ArticleAmerican journal of physiology. Lung cellular and molecular physiology2021
Lung immune tone via gut-lung axis: gut-derived LPS and short-chain fatty acids' immunometabolic regulation of lung IL-1β, FFAR2, and FFAR3 expression.
Article in American journal of physiology. Lung cellular and molecular physiology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 101 papers, 2 of them syntheses that pooled it.
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Who cites it
101 citing papers in PubMed, 2 syntheses or guidelines pooled it, 138 citations in OpenAlex.
- Frailty in COPD: Clinical Impact, Diagnosis, Biomarkers, and Management Strategies.International journal of chronic obstructive pulmonary disease · 2025Pooled it
- Therapeutic potential of short-chain fatty acids for acute lung injury: a systematic review and meta-analysis of preclinical animal studies.Frontiers in nutrition · 2024Pooled it
- Effect of probiotics derivatives (postbiotics and metabiotics) on glycemic control in individuals with type 2 diabetes: a randomized clinical trial (DELI_Diab study).Frontiers in endocrinology · 2026Trial
- Gut microbiome-derived propionate reprograms alveolar macrophages metabolically and regulates lung injury responses in mice.Gut microbes · 2026Article
- NEC-Associated Bronchopulmonary Dysplasia and the Gut-Lung Axis in Preterm Infants.American journal of perinatology · 2026Review
- Multi-Omics Profiling Identifies Immune-Metabolic Signatures and Gut Microbial Biomarkers in a Murine Model ofBiology · 2026Article
- Hepatic control of immunometabolism: implications for the pathogenesis, diagnosis and treatment of rheumatic diseases.Nature reviews. Rheumatology · 2026Review
- The Gut-Lung Microbiome Axis in Alveolar Stem Cell Regeneration and Lung Repair.Microorganisms · 2026Review
- The gut-lung axis in ARDS: beyond microbial translocation.Respiratory research · 2026Review
- Upper and Lower Respiratory Tract Compartmentalization in Pediatric Stem Cell Transplantation.American journal of respiratory cell and molecular biology · 2026Article
- Plasma short-chain fatty acids are associated with COPD and COPD phenotypes.BMC pulmonary medicine · 2026Observational
- Clozapine disrupts the gut-lung microbiota axis, linking gastrointestinal hypomotility to increased respiratory vulnerability.Translational psychiatry · 2026Article
- Butyrate remodels the immune-epigenetic-gut-lung axis: Emerging mechanisms and therapeutic perspectives in asthma.Seminars in immunopathology · 2026Review
- The Dynamic Gut Microbiota: Monitoring Alterations During Lung Cancer Progression for Diagnosis and Precision Medicine.International journal of molecular sciences · 2026Review
- Harnessing the Gut Microbiota to Improve Cancer Immunotherapy: Focus on Lung Cancer.Immune network · 2026Review
- Gut microbiota and metabolites in acute lung injury: mechanisms and therapeutic perspectives.Respiratory research · 2026Review
- Gut microbiota in acute lung injury/acute respiratory distress syndrome: mechanistic insights and therapeutic opportunities via the gut-lung axis.Frontiers in cellular and infection microbiology · 2026Review
- Pyroptosis endotypes and nonlinear biomarker-mortality relationships in older adults with community-acquired pneumonia: the amplifying role of malnutrition.Frontiers in immunology · 2026Article
- The role of intestinal microbiota in the pathogenesis of childhood asthma.Frontiers in immunology · 2026Review
- Preventing ventilator-associated pneumonia via the gut-lung axis: the Shenling Baizhu San hypothesis.Frontiers in medicine · 2026Article
41 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
Microbial metabolites produced by the gut microbiome, e.g. short-chain fatty acids (SCFA), have been found to influence lung physiology and injury responses. However, how lung immune activity is regulated by SCFA is unknown. We examined fresh human lung tissue and observed the presence of SCFA with interindividual variability. In vitro, SCFA were capable of modifying the metabolic programming in LPS-exposed alveolar macrophages (AM). We hypothesized that lung immune tone could be defined by baseline detection of lung intracellular IL-1β. Therefore, we interrogated naïve mouse lungs with intact gut microbiota for IL-1β mRNA expression and localized its presence within alveolar spaces, specifically within AM subsets. We established that metabolically active gut microbiota, which produce SCFA, can transmit LPS and SCFA to the lung and thereby could create primed lung immunometabolic tone. To understand how murine lung cells sensed and upregulated IL-1β in response to gut microbiome-derived factors, we determined that, in vitro, AM and alveolar type II (AT2) cells expressed SCFA receptors, free fatty acid receptor 2 (FFAR2), free fatty acid receptor 3 (FFAR3), and IL-1β but with distinct expression patterns and different responses to LPS. Finally, we observed that IL-1β, FFAR2, and FFAR3 were expressed in isolated human AM and AT2 cells ex vivo, but in fresh human lung sections in situ, only AM expressed IL-1β at rest and after LPS challenge. Together, this translational study using mouse and human lung tissue and cells point to an important role for the gut microbiome and their SCFA in establishing and regulating lung immune tone.
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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.