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ObjectiveRecent studies have provided insights into the gut microbiota in autism spectrum disorder (ASD); however, these studies were restricted owing to limited sampling at the unitary stage of childhood. Herein, we aimed to reveal developmental characteristics of gut microbiota in a large cohort of subjects with ASD combined with interindividual factors impacting gut microbiota.DesignA large cohort of 773 subjects with ASD (aged 16 months to 19 years), 429 neurotypical (NT) development subjects (aged 11 months to 15 years) were emolyed to determine the dynamics change of gut microbiota across different ages using 16S rRNA sequencing.ResultIn subjects with ASD, we observed a distinct but progressive deviation in the development of gut microbiota characterised by persistently decreased alpha diversity, early unsustainable immature microbiota, altered aboudance of 20 operational taxonomic units (OTUs), decreased taxon detection rate and 325 deregulated microbial metabolic functions with age-dependent patterns. We further revealed microbial relationships that have changed extensively in ASD before 3 years of age, which were associated with the severity of behaviour, sleep and GI symptoms in the ASD group. This analysis demonstrated that a signature of the combination of 2 OTUs, Veillonella and Enterobacteriaceae, and 17 microbial metabolic functions efficiently discriminated ASD from NT subjects in both the discovery (area under the curve (AUC)=0.86), and validation 1 (AUC=0.78), 2 (AUC=0.82) and 3 (AUC=0.67) sets.ConclusionOur large cohort combined with clinical symptom analysis highlights the key regulator of gut microbiota in the pathogenesis of ASD and emphasises the importance of monitoring and targeting the gut microbiome in future clinical applications of ASD.

Human longevity has a strong familial and genetic component. Dynamic characteristics of the gut microbiome during aging associated with longevity, neural, and immune function remained unknown. Here, we aim to reveal the synergistic changes in gut microbiome associated with decline in neural and immune system with aging and further obtain insights into the establishment of microbiome homeostasis that can benefit human longevity. Based on 16S rRNA and metagenomics sequencing data for 32 longevity families including three generations, centenarians, elderly, and young groups, we found centenarians showed increased diversity of gut microbiota, severely damaged connection among bacteria, depleted in microbial-associated essential amino acid function, and increased abundance of anti-inflammatory bacteria in comparison to young and elderly groups. Some potential probiotic species, such as Desulfovibrio piger, Gordonibacter pamelaeae, Odoribacter splanchnicus, and Ruminococcaceae bacterium D5 were enriched with aging, which might possibly support health maintenance. The level of Amyloid-β (Aβ) and brain-derived neurotrophic factor (BDNF) related to neural function showed increased and decreased with aging, respectively. The elevated level of inflammatory factors was observed in centenarians compared with young and elderly groups. The enriched Bacteroides fragilis in centenarians might promote longevity through up-regulating anti-inflammatory factor IL-10 expression to mediate the critical balance between health and disease. Impressively, the associated analysis for gut microbiota with the level of Aβ, BDNF, and inflammatory factors suggests Bifidobacterium pseudocatenulatum could be a particularly beneficial bacteria in the improvement of impaired neural and immune function. Our results provide a rationale for targeting the gut microbiome in future clinical applications of aging-related diseases and extending life span. Abbreviations : 16S rRNA : 16S ribosomal RNA; MAGs : Metagenome-assembled genomes; ASVs : Amplicon sequence variants; DNA : Deoxyribonucleic acid; FDR : False discovery rate: KEGG : Kyoto Encyclopedia of Genes and Genomes; PCoA : Principal coordinates analysis; PCR : Polymerase chain reaction; PICRUSt : Phylogenetic Investigation of Communities by Reconstruction of Unobserved States; Aβ : Amyloid-β (Aβ); BDNF : Brain-derived neurotrophic factor