Microbial genetic and transcriptional contributions to oxalate degradation by the gut microbiota in health and disease
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 microb...
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2021-03-01
|
| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/63642 |
| _version_ | 1811252940175835136 |
|---|---|
| author | Menghan Liu Joseph C Devlin Jiyuan Hu Angelina Volkova Thomas W Battaglia Melody Ho John R Asplin Allyson Byrd P'ng Loke Huilin Li Kelly V Ruggles Aristotelis Tsirigos Martin J Blaser Lama Nazzal |
| author_facet | Menghan Liu Joseph C Devlin Jiyuan Hu Angelina Volkova Thomas W Battaglia Melody Ho John R Asplin Allyson Byrd P'ng Loke Huilin Li Kelly V Ruggles Aristotelis Tsirigos Martin J Blaser Lama Nazzal |
| author_sort | Menghan Liu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T16:42:23Z |
| format | Article |
| id | doaj.art-799afee30bd04a639dcdd3479eee4bfb |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T16:42:23Z |
| publishDate | 2021-03-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-799afee30bd04a639dcdd3479eee4bfb2022-12-22T03:24:43ZengeLife Sciences Publications LtdeLife2050-084X2021-03-011010.7554/eLife.63642Microbial genetic and transcriptional contributions to oxalate degradation by the gut microbiota in health and diseaseMenghan Liu0https://orcid.org/0000-0002-9390-8194Joseph C Devlin1Jiyuan Hu2Angelina Volkova3Thomas W Battaglia4Melody Ho5John R Asplin6Allyson Byrd7P'ng Loke8https://orcid.org/0000-0002-6211-3292Huilin Li9Kelly V Ruggles10https://orcid.org/0000-0002-0152-0863Aristotelis Tsirigos11Martin J Blaser12https://orcid.org/0000-0003-2447-2443Lama Nazzal13https://orcid.org/0000-0003-0106-5060NYU Langone Health, New York, United States; Vilcek Institute of Graduate Biomedical Sciences, New York, United StatesNYU Langone Health, New York, United States; Vilcek Institute of Graduate Biomedical Sciences, New York, United StatesNYU Langone Health, New York, United StatesNYU Langone Health, New York, United States; Vilcek Institute of Graduate Biomedical Sciences, New York, United StatesNYU Langone Health, New York, United StatesNYU Langone Health, New York, United StatesLitholink Corporation, Laboratory Corporation of America Holdings, Chicago, United StatesDepartment of Cancer Immunology, Genentech Inc, South San Francisco, United StatesNYU Langone Health, New York, United StatesNYU Langone Health, New York, United StatesNYU Langone Health, New York, United StatesNYU Langone Health, New York, United StatesCenter for Advanced Biotechnology and Medicine, Rutgers University, New York, United StatesNYU Langone Health, New York, United StatesOver-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.https://elifesciences.org/articles/63642microbiotaoxalate metabolismmetatranscriptomemetagenomeIBDgene expressions |
| spellingShingle | Menghan Liu Joseph C Devlin Jiyuan Hu Angelina Volkova Thomas W Battaglia Melody Ho John R Asplin Allyson Byrd P'ng Loke Huilin Li Kelly V Ruggles Aristotelis Tsirigos Martin J Blaser Lama Nazzal Microbial genetic and transcriptional contributions to oxalate degradation by the gut microbiota in health and disease eLife microbiota oxalate metabolism metatranscriptome metagenome IBD gene expressions |
| title | Microbial genetic and transcriptional contributions to oxalate degradation by the gut microbiota in health and disease |
| title_full | Microbial genetic and transcriptional contributions to oxalate degradation by the gut microbiota in health and disease |
| title_fullStr | Microbial genetic and transcriptional contributions to oxalate degradation by the gut microbiota in health and disease |
| title_full_unstemmed | Microbial genetic and transcriptional contributions to oxalate degradation by the gut microbiota in health and disease |
| title_short | Microbial genetic and transcriptional contributions to oxalate degradation by the gut microbiota in health and disease |
| title_sort | microbial genetic and transcriptional contributions to oxalate degradation by the gut microbiota in health and disease |
| topic | microbiota oxalate metabolism metatranscriptome metagenome IBD gene expressions |
| url | https://elifesciences.org/articles/63642 |
| work_keys_str_mv | AT menghanliu microbialgeneticandtranscriptionalcontributionstooxalatedegradationbythegutmicrobiotainhealthanddisease AT josephcdevlin microbialgeneticandtranscriptionalcontributionstooxalatedegradationbythegutmicrobiotainhealthanddisease AT jiyuanhu microbialgeneticandtranscriptionalcontributionstooxalatedegradationbythegutmicrobiotainhealthanddisease AT angelinavolkova microbialgeneticandtranscriptionalcontributionstooxalatedegradationbythegutmicrobiotainhealthanddisease AT thomaswbattaglia microbialgeneticandtranscriptionalcontributionstooxalatedegradationbythegutmicrobiotainhealthanddisease AT melodyho microbialgeneticandtranscriptionalcontributionstooxalatedegradationbythegutmicrobiotainhealthanddisease AT johnrasplin microbialgeneticandtranscriptionalcontributionstooxalatedegradationbythegutmicrobiotainhealthanddisease AT allysonbyrd microbialgeneticandtranscriptionalcontributionstooxalatedegradationbythegutmicrobiotainhealthanddisease AT pngloke microbialgeneticandtranscriptionalcontributionstooxalatedegradationbythegutmicrobiotainhealthanddisease AT huilinli microbialgeneticandtranscriptionalcontributionstooxalatedegradationbythegutmicrobiotainhealthanddisease AT kellyvruggles microbialgeneticandtranscriptionalcontributionstooxalatedegradationbythegutmicrobiotainhealthanddisease AT aristotelistsirigos microbialgeneticandtranscriptionalcontributionstooxalatedegradationbythegutmicrobiotainhealthanddisease AT martinjblaser microbialgeneticandtranscriptionalcontributionstooxalatedegradationbythegutmicrobiotainhealthanddisease AT lamanazzal microbialgeneticandtranscriptionalcontributionstooxalatedegradationbythegutmicrobiotainhealthanddisease |