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Chronic obstructive pulmonary disease (COPD) affects millions of people worldwide and remains a major cause of disease burden and mortality. Although current treatments can reduce symptoms and slow disease progression, few therapies directly address the underlying tissue damage associated with COPD. This has prompted researchers to investigate therapies that target the processes driving disease progression.
One area of growing interest is the gut-lung axis. This bidirectional communication network links intestinal microbial communities with respiratory health through immune signalling and microbial metabolites such as short-chain fatty acids (SCFAs).
A recent study by Kim et al, 2026, investigated whether members of the gut microbiota could be identified as potential therapeutic candidates for COPD using a personalised pharmaceutical meta-analytical screening (PMAS) platform. The researchers developed a screening pipeline using microbiomes derived from patients with severe emphysema (a major subtype of COPD) to identify strains capable of increasing SCFA production within COPD-derived microbiomes. The PMAS platform combines donor-derived microbiomes with gut-mimetic cultivation conditions to evaluate strain-specific effects on metabolite production.
Following a multi-stage screening process, three candidate strains were selected for PMAS evaluation: Lactobacillus fermentum HEM20792, Lactobacillus sakei HEM20224 and Lactobacillus curvatus HEM20382. L. fermentum and L. sakei increased SCFA production relative to control cultures, with L. fermentum producing the strongest overall response.
Unlike conventional probiotic screening approaches, candidate strains were evaluated within microbiomes derived directly from patients with severe COPD. Donor specific microbiome cultures were established using faecal samples from twelve patients with severe COPD. Candidate strains were added to donor microbiome cultures and incubated for 24 hours under anaerobic conditions within a Whitley A95 Workstation.
L. fermentum and L. sakei were subsequently evaluated in a smoke-induced emphysema model. L. fermentum reduced emphysematous changes, improved pulmonary function and reduced inflammatory cell infiltration. L. fermentum also influenced inflammatory responses within the lung. Treatment reduced macrophage populations associated with disease progression and attenuated increases in inflammatory immune cells. Transcriptomic analysis also revealed changes in several pathways associated with inflammation, including NF-κB, arachidonic acid and IL-17 signalling.
Analysis of faecal microbiota and SCFA concentrations provided further support for a gut-lung mechanism. Mice receiving L. fermentum exhibited increased faecal SCFA concentrations alongside shifts in microbial community composition, suggesting that modulation of the gut microbiome may contribute to the observed effects in the lung. The authors also performed a complementary butyrate supplementation experiment, which similarly reduced emphysematous changes and inflammatory markers, supporting a potential role for SCFAs in the observed effects.
Using donor-derived microbiomes cultured under anaerobic conditions, the PMAS platform identified L. fermentum as a strain capable of increasing SCFA production and reducing disease severity in a preclinical COPD model. Although clinical validation is still required, the study also highlights the value of anaerobic cultivation systems for investigating host-associated microbiomes under conditions that more closely reflect the gut environment.
Written by DWS Microbiologist, Eleanor Burke
References:
1. Kim NH, Oh J, Lee JH et al. (2026) A colon mimetic screening approach reveals Lactobacillus fermentum as a microbiome-based therapy for COPD. npj Biofilms and Microbiomes. https://doi.org/10.1038/s41522-026-00978-w
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