Early-life differences in the gut microbiota composition and functionality of infants at elevated likelihood of developing autism spectrum disorder.
Journal
Translational psychiatry
ISSN: 2158-3188
Titre abrégé: Transl Psychiatry
Pays: United States
ID NLM: 101562664
Informations de publication
Date de publication:
13 Jul 2023
13 Jul 2023
Historique:
received:
19
06
2023
accepted:
30
06
2023
revised:
29
06
2023
medline:
17
7
2023
pubmed:
14
7
2023
entrez:
14
7
2023
Statut:
epublish
Résumé
Evidence from cross-sectional human studies, and preliminary microbial-based intervention studies, have implicated the microbiota-gut-brain axis in the neurobiology of autism spectrum disorder (ASD). Using a prospective longitudinal study design, we investigated the developmental profile of the fecal microbiota and metabolome in infants with (n = 16) and without (n = 19) a family history of ASD across the first 36 months of life. In addition, the general developmental levels of infants were evaluated using the Mullen Scales of Early Learning (MSEL) test at 5 and 36 months of age, and with ADOS-2 at 36 months of age. At 5 months of age, infants at elevated-likelihood of ASD (EL) harbored less Bifidobacterium and more Clostridium and Klebsiella species compared to the low-likelihood infants (LL). Untargeted metabolic profiling highlighted that LL infants excreted a greater amount of fecal γ-aminobutyric acid (GABA) at 5 months, which progressively declined with age. Similar age-dependent patterns were not observed in the EL group, with GABA being consistently low across all timepoints. Integrated microbiome-metabolome analysis showed a positive correlation between GABA and Bifidobacterium species and negative associations with Clostridium species. In vitro experiments supported these observations demonstrating that bifidobacteria can produce GABA while clostridia can consume it. At the behavioral level, there were no significant differences between the EL and LL groups at 5 months. However, at 36 months of age, the EL group had significantly lower MSEL and ADOS-2 scores compared to the LL group. Taken together, the present results reveal early life alterations in gut microbiota composition and functionality in infants at elevated-likelihood of ASD. These changes occur before any behavioral impairments can be detected, supporting a possible role for the gut microbiota in emerging behavioral variability later in life.
Identifiants
pubmed: 37443359
doi: 10.1038/s41398-023-02556-6
pii: 10.1038/s41398-023-02556-6
pmc: PMC10344877
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
257Subventions
Organisme : Hjärnfonden (Swedish Brain Foundation)
ID : FO2020-0088, FO2022-0199
Organisme : RCUK | Biotechnology and Biological Sciences Research Council (BBSRC)
ID : BB/W00139X/1, BB/N005953/1
Organisme : RCUK | Medical Research Council (MRC)
ID : BB/W00139X/1, BB/N005953/1
Informations de copyright
© 2023. The Author(s).
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