Gene variations in autism spectrum disorder are associated with alteration of gut microbiota, metabolites and cytokines.

The genetic variations and dysbiosis of gut microbiota are associated with ASD. However, the role of the microbiota in the etiology of ASD in terms of host genetic susceptibility remains unclear. This study aims to systematically explore the interplay between host genetic variation and gut microbiota in ASD children. Whole-exon sequencing was applied to 26 ASD children and 26 matched controls to identify the single nucleotide variations (SNVs) in ASD. Our previous study revealed alteration in gut microbiota and disorder of metabolism activity in ASD for this cohort. Systematic bioinformatic analyses were further performed to identify associations between SNVs and gut microbiota, as well as their metabolites. The ASD SNVs were significantly enriched in genes associated with innate immune response, protein glycosylation process, and retrograde axonal transport. These SNVs were also correlated with the microbiome composition and a broad aspect of microbial functions, especially metabolism. Additionally, the abundance of metabolites involved in the metabolic network of neurotransmitters was inferred to be causally related to specific SNVs and microbes. Furthermore, our data suggested that the interaction of host genetics and gut microbes may play a crucial role in the immune and metabolism homeostasis of ASD. This study may provide valuable clues to investigate the interaction of host genetic variations and gut microbiota in the pathogenesis of ASD.

Altered gut microbial profile is associated with abnormal metabolism activity of Autism Spectrum Disorder.

Autism Spectrum Disorder (ASD) is a severe neurodevelopmental disorder. To enhance the understanding of the gut microbiota structure in ASD children at different ages as well as the relationship between gut microbiota and fecal metabolites, we first used the 16S rRNA sequencing to evaluate the gut microbial population in a cohort of 143 children aged 2-13 years old. We found that the α-diversity of ASD group showed no significant change with age, while the TD group showed increased α-diversity with age, which indicates that the compositional development of the gut microbiota in ASD varies at different ages in ways that are not consistent with TD group. Recent studies have shown that chronic constipation is one of the most commonly obvious gastrointestinal (GI) symptoms along with ASD core symptoms. To further investigate the potential interaction effects between ASD and GI symptoms, the 30 C-ASD and their aged-matched TD were picked out to perform metagenomics analysis. We observed that C-ASD group displayed decreased diversity, depletion of species of Sutterella, Prevotella, and Bacteroides as well as dysregulation of associated metabolism activities, which may involve in the pathogenesis of C-ASD. Consistent with metagenomic analysis, liquid chromatography-mass spectrometry (LC/MS) revealed some of the differential metabolites between C-ASD and TD group were involved in the metabolic network of neurotransmitters including serotonin, dopamine, histidine, and GABA. Furthermore, we found these differences in metabolites were associated with altered abundance of specific bacteria. The study suggested possible future modalities for ASD intervention through targeting the specific bacteria associated with neurotransmitter metabolism.

Acute Sleep-Wake Cycle Shift Results in Community Alteration of Human Gut Microbiome.

Disturbances of sleep and the underlying circadian rhythm are related to many human diseases, such as obesity, diabetes, cardiovascular disorders, and cognitive impairments. Dysbiosis of the gut microbiome has also been reported to be associated with the pathologies of these diseases. Therefore, we proposed that disturbed sleep may regulate gut microbiota homeostasis. In this study, we mimicked the sleep-wake cycle shift, one typical type of circadian rhythm disturbances in young people, in recruited subjects. We used 16S rRNA gene amplicon sequencing to define microbial taxa from their fecal samples. Although the relative abundances of the microbes were not significantly altered, the functional-profile analysis of gut microbiota revealed functions enriched during the sleep-wake cycle shift. In addition, the microbial networks were quite distinct among baseline, shift, and recovery stages. These results suggest that an acute sleep-wake cycle shift may exert a limited influence on the gut microbiome, mainly including the functional profiles of the microbes and the microbial relationships within the microbial community.IMPORTANCE Circadian rhythm misalignment due to social jet lag, shift work, early morning starts, and delayed bedtimes is becoming common in our modern society. Disturbances of sleep and the underlying circadian rhythms are related to multiple human diseases, such as obesity, diabetes, cardiovascular disorders, and cognitive impairments. Given the crucial role of microbiota in the same pathologies as are caused by sleep disturbance, how the gut microbiota is affected by sleep is of increasing interest. The results of this study indicate that the acute circadian rhythm disturbance caused by sleep-wake shifts affect the human gut microbiota, especially the functional profiles of gut microbes and interactions among them. Further experiments with a longer-time-scale intervention and larger sample size are needed to assess the effects of chronic circadian rhythm disruption on the gut microbiome and to guide possible microbial therapies for clinical intervention in the related diseases.