Faecalibacterium prausnitzii attenuates sepsis-induced acute lung injury via gut-lung axis in murine models
F. prausnitzii administration reduced inflammatory and oxidative stress markers in two murine S-ALI models through the AA-LXA4-Nrf2-HO-1 pathway, with a favorable direction of effect; no evidence of efficacy in humans was generated.
| Outcome | Grade | Direction | Effect | Studies |
|---|---|---|---|---|
| Pulmonary inflammation (inflammatory markers) | D | ▲ Favorable | redução relatada sem IC ou tamanho de efeito reportado | 1 |
| Oxidative stress (Nrf2/HO-1) | D | ▲ Favorable | upregulação relatada sem IC ou tamanho de efeito reportado | 1 |
| Intestinal barrier integrity | D | ▲ Favorable | restauração relatada sem IC ou tamanho de efeito reportado | 1 |
| Butyrate production (SCFAs) | D | ▲ Favorable | aumento relatado sem IC ou tamanho de efeito reportado | 1 |
| LXA4 levels (arachidonic acid metabolism) | D | ▲ Favorable | aumento relatado sem IC ou tamanho de efeito reportado | 1 |
| Gut dysbiosis (relative abundance of F. prausnitzii in humans) | C | ▼ Unfavorable | redução observacional em pacientes S-ALI sem IC reportado | 1 |
| Mortality / primary clinical outcome in humans | D | — Insufficient | não avaliado | — |
Context
Sepsis-induced acute lung injury carries high ICU mortality and lacks targeted pharmacological treatments. The gut-lung axis is an emerging therapeutic target, and F. prausnitzii is a butyrate-producer linked to anti-inflammatory effects in other settings. Reduced abundance of this organism in S-ALI patients prompted this preclinical mechanistic investigation.
What the study showed
F. prausnitzii reduced pulmonary inflammation and oxidative stress in both CLP and LPS models, with increased LXA4 levels and upregulation of Nrf2 and HO-1. Butyrate production and intestinal barrier integrity were restored. Correlation analysis indicated interactions between microbiota, SCFAs, metabolomics, and inflammatory markers. Absolute numbers, 95% CIs, and effect sizes were not reported in the available text.
How it was done
Mixed-design study: observational 16S rRNA analysis in S-ALI patients (sample size not specified) and two murine experimental models (CLP and LPS). Non-targeted metabolomics and microbiota analysis were used mechanistically. Duration of animal experiments not specified in the provided text.
Effect magnitude
Quantitative effect sizes (SMD, 95% CI, absolute values) were not reported in the available extract; statistical significance claims are made without explicit magnitude metrics.
Limitations
Efficacy evidence is restricted to murine models; translation to humans is not demonstrated. Human clinical data are purely observational (no risk-of-bias tool applied, e.g., ROBINS-I). Human and animal sample sizes not reported in the text. The mechanistic pathway (LXA4-Nrf2-HO-1) is associative, not causal — no inhibition or knock-out experiments were described.
In clinical practice
This study provides no basis for clinical use of F. prausnitzii in S-ALI. Clinicians should not modify therapeutic conduct based on these data. The mechanistic hypothesis generated may inform future study protocols.
What is still missing
RCTs or at least controlled human studies in S-ALI patients are required for any clinical inference. Pharmacological or genetic inhibition experiments targeting the LXA4-Nrf2-HO-1 pathway are needed to establish mechanistic causality.