Abstract
Several factors are linked to the pathophysiology of autism spectrum disorders (ASD); however, the molecular mechanisms of the condition remain unknown. As intestinal problems and gut microbiota dysbiosis are associated with ASD development and severity, recent studies have focused on elucidating the microbiota-gut-brain axis’ involvement. This study aims to explore mechanisms through which gut microbiota might influence ASD. Briefly, we depleted the microbiota of conventional male BALB/cAnNCrl (Balb/c) and C57BL/6J (BL/6) mice prior to human fecal microbiota transplantation (hFMT) with samples from children with ASD or their neurotypical siblings. We found mouse strain-specific responses to ASD hFMT. Notably, Balb/c mice exhibit decreased exploratory and social behavior, and show evidence of intestinal, systemic, and central inflammation accompanied with metabolic shifts. BL/6 mice show less changes after hFMT. Our results reveal that gut microbiota alone induce changes in ASD-like behavior, and highlight the importance of mouse strain selection when investigating multifactorial conditions like ASD.
| Original language | English |
|---|---|
| Article number | 2447822 |
| Journal | Gut Microbes |
| Volume | 17 |
| Issue number | 1 |
| Early online date | 7 Jan 2025 |
| DOIs | |
| Publication status | Published - 2025 |
Bibliographical note
Publisher Copyright:© 2025 The Author(s). Published with license by Taylor & Francis Group, LLC.
Funding
This study was funded by the European Commission through the Horizon 2020 program [H2020-SC1-BHC-03-2018] with project [ID 825033]. We are grateful to the children and families who contributed time and samples for this study. We thank Giulio Corrivetti, Carmela Bravaccio, Maria Pia Riccio from ASL Salerno for the family\u2019s recruitment; Jacopo Troisi, Illaria Tamburo, Carminia Ingenito from EBRIS for their help and providing the facilities to process the fecal samples from the donors; the Maat Pharma team (https://www.maatpharma.com/) for providing the equipment to collect and process the fecal samples from the children. We also thank the staff at the Utrecht Metabolism Expertise Centre (Utrecht University) for support in the acquisition and analysis of metabolomics data. For the 16S rRNA gene sequencing analysis of murine samples, we thank the @BRIDGe platform, Marie-No\u00EBlle Rossignol and Deborah Jardet (GABI, INRAE, AgroParisTech, Paris Saclay-University, Jouy-en-Josas). We also want to thank Himanshu Kumar and Ioannis Kostopoulos (Danone Nutricia Research, Utrecht) for providing the 16S rRNA gene sequencing raw data of the fecal samples from donors.
| Funders | Funder number |
|---|---|
| MaaT Pharma | |
| Danone Nutricia Research, Utrecht | |
| Himanshu Kumar and Ioannis Kostopoulos | |
| Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement | |
| European Commission | |
| Universiteit Utrecht | |
| Horizon 2020 Framework Programme | H2020-SC1-BHC-03-2018, 825033 |
Keywords
- autism spectrum disorders
- Fecal microbiota transplantation
- gut-brain axis
- humanized mouse model
