Maternal Gut Microbiota Mediate Intergenerational Effects of High-Fat Diet on Descendant Social Behavior

Authors

Claudia M Di Gesù
Lisa M Matz
Ian J Bolding
Robert Fultz
Kristi L Hoffman
Antonella Marino Gammazza
Joseph F Petrosino
Shelly A Buffington

Publication Date

10-11-2022

Journal

Cell Reports

DOI

10.1016/j.celrep.2022.111461

PMID

36223744

PMCID

PMC9597666

PubMedCentral® Posted Date

10-11-2022

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

Animals, Diet, High-Fat, Dysbiosis, Female, Gastrointestinal Microbiome, Male, Mice, Pregnancy, Social Behavior

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.

Comments

This article has been corrected. See Cell Rep. 2023 May 2;42(5):112498.