ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2015
Human Clostridium difficile infection: inhibition of NHE3 and microbiota profile.
Article in American journal of physiology. Gastrointestinal and liver physiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.
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Who cites it
76 citing papers in PubMed, 94 citations in OpenAlex.
- Ecological and dietary strategies to constrain Clostridioides difficile.Cell host & microbe · 2026Review
- New developments and applications of human organoids.Nature reviews. Molecular cell biology · 2026Review
- Dual Fluorescent Labeling for Bacterial Aggregation Assays.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Robust high-sensitivity real-time impedance analysis for neutralization drug screening and toxicity kinetics ofFrontiers in microbiology · 2026Article
- Applications and research trends in organoid based infectious disease models.Scientific reports · 2025Review
- Modeling cancer-microbiome interactions in vitro: A guide to co-culture platforms.International journal of cancer · 2025Review
- From Bioreactors to Organoids: Tools for Culturing and Understanding Microbiota.Indian journal of microbiology · 2025Review
- The Role of Intestinal Microbiota and Dietary Fibre in the Regulation of Blood Pressure Through the Interaction with Sodium: A Narrative Review.Microorganisms · 2025Review
- The Use of Gut Organoids: To Study the Physiology and Disease of the Gut Microbiota.Journal of cellular and molecular medicine · 2025Review
- Diet-Microbiota-Host Interactions in Regulation of Cardiometabolic Homeostasis: Emerging Mechanisms and Therapeutic Potential.Microbiota and host · 2025Article
- Both pathogen and host dynamically adapt pH responses along the intestinal tract during enteric bacterial infection.PLoS biology · 2024Article
- Advancements in understanding bacterial enteritis pathogenesis through organoids.Molecular biology reports · 2024Review
- New functions and roles of the NaPflugers Archiv : European journal of physiology · 2024Review
- Salt and Gut Microbiota in Heart Failure.Current hypertension reports · 2023Review
- Stem cell-derived intestinal organoids: a novel modality for IBD.Cell death discovery · 2023Review
- Intestinal organoids as advanced modeling platforms to study the role of host-microbiome interaction in homeostasis and disease.BMB reports · 2023Review
- Assays with Patient-Derived Organoids to Evaluate the Impact of Microbial Infection on Base Excision Repair (BER) Enzymes.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Article
- Receptor Guanylyl Cyclase C and Cyclic GMP in Health and Disease: Perspectives and Therapeutic Opportunities.Frontiers in endocrinology · 2022Review
- The Role of Plasma Membrane Sodium/Hydrogen Exchangers in Gastrointestinal Functions: Proliferation and Differentiation, Fluid/Electrolyte Transport and Barrier Integrity.Frontiers in physiology · 2022Review
16 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Clostridium difficile infection (CDI) is principally responsible for hospital acquired, antibiotic-induced diarrhea and colitis and represents a significant financial burden on our healthcare system. Little is known about C. difficile proliferation requirements, and a better understanding of these parameters is critical for development of new therapeutic targets. In cell lines, C. difficile toxin B has been shown to inhibit Na(+)/H(+) exchanger 3 (NHE3) and loss of NHE3 in mice results in an altered intestinal environment coupled with a transformed gut microbiota composition. However, this has yet to be established in vivo in humans. We hypothesize that C. difficile toxin inhibits NHE3, resulting in alteration of the intestinal environment and gut microbiota. Our results demonstrate that CDI patient biopsy specimens have decreased NHE3 expression and CDI stool has elevated Na(+) and is more alkaline compared with stool from healthy individuals. CDI stool microbiota have increased Bacteroidetes and Proteobacteria and decreased Firmicutes phyla compared with healthy subjects. In vitro, C. difficile grows optimally in the presence of elevated Na(+) and alkaline pH, conditions that correlate to changes observed in CDI patients. To confirm that inhibition of NHE3 was specific to C. difficile, human intestinal organoids (HIOs) were injected with C. difficile or healthy and CDI stool supernatant. Injection of C. difficile and CDI stool decreased NHE3 mRNA and protein expression compared with healthy stool and control HIOs. Together these data demonstrate that C. difficile inhibits NHE3 in vivo, which creates an altered environment favored by C. difficile.
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Registered trials
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.