rodents. Despite the brain being most susceptible to environmental factors, such as nutrients and toxins, during the earliest stages of development, it is unknown whether maternal prebiotic supplementation during gestation and lactation influences the offspring gut microbiome, brain, or behavior. The aim of this study was to test whether maternal galacto-oligosaccharide intake during pregnancy and lactation alters the brain and behavior in nave and endotoxin-challenged offspring. CD1 female mice received either normal drinking water or water supplemented with Bimuno (R) galacto-oligosaccharides (B-GOS) during gestation and suckling. Offspring behavior was tested at weaning age or adulthood, and a cross-foster design was employed in a separate cohort to differentiate between effects of prenatal and postnatal maternal B-GOS intake. Lipopolysaccharide was also administered to pups at postnatal day 9 to determine whether maternal B-GOS influences the neurobiological and behavioral effects of a neonatal proinflammatory challenge in adulthood. Fecal microbiome composition and metabolites were analyzed to explore potential relationships between the maternal microbiome, the offspring gut microbiome, and the offspring brain and behavior. Maternal B-GOS supplementation increased exploratory behavior and reduced expression of hippocampal glutamate receptor genes in young, weaning-age offspring. In addition, postnatal, but not prenatal, B-GOS supplementation increased fecal butyrate and propionate levels. Finally, in adult offspring, perinatal B-GOS intake increased cortical glutamate receptor subunits in females, increased social preference, and reduced anxiety. We provide novel and comprehensive evidence for the influence of maternal prebiotic intake on offspring behavior, brain gene expression, and gut microbiome composition in mice.

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