Altered gut microbial profile is associated with abnormal metabolism activity of Autism Spectrum Disorder.
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ABSTRACT:
SUBMITTER: Dan Z
PROVIDER: S-EPMC7524265 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Endometrial cancer (EC) is the most prevalent gynecological malignancy, with a higher risk in obese woman, indicating the possibility of gut microbiota involvement in EC progression. However, no direct evidence of a relationship between EC and gut microbiota in humans has been discovered. Here, we performed 16S rRNA sequencing to explore the relationship between dysbiosis of gut microbiota and cancer development in different types of EC patients. The results clearly show the differential profiles of gut microbiota between EC patients and normal participants as well as the association between gut microbiota and EC progression. Targeted metabolomics of plasma revealed an increased level of C16:1 and C20:2, which was positively associated with the abundance of Ruminococcus sp. N15.MGS-57. The higher richness of Ruminococcus sp. N15.MGS-57 in EC subjects not only was positively associated with blood C16:1 and C20:2 but also was negatively correlated with betalain and indole alkaloid biosynthesis. Furthermore, the combined marker panel of gut bacteria, blood metabolites, and clinical indices could distinguish the EC patients under lean and overweight conditions from normal subjects with high accuracy in both discovery and validation sets. In addition, the alteration of tumor microenvironment metabolism of EC was characterized by imaging mass microscopy. Spatial visualization of fatty acids showed that C16:1 and C18:1 obviously accumulate in tumor tissue, and C16:1 may promote EC cell invasion and metastasis through mTOR signaling. The aberrant fecal microbiome, more specifically, Ruminococcus sp. N15.MGS-57 and spatially distributed C16:1 in EC tissues, can be used as a biomarker of clinical features and outcomes and provide a new therapeutic target for clinical treatment. IMPORTANCE A growing number of studies have shown the connection between gut microbiota, obesity, and cancer. However, to our knowledge, the association between gut microbiota and endometrial cancer progression in humans has not been studied. We recruited EC and control individuals as research participants and further subgrouped subjects by body mass index to examine the association between gut microbiota, metabolites, and clinical indices. The higher richness of Ruminococcus sp. N15.MGS-57 in EC subjects was not only positively associated with blood C16:1 but also negatively correlated with betalain and indole alkaloid biosynthesis. Spatial visualization of fatty acids by imaging mass microscopy showed that C16:1 obviously accumulates in tumor tissue, and C16:1 may promote the EC cell invasion and metastasis through mTOR signaling. The aberrant fecal microbiome, more specifically, Ruminococcus sp. N15.MGS-57 and spatially distributed C16:1, can be used as a biomarker of clinical features and outcomes and provide a new therapeutic target for clinical treatment.
| S-EPMC9769730 | biostudies-literature
Project description:Background and Objective: Autism spectrum disorder (ASD) refers to a heterogeneous set of neurodevelopmental disorders with diverse symptom severity and comorbidities. Although alterations in gut microbiota have been reported in individuals with ASD, it remains unclear whether certain microbial pattern is linked to specific symptom or comorbidity in ASD. We aimed to investigate the associations between gut microbiota and the severity of social impairment and cognitive functioning in children with ASD. Methods: A total of 261 age-matched children, including 138 children diagnosed with ASD, 63 with developmental delay or intellectual disability (DD/ID), and 60 typically developing (TD) children, were enrolled from the Shanghai Xinhua Registry. The children with ASD were further classified into two subgroups: 76 children diagnosed with ASD and developmental disorder (ASD+DD) and 62 with ASD only (ASD-only). The gut microbiome of all children was profiled and evaluated by 16S ribosomal RNA sequencing. Results: The gut microbial analyses demonstrated an altered microbial community structure in children with ASD. The alpha diversity indices of the ASD+DD and ASD-only subgroups were significantly lower than the DD/ID or TD groups. At the genus level, we observed a decrease in the relative abundance of Prevotella. Simultaneously, Bacteroides and Faecalibacterium were significantly increased in ASD compared with DD/ID and TD participants. There was a clear correlation between alpha diversity and the Childhood Autism Rating Scale (CARS) total score for all participants, and this correlation was independent of IQ performance. Similar correlations with the CARS total score were observed for genera Bacteroides, Faecalibacterium, and Oscillospira. However, there was no single genus significantly associated with IQ in all participants. Conclusions: Specific alterations in bacterial taxonomic composition and associations with the severity of social impairment and IQ performance were observed in children with ASD or ASD subgroups, when compared with DD/ID or TD groups. These results illustrate that gut microbiota may serve as a promising biomarker for ASD symptoms. Nevertheless, further investigations are warranted.
