Gut microbiomes, host immune response, and organ dysfunction across the gut-lung, gut-brain, and gut-liver axes
This narrative review synthesizes mechanistic associations between gut dysbiosis and distant-organ dysfunction but establishes no causality and provides no quantified effect estimates for any clinical outcome.
| Population | Humans and animal models with gut dysbiosis associated with pulmonary (asthma, COPD, cystic fibrosis, bronchiectasis, pulmonary hypertension, lung cancer), neurological (cognitive impairment, neurodegenerative diseases, Parkinson's), or hepatic diseases (MASLD, fibrosis, oxidative stress, ferroptosis) |
|---|---|
| Intervention | Alterations in gut microbiome composition, microbial metabolites (SCFAs, LPS, peptidoglycans), fecal microbiota transplantation (FMT), and probiotics |
| Comparator | Healthy microbiota or no intervention (variable across cited primary studies) |
| Outcome | Gut microbiome composition in COPD; Lung inflammation and ILC2 response (murine model, butyrate); Intestinal permeability in pulmonary hypertension (animal model); Akkermansia abundance and lung function in cystic fibrosis (children); LPS-induced acute lung injury and FMT (animal model); Cardiac hypertrophy and vascular fibrosis in pulmonary hypertension (propionate, animal model); Gut dysbiosis and gut-brain/gut-liver axes (narrative) |
Summary of findings
| Outcome | Effect | 95% CI | Certainty | Clinical relevance | Notes |
|---|---|---|---|---|---|
| Gut microbiome composition in COPD | no pooled estimate; directional association only (higher Streptococcus in COPD vs controls, in the effect size reported) | — | Very low | — | 1 studies |
| Lung inflammation and ILC2 response (murine model, butyrate) | directional reduction in lung inflammation with butyrate in murine model; in the quantitative effect size or CI reported | — | Very low | — | 1 studies |
| Intestinal permeability in pulmonary hypertension (animal model) | directional association between reduced SCFA-producing bacteria and increased permeability; in the quantitative effect size reported | — | Very low | — | 1 studies |
| Akkermansia abundance and lung function in cystic fibrosis (children) | positive correlation Akkermansia vs FEV1% pred; negative correlation vs calprotectin; in the r-value or CI reported | — | Very low | — | 1 studies |
| LPS-induced acute lung injury and FMT (animal model) | directional reduction in IL-1beta, IL-6, TNF-alpha with FMT via TLR4/NF-kB inhibition; in the quantitative effect size or CI reported | — | Very low | — | 1 studies |
| Cardiac hypertrophy and vascular fibrosis in pulmonary hypertension (propionate, animal model) | directional attenuation of cardiac hypertrophy, fibrosis, vascular dysfunction with propionate; in the quantitative effect size or CI reported | — | Very low | — | 1 studies |
| Gut dysbiosis and gut-brain/gut-liver axes (narrative) | no quantitative effect size; narrative mechanistic associations only | — | Very low | — |
Context
The gut-lung, gut-brain, and gut-liver axes represent bidirectional communication pathways mediated by microbial metabolites, immune signaling, and neuroendocrine routes. Understanding these connections has implications for respiratory, neurological, and hepatic diseases of high prevalence. Integrative reviews are necessary to map the state of knowledge but insufficient to guide clinical interventions without robust primary evidence.
What the study showed
The review describes associations between gut dysbiosis and organ dysfunction across multiple axes. In the gut-lung axis, COPD patients showed higher fecal Streptococcus abundance versus healthy controls, and in murine models butyrate administration reduced lung inflammation and inflammatory ILC2 responses. In the gut-liver axis, reduction of SCFA-producing bacteria was associated with increased intestinal permeability in a pulmonary hypertension model. No effect sizes, 95% CIs, or primary clinical outcome data are reported directly by the review authors; cited figures derive from heterogeneous primary studies.
How it was done
Non-systematic narrative review. A total of 35,211 studies published between 2020 and 2025 were examined across PubMed, Scopus, and ScienceDirect; 88 were selected and only 7 identified for formal analysis. No PROSPERO protocol is registered, no PRISMA checklist is applied, no risk-of-bias assessment of included studies (RoB 2, ROBINS-I, or AMSTAR-2) is performed, and no quantitative meta-analysis is conducted.
Effect magnitude
No pooled effect size is calculated. The review provides no 95% CI, RR, OR, SMD, or MD for any outcome. The actual magnitude of described effects cannot be extracted from this document.
Risk of bias
Narrative review without a registered protocol, no formal risk-of-bias assessment (no AMSTAR-2, RoB 2, or ROBINS-I applied), and selection of only 7 studies from 35,211 identified without transparent inclusion criteria. Heterogeneity of populations (humans and animals), outcomes, and interventions precludes any quantitative synthesis. Confounders acknowledged by the authors themselves (smoking, age, diet, medications, environmental exposures) were not controlled in the primary studies.
What this study does NOT prove
This study does not prove causality between gut dysbiosis and organ dysfunction in any of the three axes analyzed. It does not demonstrate efficacy of any intervention (probiotics, FMT, SCFAs) in human populations with the described conditions.
In clinical practice
This review does not support any change in clinical practice. Clinicians should not use this document to prescribe probiotics, FMT, or SCFA modulation for pulmonary, neurological, or hepatic conditions outside the context of a clinical trial. The described associations are mechanistic hypotheses, not efficacy evidence.
Limitations
Narrative review without a registered protocol, no formal risk-of-bias assessment (no AMSTAR-2, RoB 2, or ROBINS-I applied), and selection of only 7 studies from 35,211 identified without transparent inclusion criteria. Heterogeneity of populations (humans and animals), outcomes, and interventions precludes any quantitative synthesis. Confounders acknowledged by the authors themselves (smoking, age, diet, medications, environmental exposures) were not controlled in the primary studies.
What is still missing
RCTs with pre-specified primary clinical outcomes, confounder control, and adequate follow-up are needed for each organ axis. GRADE-assessed meta-analyses of existing trials must precede any clinical recommendation.
Technical appendix
Version history
- 1.0 · 2026-10-30 — Auto-generated under Evidence Standard v1.0