Colitis reduces active social engagement in mice and is ameliorated by supplementation with human microbiota members

D. Garrett Brown, Michaela Murphy, Roberto Cadeddu, Rickesha Bell, Allison Weis, Tyson Chiaro, Kendra Klag, Jubel Morgan, Hilary Coon, W. Zac Stephens, Marco Bortolato and June L. Round ()
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D. Garrett Brown: University of Utah School of Medicine, Huntsman Cancer Institute, Division of Microbiology and Immunology
Michaela Murphy: University of Utah School of Medicine, Huntsman Cancer Institute, Division of Microbiology and Immunology
Roberto Cadeddu: Department of Pharmacology and Toxicology University of Utah College of Pharmacy
Rickesha Bell: University of Utah School of Medicine, Huntsman Cancer Institute, Division of Microbiology and Immunology
Allison Weis: University of Utah School of Medicine, Huntsman Cancer Institute, Division of Microbiology and Immunology
Tyson Chiaro: University of Utah School of Medicine, Huntsman Cancer Institute, Division of Microbiology and Immunology
Kendra Klag: University of Utah School of Medicine, Huntsman Cancer Institute, Division of Microbiology and Immunology
Jubel Morgan: University of Utah School of Medicine
Hilary Coon: University of Utah School of Medicine
W. Zac Stephens: University of Utah School of Medicine, Huntsman Cancer Institute, Division of Microbiology and Immunology
Marco Bortolato: Department of Pharmacology and Toxicology University of Utah College of Pharmacy
June L. Round: University of Utah School of Medicine, Huntsman Cancer Institute, Division of Microbiology and Immunology

Nature Communications, 2024, vol. 15, issue 1, 1-13

Abstract: Abstract Multiple neurological disorders are associated with gastrointestinal (GI) symptoms, including autism spectrum disorder (ASD). However, it is unclear whether GI distress itself can modify aspects of behavior. Here, we show that mice that experience repeated colitis have impaired active social engagement, as measured by interactions with a foreign mouse, even though signs of colitis were no longer present. We then tested the hypothesis that individuals with ASD harbor a microbiota that might differentially influence GI health by performing microbiota transplantation studies into male germfree animals, followed by induction of colitis. Animals that harbor a microbiota from ASD individuals have worsened gut phenotypes when compared to animals colonized with microbiotas from familial neurotypical (NT) controls. We identify the enrichment of Blautia species in all familial NT controls and observe an association between elevated abundance of Bacteroides uniformis and reductions in intestinal injury. Oral treatment with either of these microbes reduces colon injury in mice. Finally, provision of a Blautia isolate from a NT control ameliorates gut injury-associated active social engagement in mice. Collectively, our data demonstrate that past intestinal distress is associated with changes in active social behavior in mice that can be ameliorated by supplementation of members of the human microbiota.

Date: 2024
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DOI: 10.1038/s41467-024-46733-7

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