Role of the gut-lung axis in bronchopulmonary dysplasia: Physiological basis, pathogenesis and immunological modulation (Review)

Bronchopulmonary dysplasia (BPD) is a severe respiratory condition that affects preterm infants, which is frequently associated with a poor long-term prognosis. The gut-lung axis is a bidirectional communication pathway mediated by microbial communities and shared immune mechanisms that has emerged as a important area of research. It has been indicated that gut microbiota can influence the progression of various pulmonary diseases, where the gut-lung axis can affect the progression of BPD through various mechanisms, such as bacterial translocation, microbial metabolite exchange, inflammatory cytokine spillover and immune cell migration. Although the relationship between the gut-lung axis and BPD remains under exploration, understanding this interaction may identify early warning markers and novel therapeutic strategies for BPD. The present review summarizes the influence of the gut-lung axis on BPD, focusing on the bidirectional communication and gut microenvironmental changes during BPD and the possible immunoregulatory mechanisms involved. By elucidating these associations, the present review aims to provide novel insights into the prevention and treatment of BPD.

• Publication year

  2025

• Venue

  Molecular Medicine Reports

• Publication date

  2025-09-09

• Fields of study

  Biology, Medicine, Environmental Science

• Identifiers
  DOI 10.3892/mmr.2025.13678PMID 40937590PMCID 12447068
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Characterization of gut microbiota in very low birth weight infants with versus without bronchopulmonary dysplasia

  2025cited by this paper
• The fungal microbiota modulate neonatal oxygen-induced lung injury

  2025cited by this paper
• Feedback delivery of BMP 7 on the pathological oxidative stress via smart hyaluronic acid hydrogel potentiated the repairing of the gut epithelial integrity.

  2024cited by this paper
• Comparative efficacy of probiotic mixture Bifidobacterium longum KABP042 plus Pediococcus pentosaceus KABP041 vs. Limosilactobacillus reuteri DSM17938 in the management of infant colic: a randomized clinical trial

  2024cited by this paper
• The emerging roles of microbiome and short-chain fatty acids in the pathogenesis of bronchopulmonary dysplasia

  2024cited by this paper
• Gut microecology: effective targets for natural products to modulate uric acid metabolism

  2024cited by this paper
• Antibiotics and beyond: Unraveling the dynamics of bronchopulmonary dysplasia in very preterm infants

  2024cited by this paper
• The role of gut-lung axis in COPD: Pathogenesis, immune response, and prospective treatment

  2024cited by this paper
• The Role of Prebiotics in Modulating Gut Microbiota: Implications for Human Health

  2024cited by this paper
• Application of Microbiome-Based Therapies in Chronic Respiratory Diseases

  2024cited by this paper
• Long-term outcomes of infants with severe BPD.

  2024cited by this paper
• Lactobacillus plantarum L168 improves hyperoxia-induced pulmonary inflammation and hypoalveolarization in a rat model of bronchopulmonary dysplasia

  2024influential reference
• Intestinal microbiota programming of alveolar macrophages influences severity of respiratory viral infection.

  2024cited by this paper
• Preterm Infants’ Airway Microbiome: A Scoping Review of the Current Evidence

  2024cited by this paper
• Synergistic effects of achieving perinatal interventions on bronchopulmonary dysplasia in preterm infants

  2024cited by this paper
• Extraembryonic gut endoderm cells undergo programmed cell death during development

  2024cited by this paper
• The cross-talk between the metabolome and microbiome in a double-hit neonatal rat model of bronchopulmonary dysplasia.

  2024cited by this paper
• Type 2 innate lymphoid cell-derived amphiregulin regulates type II alveolar epithelial cell transdifferentiation in a mouse model of bronchopulmonary dysplasia.

  2023cited by this paper
• Association of Ureaplasma infection pattern and azithromycin treatment effect with bronchopulmonary dysplasia in Ureaplasma positive infants: a cohort study

  2023cited by this paper
• Bronchopulmonary Dysplasia: Pathogenesis and Pathophysiology

  2023influential reference
• ILC2 regulates hyperoxia-induced lung injury via an enhanced Th17 cell response in the BPD mouse model

  2023cited by this paper
• Home-site advantage for host species–specific gut microbiota

  2023cited by this paper
• The propionate-GPR41 axis in infancy protects from subsequent bronchial asthma onset

  2023cited by this paper
• Layered immune system development in mice and humans

  2023cited by this paper
• Programmed and environmental determinants driving neonatal mucosal immune development.