| S-EPMC8718873 | biostudies-literature
Project description:The cerebral cortex and the cerebellum are spatially remote areas that are connected by complex circuits that link both primary and associative areas. Previous studies have revealed abnormalities in autism spectrum disorder (ASD); however, it is not clear whether cortico-cerebellar connectivity is differentially manifested in the disorder. To explore this issue, we investigated differences in intrinsic cortico-cerebellar functional connectivity between individuals with typical development (TD) and those with ASD. To this end, we used functional magnetic resonance imaging (fMRI) of 708 subjects under a resting state protocol provided by the ABIDE I Consortium. We found that people with ASD had diminished functional connectivity between the cerebellum and the following cortical regions: (i) right fusiform gyrus, (ii) right postcentral gyrus, (iii) right superior temporal gyrus, (iv) right middle temporal gyrus, and (v) left middle temporal gyrus. All of these regions are involved in many cognitive systems that contribute to commonly affected functions in ASD. For right fusiform gyrus, right superior temporal gyrus, and left middle temporal gyrus, we reproduced the results in an independent cohort composed of 585 subjects of the ABIDE II Consortium. Our results points toward a consistent atypical cortico-cerebellar connectivity in ASD.
| S-EPMC6341229 | biostudies-literature
Project description:Interpersonal distance regulation is an essential element of social communication. Its impairment in autism spectrum disorder (ASD) is widely acknowledged among practitioners, but only a handful of studies reported empirical research in real-life settings, focusing mainly on children. Interpersonal distance in adults with ASD and related autonomic functions received less attention. Here, we measured interpersonal distance along with heart rate variability (HRV) in adults with ASD, and tested the modulatory effects of eye-contact and attribution. Twenty-two adults diagnosed with ASD and 21 matched neurotypical controls participated in our study from October 2019 to February 2020. Our experimental design combined the modified version of the stop distance paradigm with HRV measurement controlling for eye contact between the experimenter and the participant to measure interpersonal distance. Still, we did not detect significant modulatory effect of eye contact and attribution. Our results showed a greater preferred distance in ASD. Moreover, we found lower baseline HRV and reduced HRV reactivity in ASD; however, these autonomic measurements could not predict preferred interpersonal distance. Our study highlights the importance of interpersonal space regulation in ASD: it might be considered that people with ASD need individually variable, presumably greater interpersonal distance. In addition, regardless of the distance they may have reduced autonomic regulatory capacity in social situations. Our results could help shape future experiments with sophisticated designs to grasp the complexity and underlying factors of distance regulation in typical and atypical populations.
| S-EPMC10065277 | biostudies-literature
Project description:BackgroundPrevious research studies have demonstrated abnormalities in the metabolism of mothers of young children with autism.MethodsMetabolic analysis was performed on blood samples from 30 mothers of young children with Autism Spectrum Disorder (ASD-M) and from 29 mothers of young typically-developing children (TD-M). Targeted metabolic analysis focusing on the folate one-carbon metabolism (FOCM) and the transsulfuration pathway (TS) as well as broad metabolic analysis were performed. Statistical analysis of the data involved both univariate and multivariate statistical methods.ResultsUnivariate analysis revealed significant differences in 5 metabolites from the folate one-carbon metabolism and the transsulfuration pathway and differences in an additional 48 metabolites identified by broad metabolic analysis, including lower levels of many carnitine-conjugated molecules. Multivariate analysis with leave-one-out cross-validation allowed classification of samples as belonging to one of the two groups of mothers with 93% sensitivity and 97% specificity with five metabolites. Furthermore, each of these five metabolites correlated with 8-15 other metabolites indicating that there are five clusters of correlated metabolites. In fact, all but 5 of the 50 metabolites with the highest area under the receiver operating characteristic curve were associated with the five identified groups. Many of the abnormalities appear linked to low levels of folate, vitamin B12, and carnitine-conjugated molecules.ConclusionsMothers of children with ASD have many significantly different metabolite levels compared to mothers of typically developing children at 2-5 years after birth.
