Multikingdom and functional gut microbiota markers for autism spectrum disorder, 2024, Su et al

Multikingdom and functional gut microbiota markers for autism spectrum disorder

Published: 8 July 2024

Qi Su, Oscar W. H. Wong, Wenqi Lu, Yating Wan, Lin Zhang, Wenye Xu, Moses K. T. Li, Chengyu Liu, Chun Pan Cheung, Jessica Y. L. Ching, Pui Kuan Cheong, Ting Fan Leung, Sandra Chan, Patrick Leung, Francis K. L. Chan, Siew C. Ng

Abstract
Associations between the gut microbiome and autism spectrum disorder (ASD) have been investigated although most studies have focused on the bacterial component of the microbiome. Whether gut archaea, fungi and viruses, or function of the gut microbiome, is altered in ASD is unclear. Here we performed metagenomic sequencing on faecal samples from 1,627 children (aged 1–13 years, 24.4% female) with or without ASD, with extensive phenotype data. Integrated analyses revealed that 14 archaea, 51 bacteria, 7 fungi, 18 viruses, 27 microbial genes and 12 metabolic pathways were altered in children with ASD. Machine learning using single-kingdom panels showed area under the curve (AUC) of 0.68 to 0.87 in differentiating children with ASD from those that are neurotypical. A panel of 31 multikingdom and functional markers showed a superior diagnostic accuracy with an AUC of 0.91, with comparable performance for males and females. Accuracy of the model was predominantly driven by the biosynthesis pathways of ubiquinol-7 or thiamine diphosphate, which were less abundant in children with ASD. Collectively, our findings highlight the potential application of multikingdom and functional gut microbiota markers as non-invasive diagnostic tools in ASD.

Competing interests
F.K.L.C. is a Board Member of CUHK Medical Centre. He is a co-founder, non-executive Board Chairman, honorary Chief Medical Officer and shareholder of GenieBiome Ltd. He receives patent royalties through his affiliated institutions. He has received fees as an advisor and honoraria as a speaker for Eisai Co. Ltd., AstraZeneca, Pfizer Inc., Takeda Pharmaceutical Co., and Takeda (China) Holdings Co. Ltd. S.C.N. has served as an advisory board member for Pfizer, Ferring, Janssen, and Abbvie and received honoraria as a speaker for Ferring, Tillotts, Menarini, Janssen, Abbvie, and Takeda. She has received research grants through her affiliated institutions from Olympus, Ferring, and Abbvie, and is a scientific co-founder and shareholder of GenieBiome Ltd. She also receives patent royalties through her affiliated institutions. Q.S., L.Z., Y.W., F.K.L.C. and S.C.N. are named inventors of patent applications (no. 63/533,871, US, 2023) held by the CUHK and MagIC that cover the therapeutic and diagnostic use of microbiome. The remaining authors declare no competing interests.


Link (Nature Microbiology) [Paywall]