  2023cited by this paper
• Dynamic Changes of NCR− Type 3 Innate Lymphoid Cells and Their Role in Mice with Bronchopulmonary Dysplasia

  2022cited by this paper
• The Microbiota-Gut Axis in Premature Infants: Physio-Pathological Implications

  2022cited by this paper
• Epigenetic regulation by gut microbiota

  2022cited by this paper
• Airway-delivered short-chain fatty acid acetate boosts antiviral immunity during rhinovirus infection.

  2022cited by this paper
• Mesenchymal-epithelial interaction regulates gastrointestinal tract development in mouse embryos.

  2022cited by this paper
• Epigenetic reactivation of transcriptional programs orchestrating fetal lung development in human pulmonary hypertension

  2022cited by this paper
• Microbial and metabolic profiles of bronchopulmonary dysplasia and therapeutic effects of potential probiotics Limosilactobacillus reuteri and Bifidobacterium bifidum

  2022cited by this paper
• The Change of Cytokines and Gut Microbiome in Preterm Infants for Bronchopulmonary Dysplasia

  2022cited by this paper
• Association between probiotics and bronchopulmonary dysplasia in preterm infants

  2021cited by this paper
• Necrotizing enterocolitis and the gut-lung axis.

  2021cited by this paper
• Microbiota-derived acetate activates intestinal innate immunity via the Tip60 histone acetyltransferase complex.

  2021cited by this paper
• Wnt signaling in lung development, regeneration, and disease progression

  2021cited by this paper
• Recent Advances in Bronchopulmonary Dysplasia

  2021cited by this paper
• Lactobacillus reuteri Colonisation of Extremely Preterm Infants in a Randomised Placebo-Controlled Trial

  2021cited by this paper
• Maternal Microbiota, Early Life Colonization and Breast Milk Drive Immune Development in the Newborn

  2021cited by this paper
• Respiratory Tract Microecology and Bronchopulmonary Dysplasia in Preterm Infants

  2021cited by this paper
• Diagnosis and management of bronchopulmonary dysplasia

  2021cited by this paper
• The administration of a pre-digested fat-enriched formula prevents necrotising enterocolitis-induced lung injury in mice

  2021cited by this paper
• Metabolic and epigenetic regulation of endoderm differentiation.

  2021cited by this paper
• Expression of Piwi, MMP, TIMP, and Sox during Gut Regeneration in Holothurian Eupentacta fraudatrix (Holothuroidea, Dendrochirotida)

  2021cited by this paper
• Acetate Downregulates the Activation of NLRP3 Inflammasomes and Attenuates Lung Injury in Neonatal Mice With Bronchopulmonary Dysplasia

  2021cited by this paper
• A systematic review of the factors influencing microbial colonization of the preterm infant gut

  2021cited by this paper
• Alterations of the Gut Microbiota in Patients with COVID-19 or H1N1 Influenza

  2020cited by this paper
• Perinatal maternal antibiotic exposure augments lung injury in offspring in experimental bronchopulmonary dysplasia.

  2020cited by this paper
• Human Fetal Lungs Harbor a Microbiome Signature

  2020cited by this paper
• Impact of fecal microbiota transplantation on TGF-β1/Smads/ERK signaling pathway of endotoxic acute lung injury in rats

  2020cited by this paper
• The Gut-Lung Axis in Health and Respiratory Diseases: A Place for Inter-Organ and Inter-Kingdom Crosstalks

  2020cited by this paper
• Utility of volatile organic compounds as a diagnostic tool in preterm infants

  2020cited by this paper
• Intestinal Dysbiosis and the Developing Lung: The Role of Toll-Like Receptor 4 in the Gut-Lung Axis

  2020cited by this paper
• Breast Milk, a Source of Beneficial Microbes and Associated Benefits for Infant Health

  2020influential reference
• Gut Microbiota and Lung Injury.

  2020cited by this paper
• Mechanisms of ATII-to-ATI Cell Differentiation during Lung Regeneration

  2020cited by this paper
• The Ability of Respiratory Commensal Bacteria to Beneficially Modulate the Lung Innate Immune Response Is a Strain Dependent Characteristic

  2020cited by this paper
• Early Gut Microbiota Changes in Preterm Infants with Bronchopulmonary Dysplasia: A Pilot Case–Control Study

  2020influential reference
• Roles of the gut microbiota in the adaptive evolution of mammalian species

  2020cited by this paper
• Links Between Inflammatory Bowel Disease and Chronic Obstructive Pulmonary Disease

  2020cited by this paper
• Malnutrition, poor post-natal growth, intestinal dysbiosis and the developing lung

  2020cited by this paper
• Gut microecology: Why our microbes could be key to our health.

