@article{cb234b5608904fed969ea75ed9ce197f,
title = "Maternal gut microbiota mediate intergenerational effects of high-fat diet on descendant 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.",
keywords = "CP: Microbiology, CP: Neuroscience, DOHaD, Limosilactobacillus reuteri, intergenerational, maternal diet, microbiome, neurodevelopment, probiotics, social behavior",
author = "{Di Ges{\`u}}, {Claudia M.} and Matz, {Lisa M.} and Bolding, {Ian J.} and Robert Fultz and Hoffman, {Kristi L.} and Gammazza, {Antonella Marino} and Petrosino, {Joseph F.} and Buffington, {Shelly A.}",
note = "Funding Information: We would like to acknowledge the UTMB Animal Resource Center and Germ-Free Mouse Facility (supported by the Sealy Center for Microbiome Research) and Dr. Maki Wakamiya, as well as the Baylor College of Medicine Gnotobiotic Core Facility (supported in part by PHS grant P30DK056338) and Dr. Stephanie W. Fowler for providing excellent care for the mice involved in this study, Dr. Heidi Spratt for statistical consultation, and The Alkek Center for Metagenomics and Microbiome Research at Baylor College of Medicine for RNA extraction and 16S rRNA gene amplicon sequencing. Body composition analyses were performed in the UTMB Center for Addiction Research (CAR) Rodent In Vivo Assessment (RIVA) Core. Figures were created using Adobe Illustrator and schematics using BioRender (BioRender.com; publication and licensing rights agreement QR23HLBKNP). Research reported in this publication was supported with funding from the National Institutes of Health (R01HD109095), the Brain & Behavior Research Foundation (NARSAD Young Investigator Grant 28298), the Scott-Gentle Foundation, the UTMB Institute for Human Infections and Immunity, and the Gulf Coast Center for Precision Environmental Health, via Center Core Grant from the National Institute for Environmental Health Sciences of the National Institutes of Health (NIH) under award no. P30ES030285 (the content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH), to S.A.B. Salary support for L.M.M. during a portion of the project was provided by NIH 1T32AG067952-01 (UTMB Mitchell Center for Neurodegenerative Diseases). Conceptualization and design, C.M.D. L.M.M. and S.A.B.; acquisition and analysis of data, C.M.D. L.M.M. R.F. I.J.B. K.L.H. J.F.P. and S.A.B.; writing – review & editing, C.M.D. L.M.M. K.L.H. A.M.G. J.F.P. and S.A.B. S.A.B. is an inventor on a patent granted to Baylor College of Medicine related to the use of Limosilactobacillus reuteri for treating disorders characterized by social dysfunction (US Patent No. 11135252). The authors declare no other competing interests. We support inclusive, diverse, and equitable conduct of research. Funding Information: We would like to acknowledge the UTMB Animal Resource Center and Germ-Free Mouse Facility (supported by the Sealy Center for Microbiome Research ) and Dr. Maki Wakamiya, as well as the Baylor College of Medicine Gnotobiotic Core Facility (supported in part by PHS grant P30DK056338 ) and Dr. Stephanie W. Fowler for providing excellent care for the mice involved in this study, Dr. Heidi Spratt for statistical consultation, and The Alkek Center for Metagenomics and Microbiome Research at Baylor College of Medicine for RNA extraction and 16S rRNA gene amplicon sequencing. Body composition analyses were performed in the UTMB Center for Addiction Research (CAR) Rodent In Vivo Assessment (RIVA) Core. Figures were created using Adobe Illustrator and schematics using BioRender ( BioRender.com ; publication and licensing rights agreement QR23HLBKNP). Research reported in this publication was supported with funding from the National Institutes of Health ( R01HD109095 ), the Brain & Behavior Research Foundation (NARSAD Young Investigator Grant 28298 ), the Scott-Gentle Foundation , the UTMB Institute for Human Infections and Immunity , and the Gulf Coast Center for Precision Environmental Health , via Center Core Grant from the National Institute for Environmental Health Sciences of the National Institutes of Health (NIH) under award no. P30ES030285 (the content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH), to S.A.B. Salary support for L.M.M. during a portion of the project was provided by NIH 1T32AG067952-01 (UTMB Mitchell Center for Neurodegenerative Diseases). Publisher Copyright: {\textcopyright} 2022 The Author(s)",
year = "2022",
month = oct,
day = "11",
doi = "10.1016/j.celrep.2022.111461",
language = "English (US)",
volume = "41",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "2",
}