Accumulating evidence has strengthened a link between dysbiotic gut microbiota and autism. Fecal microbiota transplant (FMT) is a promising therapy to repair dysbiotic gut microbiota. We previously performed intensive FMT called microbiota transfer therapy (MTT) for children with autism spectrum disorders (ASD) and observed a substantial improvement on gastrointestinal and behavioral symptoms. We also reported modulation of gut microbiome towards a healthy one. In this study, we report comprehensive metabolite profiles from plasma and fecal samples of the children who participated in the MTT trial. With 619 plasma metabolites detected, we found that the autism group had distinctive metabolic profiles at baseline. Eight metabolites (nicotinamide riboside, inosine 5’-monophosphate, iminodiacetate, methylsuccinate, galactonate, valylglycine, sarcosine and leucylglycine) were significantly lower in ASD group at baseline, while caprylate and heptanoate were significantly higher in ASD group. MTT drove global shifts in plasma profiles across various metabolic features including nicotinate/nicotinamide- and purine metabolism. In contrast, for 669 fecal metabolites detected, when correcting for multiple hypothesis, no metabolite was significantly different at baseline. Although not statistically significant, p-cresol sulfate was relatively higher in ASD group at baseline, and after MTT the levels decreased and were similar to levels in typically developing controls. p-cresol sulfate levels were inversely correlated with Desulfovibrio, suggesting a potentially role of Desulfovibrio on p-cresol sulfate modulation. Further studies of metabolites in a larger ASD cohort, before and after MTT, are warranted, as well as clinical trials of other therapies to address the metabolic changes which MTT was not able to correct.
mSphere 5:e00314-20 (2020) Editor's Pick