Microbial genetic and transcriptional contributions to oxalate degradation by the gut microbiota in health and disease

eLife

Martin J Blaser¹  Allyson Byrd²  John R Asplin³  Jiyuan Hu⁴  Melody Ho⁴  Huilin Li⁴  Thomas W Battaglia⁴  Kelly V Ruggles⁴  P'ng Loke⁴  Aristotelis Tsirigos⁴  Lama Nazzal⁴  Joseph C Devlin⁵  Angelina Volkova⁵  Menghan Liu⁵ 

[1] Center for Advanced Biotechnology and Medicine, Rutgers University, New York, United States;Department of Cancer Immunology, Genentech Inc, South San Francisco, United States;Litholink Corporation, Laboratory Corporation of America Holdings, Chicago, United States;NYU Langone Health, New York, United States;NYU Langone Health, New York, United States;Vilcek Institute of Graduate Biomedical Sciences, New York, United States;

关键词: microbiota;    oxalate metabolism;    metatranscriptome;    metagenome;    IBD;    gene expressions;    Human;    Mouse;   

DOI  :  10.7554/eLife.63642

来源: eLife Sciences Publications, Ltd

【 摘 要 】

Over-accumulation of oxalate in humans may lead to nephrolithiasis and nephrocalcinosis. Humans lack endogenous oxalate degradation pathways (ODP), but intestinal microbes can degrade oxalate using multiple ODPs and protect against its absorption. The exact oxalate-degrading taxa in the human microbiota and their ODP have not been described. We leverage multi-omics data (>3000 samples from >1000 subjects) to show that the human microbiota primarily uses the type II ODP, rather than type I. Furthermore, among the diverse ODP-encoding microbes, an oxalate autotroph, Oxalobacter formigenes, dominates this function transcriptionally. Patients with inflammatory bowel disease (IBD) frequently suffer from disrupted oxalate homeostasis and calcium oxalate nephrolithiasis. We show that the enteric oxalate level is elevated in IBD patients, with highest levels in Crohn’s disease (CD) patients with both ileal and colonic involvement consistent with known nephrolithiasis risk. We show that the microbiota ODP expression is reduced in IBD patients, which may contribute to the disrupted oxalate homeostasis. The specific changes in ODP expression by several important taxa suggest that they play distinct roles in IBD-induced nephrolithiasis risk. Lastly, we colonize mice that are maintained in the gnotobiotic facility with O. formigenes, using either a laboratory isolate or an isolate we cultured from human stools, and observed a significant reduction in host fecal and urine oxalate levels, supporting our in silico prediction of the importance of the microbiome, particularly O. formigenes in host oxalate homeostasis.

【 授权许可】

CC BY