| S-EPMC7734806 | biostudies-literature
Project description:Autism spectrum disorder (ASD) is associated with disrupted brain networks. Neuroimaging techniques provide noninvasive methods of investigating abnormal connectivity patterns in ASD. In the present study, we compare functional connectivity networks in people with ASD with those in typical controls, using neuroimaging data from the Autism Brain Imaging Data Exchange (ABIDE) project. Specifically, we focus on the characteristics of intrinsic functional connectivity based on data collected by resting-state functional magnetic resonance imaging (rs-fMRI). Our aim was to identify disrupted brain connectivity patterns across all networks, instead of in individual edges, by using advanced statistical methods. Unlike many brain connectome studies, in which networks are prespecified before the edge connectivity in each network is compared between clinical groups, we detected the latent differentially expressed networks automatically. Our network-level analysis identified abnormal connectome networks that (i) included a high proportion of edges that were differentially expressed between people with ASD and typical controls; and (ii) showed highly-organized graph topology. These findings provide new insight into the study of the underlying neuropsychiatric mechanism of ASD.
| S-EPMC5359252 | biostudies-literature
Project description:Changes in the gut microenvironment may influence the pathogenesis of autism spectrum disorders (ASD). Here, we investigated the composition of the gut microbiota and metabolites in children with ASD. Ninety-two children with ASD and 42 age-matched children exhibiting typical development (TD) were enrolled in the two-stage study. In the discovery stage, shotgun metagenomic sequencing and liquid chromatography-mass spectrometry (LC-MS) were performed simultaneously on fecal samples obtained from 43 children in the ASD group and 31 children in the TD group. Systematic bioinformatic analyses were performed to identify gut metabolites associated with altered gut microbiota composition. At the validation stage, differential metabolites were tested using LC-MS with an additional 49 and 11 children in the ASD and TD groups, respectively. Altered glutamate metabolites were found in the ASD group, along with a decline in 2-keto-glutaramic acid and an abundance of microbiota associated with glutamate metabolism. These changes in glutamate metabolism were correlated with lower levels of the highly abundant bacteria Bacteroides vulgatus and higher levels of the potentially harmful Eggerthella lenta and Clostridium botulinum. Lower gut cortisol levels have also been identified in the ASD group and associated with changes in gut microbiota glutamate metabolism. Finally, gut 2-keto-glutaramic acid was validated as a potential biomarker for ASD. The significant changes in the gut microenvironment in children with ASD may provide new insight into the cause of ASD and aid in the search for diagnostic and therapeutic approaches. IMPORTANCE Multiple lines of evidence suggest that the gut microbiota may play an important role in the pathogenesis of ASD, but the specific mechanism is still unclear. Through a comprehensive gut metagenomic and metabolome study of children with ASD, alterations in gut metabolite composition were found in children with ASD, and these alterations were linked to changes in gut microbiota composition. This may give us a deeper understanding of the role of gut microbiota in the pathogenesis of ASD.
