ArticleNature microbiology2022
Gut microbial β-glucuronidases regulate host luminal proteases and are depleted in irritable bowel syndrome.
Article in Nature microbiology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
62 citing papers in PubMed, 1 synthesis or guideline pooled it, 85 citations in OpenAlex.
- Serological and faecal markers of irritable bowel syndrome: a systematic review and meta-analysis.EBioMedicine · 2026Pooled it
- Towards optimizing the host response to biotics: a report of an International Scientific Association for Probiotics and Prebiotics working group.Gut microbes · 2026Article
- Irritable bowel syndrome.Nature reviews. Disease primers · 2026Review
- Exploring the Possible Role of Endometriosis-Associated Dysbiosis in Endometrial Carcinogenesis.Medicina (Kaunas, Lithuania) · 2026Review
- Association Between Gut Microbiota Dysbiosis and Bilirubin Metabolism Dysregulation in Children with Heart Failure.Journal of cardiovascular translational research · 2026Article
- Chitosan-Unconjugated Bilirubin Microspheres Alleviate Dysbiosis, Immune Dysregulation, and Intestinal Barrier Damage in Ulcerative Colitis.Biomolecules · 2026Article
- Article
- Gut Microbiota and Extraintestinal Cancers: Mechanistic Insights and Microbiome-Targeted Interventions.JGH open : an open access journal of gastroenterology and hepatology · 2026Review
- Gut microbiota modulates synaptic plasticity, connectivity, and dopamine transmission in the VTA-mPFC pathway in bipolar depression.Molecular psychiatry · 2026Article
- The Role of Lactobacillus Strain Probiotics in Breast Cancer: Strain-Specific Mechanisms and Therapeutic Potential Beyond Probiotics.Probiotics and antimicrobial proteins · 2026Review
- Diet, the Gut Microbiome, and Estrogen Physiology: A Review in Menopausal Health and Interventions.Nutrients · 2026Review
- β-Glucuronidase at the Microbiota-Host Interface: Dual Regulatory Roles and Precision Modulation by Natural Products.Molecules (Basel, Switzerland) · 2026Review
- Proteases and Abdominal Pain-Old Dog, New (Microbial) Tricks.Cellular and molecular gastroenterology and hepatology · 2026Review
- Proteases in intestinal health and disease.Nature reviews. Gastroenterology & hepatology · 2026Review
- The role of theFrontiers in microbiology · 2026Review
- Multi-omics mendelian randomization integrating GWAS and eQTL data revealed potential drug target for irritable bowel syndrome.Frontiers in genetics · 2026Article
- Research on the combination ofBioscience of microbiota, food and health · 2026Article
- Protease profiling in fecal samples: a novel non-invasive diagnostic tool for gastrointestinal disorders.Scientific reports · 2025Article
- Gut microbiota-mediated modulation of host amino acid availability and metabolism.Gut microbes · 2025Review
- Interaction between the breast tumor microenvironment and gut microbiome.Gut microbes · 2025Review
2 more citing papers are in PubMed but not listed here.
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Authors and funding
23 authors at 6 institutions in 2 countries.
Funding
Abstract
Intestinal proteases mediate digestion and immune signalling, while increased gut proteolytic activity disrupts the intestinal barrier and generates visceral hypersensitivity, which is common in irritable bowel syndrome (IBS). However, the mechanisms controlling protease function are unclear. Here we show that members of the gut microbiota suppress intestinal proteolytic activity through production of unconjugated bilirubin. This occurs via microbial β-glucuronidase-mediated conversion of bilirubin conjugates. Metagenomic analysis of faecal samples from patients with post-infection IBS (n = 52) revealed an altered gut microbiota composition, in particular a reduction in Alistipes taxa, and high gut proteolytic activity driven by specific host serine proteases compared with controls. Germ-free mice showed 10-fold higher proteolytic activity compared with conventional mice. Colonization with microbiota samples from high proteolytic activity IBS patients failed to suppress proteolytic activity in germ-free mice, but suppression of proteolytic activity was achieved with colonization using microbiota from healthy donors. High proteolytic activity mice had higher intestinal permeability, a higher relative abundance of Bacteroides and a reduction in Alistipes taxa compared with low proteolytic activity mice. High proteolytic activity IBS patients had lower fecal β-glucuronidase activity and end-products of bilirubin deconjugation. Mice treated with unconjugated bilirubin and β-glucuronidase-overexpressing E. coli significantly reduced proteolytic activity, while inhibitors of microbial β-glucuronidases increased proteolytic activity. Together, these data define a disease-relevant mechanism of host-microbial interaction that maintains protease homoeostasis in the gut.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.