Dietary Modulation of Gut Microbiota Contributes to Alleviation of Both Genetic and Simple Obesity in Children

Zhang, C; Yin, A; Li, H; Wang, R; Wu, G; Shen, J; Zhang, M; Wang, L; Hou, Y; Ouyang, H; Zhang, Y; Zheng, Y; Wang, J; Lv, X; Wang, Y; Zhang, F; Zeng, B; Li, W; Yan, F; Zhao, Y; Pang, X; Zhang, X; Fu, H; Chen, F; Zhao, N; Hamaker, BR; Bridgewater, LC; Weinkove, D; Clement, K; Dore, J; Holmes, E; Xiao, H; Zhao, G; Yang, S; Bork, P; Nicholson, JK; Wei, H; Tang, H; Zhao, L

Abstract

Gut microbiota has been implicated as a pivotal contributing factor in diet-related obesity; however, its role in development of disease phenotypes in human genetic obesity such as Prader–Willi syndrome (PWS) remains elusive. In this hospitalized intervention trial with PWS (n = 17) and simple obesity (n = 21) children, a diet rich in non-digestible carbohydrates induced significant weight loss and concomitant structural changes of the gut microbiota together with reduction of serum antigen load and alleviation of inflammation. Co-abundance network analysis of 161 prevalent bacterial draft genomes assembled directly from metagenomic datasets showed relative increase of functional genome groups for acetate production from carbohydrates fermentation. NMR-based metabolomic profiling of urine showed diet-induced overall changes of host metabotypes and identified significantly reduced trimethylamine N-oxide and indoxyl sulfate, host-bacteria co-metabolites known to induce metabolic deteriorations. Specific bacterial genomes that were correlated with urine levels of these detrimental co-metabolites were found to encode enzyme genes for production of their precursors by fermentation of choline or tryptophan in the gut. When transplanted into germ-free mice, the pre-intervention gut microbiota induced higher inflammation and larger adipocytes compared with the post-intervention microbiota from the same volunteer. Our multi-omics-based systems analysis indicates a significant etiological contribution of dysbiotic gut microbiota to both genetic and simple obesity in children, implicating a potentially effective target for alleviation.

Citation

Zhang, C., Yin, A., Li, H., Wang, R., Wu, G., Shen, J., …Zhao, L. (2015). Dietary Modulation of Gut Microbiota Contributes to Alleviation of Both Genetic and Simple Obesity in Children. EBioMedicine, 2(8), 968-984. https://doi.org/10.1016/j.ebiom.2015.07.007

• Journal Article Type: Article
• Acceptance Date: Sep 11, 2015
• Publication Date: Aug 1, 2015
• Deposit Date: Sep 11, 2015
• Publicly Available Date: Oct 29, 2015
• Journal: EBioMedicine
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 2
• Issue: 8
• Pages: 968-984
• DOI: https://doi.org/10.1016/j.ebiom.2015.07.007
• Keywords: Prader–Willi syndrome, Obesity, Gut microbiota, Metagenomics, Metabolomics, Genome interaction network
• Public URL: https://durham-repository.worktribe.com/output/1423027