Maternal gut microbiota mediate intergenerational effects of high-fat diet on descendant social behavior

Limosilactobacillus reuteri Male 0301 basic medicine 570 Medical Sciences QH301-705.5 610 microbiome Social and Behavioral Sciences Diet, High-Fat Microbiology Article social behavior Mice 03 medical and health sciences Pregnancy Virology Medical Specialties Medicine and Health Sciences maternal diet Animals Biology (General) Social Behavior CP: Microbiology, Gastrointestinal Microbiome, CP: Neuroscience, DOHaD, Limosilactobacillus reuteri, intergenerational, maternal diet, microbiome, neurodevelopment, social behavior, probiotics, Animals, Social Behavior, Dysbiosis, Diet, High-Fat, Pregnancy, Female, Male, Mice 2. Zero hunger neurodevelopment DOHaD CP: Microbiology Life Sciences Diet Gastrointestinal Microbiome High-Fat probiotics Medical Microbiology CP: Neuroscience intergenerational Dysbiosis Female
DOI: 10.1016/j.celrep.2022.111461 Publication Date: 2022-10-11T15:11:37Z
ABSTRACT
Dysbiosis of the maternal gut microbiome during pregnancy is associated with adverse neurodevelopmental outcomes. We previously showed that maternal high-fat diet (MHFD) in mice induces gut dysbiosis, social dysfunction, and underlying synaptic plasticity deficits in male offspring (F1). Here, we reason that, if HFD-mediated changes in maternal gut microbiota drive offspring social deficits, then MHFD-induced dysbiosis in F1 female MHFD offspring would likewise impair F2 social behavior. Metataxonomic sequencing reveals reduced microbial richness among female F1 MHFD offspring. Despite recovery of microbial richness among MHFD-descendant F2 mice, they display social dysfunction. Post-weaning Limosilactobacillus reuteri treatment increases the abundance of short-chain fatty acid-producing taxa and rescues MHFD-descendant F2 social deficits. L. reuteri exerts a sexually dimorphic impact on gut microbiota configuration, increasing discriminant taxa between female cohorts. Collectively, these results show multigenerational impacts of HFD-induced dysbiosis in the maternal lineage and highlight the potential of maternal microbiome-targeted interventions for neurodevelopmental disorders.
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