| S-EPMC6351726 | biostudies-literature
Project description:Autism spectrum disorders are associated with social and emotional deficits, the aetiology of which are not well understood. A growing consensus is that the autonomic nervous system serves a key role in emotional processes, by providing physiological signals essential to subjective states. We hypothesized that altered autonomic processing is related to the socio-emotional deficits in autism spectrum disorders. Here, we investigated the relationship between non-specific skin conductance response, an objective index of sympathetic neural activity, and brain fluctuations during rest in high-functioning adults with autism spectrum disorder relative to neurotypical controls. Compared with control participants, individuals with autism spectrum disorder showed less skin conductance responses overall. They also showed weaker correlations between skin conductance responses and frontal brain regions, including the anterior cingulate and anterior insular cortices. Additionally, skin conductance responses were found to have less contribution to default mode network connectivity in individuals with autism spectrum disorders relative to controls. These results suggest that autonomic processing is altered in autism spectrum disorders, which may be related to the abnormal socio-emotional behaviours that characterize this condition.
| S-EPMC3891443 | biostudies-other
Project description:Inflammation and the gut-brain axis have been implicated in the pathogenesis of autism spectrum disorders (ASDs). To further understand the relationship between aberrant immune responses and dysbiotic features of the gut microbiome in ASD, we enrolled 45 ASD individuals and 41 healthy control subjects with ages ranging from 2 to 19 years. We found that ASD group subjects have significantly higher plasma levels of IL-2, IL-4, IL-5, IL-6, IL-10, TNF-α, TNF-β, and IFN-γ when compared to healthy controls (FDR-adjusted p < 0.05). The plasma levels of pro-inflammatory cytokines IFN-γ and IL-6 are found to be further associated with several largely pathogenic gut microbiota uniquely detected in subjects with ASD. Furthermore, the ASD gut microbiome is characterized by reduced levels of several beneficial microbiota, including Bacteroides (FDR-adjusted p < 0.01) and Lachnospiraceae (FDR-adjusted p < 0.001). Analysis of Lachnospiraceae family and genus level taxa suggested that relative abundances of such taxa are negatively correlated with pro-inflammatory signaling cytokines IFN-γ and IL-6, particularly in subjects with severe ASD as defined by CARS (p < 0.05). Several largely pathogenic genera are determined to be associated with the pro-inflammatory cytokines IFN-γ and IL-6 (FDR-adjusted p < 0.1). Additionally, IL-4 is significantly negatively correlated with CARS total score (p < 0.05). Based on such results, we propose that the association between the disturbances of specific cytokines and alterations in gut microbiota abundance observed in children and adolescents with ASD provides additional evidence on the induction of aberrant pro-inflammatory mechanisms in ASD and its early diagnosis.
| S-EPMC7902875 | biostudies-literature
Project description:Background: There is accumulating evidence showing that patients with autism spectrum disorder (ASD) have obvious changes in resting-state functional brain activity. So far, there have been no meta-analyses of the resting-state brain activity alterations in patients with ASD. We attempted to explore the resting-state functional activity changes in patients with ASD, possibly providing a new perspective for investigating the pathophysiology of patients with ASD. Methods: We screened relevant studies published before August 2017 in PubMed, Ovid, Web of Science, China National Knowledge Infrastructure (CNKI), and the Wan-fang database. Fifteen resting-state functional neural activity datasets (including 382 patients and 348 healthy controls) were included. Through the use of the effect-size signed differential mapping (ES-SDM) method, we carried out a meta-analysis of resting-state functional activity studies of patients with ASD. Results: Compared with healthy controls, patients with ASD showed hyperactivity in the right supplementary motor area, middle frontal gyrus, inferior frontal gyrus, the left precentral gyrus, and the bilateral cerebellum hemispheric lobule (VIII/IX), and hypoactivity in the right middle temporal gyrus, superior temporal gyrus, and the left precuneus, posterior cingulate cortex, median cingulate cortex, and bilateral cerebellum (crus I). Conclusion: This meta-analysis indicates that patients with ASD have significant and robust resting-state brain activity alterations in the language comprehension network, inferior-posterior cerebellum, default mode network (DMN), and cerebellar crus I. These brain regions may serve as specific regions of interest for further studies of ASD, which will allow us to further clarify the neurobiological mechanisms in patients with ASD.
| S-EPMC6066523 | biostudies-literature