Early-life differences in the gut microbiota composition and functionality of infants at elevated likelihood of developing autism spectrum disorder.

Publication date: Jul 13, 2023

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.

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Concepts Keywords
Autism Age
Bifidobacteria Asd
Klebsiella Behavioral
Months Composition
Neurobiology Differences


Type Source Name
disease MESH autism spectrum disorder
drug DRUGBANK gamma-Aminobutyric acid
disease MESH sleep disorders
disease MESH epilepsy
drug DRUGBANK Vancomycin
disease MESH autism
disease MESH Neurodevelopmental Disorders
drug DRUGBANK Coenzyme M
drug DRUGBANK Sulfate ion
disease MESH etiology
disease MESH syndromes
drug DRUGBANK Methionine
drug DRUGBANK Etoperidone
drug DRUGBANK Pidolic Acid
drug DRUGBANK Putrescine
drug DRUGBANK Spermidine
drug DRUGBANK Dextrose unspecified form
drug DRUGBANK Monopotassium phosphate
drug DRUGBANK Dipotassium phosphate
drug DRUGBANK Magnesium sulfate
drug DRUGBANK L-Cysteine
drug DRUGBANK Phosphate ion
disease MESH preterm birth
drug DRUGBANK Formic Acid
drug DRUGBANK Fructose
drug DRUGBANK Galactose
drug DRUGBANK Proline
drug DRUGBANK Valproic Acid
drug DRUGBANK Butyric Acid
drug DRUGBANK L-Isoleucine
drug DRUGBANK Succinic acid
drug DRUGBANK L-Tryptophan
drug DRUGBANK Maltose
drug DRUGBANK Sarcosine
drug DRUGBANK Acetate ion
disease MESH stroke
drug DRUGBANK Folic Acid
disease MESH inflammation
disease MESH gestational diabetes
disease MESH psychiatric disorders
drug DRUGBANK L-Glutamine
drug DRUGBANK Lactobacillus reuteri
drug DRUGBANK Bifidobacterium longum infantis
drug DRUGBANK Serotonin
drug DRUGBANK Glycine
drug DRUGBANK Isoxaflutole
disease MESH complications
drug DRUGBANK Amino acids
disease MESH Avoidant restrictive food intake disorder
drug DRUGBANK Medrysone
drug DRUGBANK Flunarizine
disease MESH brain disorders
drug DRUGBANK Guanosine
drug DRUGBANK Trestolone
drug DRUGBANK Carboxyamidotriazole
disease MESH ADHD
drug DRUGBANK Ammonia
pathway KEGG Purine metabolism
pathway KEGG Tryptophan metabolism

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