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 of gastrointestinal and behavioral symptoms. We also reported modulation of the gut microbiome toward 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, IMP, iminodiacetate, methylsuccinate, galactonate, valylglycine, sarcosine, and leucylglycine) were significantly lower in the ASD group at baseline, while caprylate and heptanoate were significantly higher in the 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 hypotheses, no metabolite was significantly different at baseline. Although not statistically significant, p-cresol sulfate was relatively higher in the ASD group at baseline, and after MTT, the levels decreased and were similar to levels in typically developing (TD) controls. p-Cresol sulfate levels were inversely correlated with Desulfovibrio, suggesting a potential 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.

中文翻译：

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自闭症谱系障碍儿童的不同粪便和血浆代谢物及其在微生物群转移治疗后的调节

越来越多的证据加强了肠道菌群失调与自闭症之间的联系。粪便微生物群移植（FMT）是一种很有前景的修复肠道菌群失调的疗法。我们之前对自闭症谱系障碍 (ASD) 儿童进行了称为微生物群转移疗法 (MTT) 的强化 FMT，并观察到胃肠道和行为症状的显着改善。我们还报告了肠道微生物群向健康微生物群的调节。在这项研究中，我们报告了参与 MTT 试验的儿童血浆和粪便样本的综合代谢物谱。通过检测到 619 种血浆代谢物，我们发现自闭症组在基线时具有独特的代谢特征。八种代谢物（烟酰胺核糖苷、IMP、亚氨基二乙酸酯、琥珀酸甲酯、半乳糖酸、缬氨酰甘氨酸、肌氨酸、和亮氨酰甘氨酸）在基线时在 ASD 组中显着较低，而在 ASD 组中辛酸和庚酸显着较高。MTT 推动了各种代谢特征的血浆谱的全球变化，包括烟酸盐/烟酰胺和嘌呤代谢。相比之下，对于检测到的 669 种粪便代谢物，在校正多个假设时，基线时没有代谢物有显着差异。虽然没有统计学意义，没有代谢物在基线时有显着差异。虽然没有统计学意义，没有代谢物在基线时有显着差异。虽然没有统计学意义，基线时 ASD 组的对甲酚硫酸盐相对较高，在 MTT 后，水平下降，与典型发育 (TD) 对照组的水平相似。p甲酚硫酸盐水平呈负相关与脱硫，提示的潜在作用脱硫上p甲酚硫酸盐调制。有必要在更大的 ASD 队列中进一步研究 MTT 之前和之后的代谢物，以及其他疗法的临床试验，以解决 MTT 无法纠正的代谢变化。