A quasi-paired cohort strategy reveals the impaired detoxifying function of microbes in the gut of autistic children

Abstract

Growing evidence suggests that autism spectrum disorder (ASD) is strongly associated with dysbiosis in the gut microbiome, with the exact mechanisms still unclear. We have proposed a novel analytic strategy—quasi-paired cohort—and applied it to a metagenomic study of the ASD microbiome. By comparing paired samples of ASD and neurotypical subjects, we have identified significant deficiencies in ASD children in detoxifying enzymes and pathways, which show a strong correlation with biomarkers of mitochondrial dysfunction. Diagnostic models based on these detoxifying enzymes accurately distinguished ASD individuals from controls, and the dysfunction score inferred from the model increased with the clinical rating scores of ASD. In summary, our results suggest a previously undiscovered potential role of impaired intestinal microbial detoxification in toxin accumulation and mitochondrial dysfunction, a core component of ASD pathogenesis. These findings pave the way for designing future therapeutic strategies to restore microbial detoxification capabilities for patients with ASD.

Gut lactate-producing bacteria promote CD4 T cell recovery on Anti-retroviral therapy in HIV-infected patients

“…S1 e ). Given the many confounding factors which greatly elevate the inter-individual metagenomic diversity and prevent the identification of causative species or metabolic features from metagenomic data [18] , [19] , we then utilized our newly-developed analytical method – “quasi-paired cohort” which is powerful in control of inter-individual diversity and successful in identifying causative microbiome features of autism [20] ( Fig. 1 a, refer to Methods and Fig.…”

VTwins: Identifying Robust Associations from High-dimensional Data of Limited Samples

“…By direct comparison to the conventional cohort-based analyses, we demonstrate the power and sensitivity of VTwins in identifying robust disease-associated microbes, where statistical power is saliently increased by transforming the original cohort into the paired VTwins cohort. By a similar twin strategy based on the functional pro les of samples, we have successfully identi ed the impairment of detoxi cation in autistic children in a former study 28 . The success of VTwins may rely on the virtual twins it provides as mutual controls for the complexity of all the dimensions, as an adequate number of controls is the premise for causal-relationship mining and is hard to be fully satis ed in the case of hundreds of dimensions.…”

Gene variations in Autism Spectrum Disorder are associated with alternation of gut microbiota, metabolites and cytokines

“…52 Toxin exposure has been epidemiologically demonstrated as one of the main etiological factors of ASD, and deficiencies in toxicant-degradation pathways were reported in ASD. 53 These results implicated the possible genetic factors that were underlying the microbial detoxification deficiency. Besides, a couple of gene variations were associated with the immune system.…”