  2020cited by this paper
• Perspectives on Probiotics and Bronchopulmonary Dysplasia

  2020cited by this paper
• Antibiotics as Major Disruptors of Gut Microbiota

  2020cited by this paper
• Metabolomics of bronchopulmonary dysplasia.

  2019cited by this paper
• Changes in the Composition of the Gut Microbiota and the Blood Transcriptome in Preterm Infants at Less than 29 Weeks Gestation Diagnosed with Bronchopulmonary Dysplasia

  2019influential reference
• Human placenta has no microbiome but can harbour potential pathogens

  2019cited by this paper
• Gut microbiota development of preterm infants hospitalised in intensive care units.

  2019cited by this paper
• Platelet activating factor receptor regulates colitis-induced pulmonary inflammation through the NLRP3 inflammasome

  2019cited by this paper
• Microbes, metabolites, and the gut–lung axis

  2019cited by this paper
• Interaction of inhalable volatile organic compounds and pulmonary surfactant: Potential hazards of VOCs exposure to lung.

  2019cited by this paper
• Trait-based community assembly and succession of the infant gut microbiome

  2019cited by this paper
• Lung development and emerging roles for type 2 immunity

  2019cited by this paper
• Airway Microbiome and Development of Bronchopulmonary Dysplasia in Preterm Infants: A Systematic Review

  2019cited by this paper
• Faculty Opinions recommendation of Human placenta has no microbiome but can contain potential pathogens.

  2019cited by this paper
• Gut and Lung Microbiota in Preterm Infants: Immunological Modulation and Implication in Neonatal Outcomes

  2019cited by this paper
• Temporal development of the gut microbiome in early childhood from the TEDDY study

  2018cited by this paper
• Lack of detection of a human placenta microbiome in samples from preterm and term deliveries

  2018cited by this paper
• Development of severe bronchopulmonary dysplasia is associated with alterations in fecal volatile organic compounds

  2018cited by this paper
• Formula versus donor breast milk for feeding preterm or low birth weight infants.

  2018cited by this paper
• Diet, Microbiota and Gut-Lung Connection

  2018influential reference
• Chronic cigarette smoke exposure induces systemic hypoxia that drives intestinal dysfunction.

  2018cited by this paper
• Early airway microbial metagenomic and metabolomic signatures are associated with development of severe bronchopulmonary dysplasia.

  2018cited by this paper
• Urinary 1H-NMR Metabolomics in the First Week of Life Can Anticipate BPD Diagnosis

  2018cited by this paper
• Intestinal microbiota development and gestational age in preterm neonates

  2018cited by this paper
• IL-6 Drives Neutrophil-Mediated Pulmonary Inflammation Associated with Bacteremia in Murine Models of Colitis.

  2018cited by this paper
• A curious connection: Teasing apart the link between gut microbes and lung disease

  2017cited by this paper
• Introduction to the human gut microbiota

  2017cited by this paper
• Probiotic Supplementation in Preterm Infants Does Not Affect the Risk of Bronchopulmonary Dysplasia: A Meta-Analysis of Randomized Controlled Trials

  2017cited by this paper
• Mechanisms and consequences of intestinal dysbiosis

  2017cited by this paper
• Intestinal commensal bacteria mediate lung mucosal immunity and promote resistance of newborn mice to infection

  2017influential reference
• The NANCI–Nkx2.1 gene duplex buffers Nkx2.1 expression to maintain lung development and homeostasis

  2017cited by this paper
• Pulmonary Epithelial TLR4 Activation Leads to Lung Injury in Neonatal Necrotizing Enterocolitis

  2016cited by this paper
• Emerging pathogenic links between microbiota and the gut–lung axis

  2016influential reference
• Human gut colonisation may be initiated in utero by distinct microbial communities in the placenta and amniotic fluid

  2016cited by this paper
• Enrichment of the lung microbiome with gut bacteria in sepsis and the acute respiratory distress syndrome

  2016cited by this paper
• Dynamics and Stabilization of the Human Gut Microbiome during the First Year of Life.

  2015cited by this paper
• Dynamics and Stabilization of the Human Gut Microbiome during the First Year of Life.

  2015cited by this paper
• The Gut-Lung Axis in Respiratory Disease.

  2015cited by this paper

• Early-Life β-Lactam Exposure and the Developing Microbiome: Clinical Relevance and Controversies.

  2026cites this paper
• Neonatal Microbiome: Early Colonization, Preterm Dysbiosis, and Clinical Implications

  2025influential citation