Modulation of chronic obstructive pulmonary disease progression by antioxidant metabolites from Pediococcus pentosaceus: enhancing gut probiotics abundance and the tryptophan-melatonin pathway

ABSTRACT

Chronic obstructive pulmonary disease (COPD), a condition primarily linked to oxidative stress, poses significant health burdens worldwide. Recent evidence has shed light on the association between the dysbiosis of gut microbiota and COPD, and their metabolites have emerged as potential modulators of disease progression through the intricate gut-lung axis. Here, we demonstrate the efficacy of oral administration of the probiotic Pediococcus pentosaceus SMM914 (SMM914) in delaying the progression of COPD by attenuating pulmonary oxidative stress. Specially, SMM914 induces a notable shift in the gut microbiota toward a community structure characterized by an augmented abundance of probiotics producing short-chain fatty acids and antioxidant metabolisms. Concurrently, SMM914 synthesizes L-tryptophanamide, 5-hydroxy-L-tryptophan, and 3-sulfino-L-alanine, thereby enhancing the tryptophan-melatonin pathway and elevating 6-hydroxymelatonin and hypotaurine in the lung environment. This modulation amplifies the secretion of endogenous anti-inflammatory factors, diminishes macrophage polarization toward the M1 phenotype, and ultimately mitigates the oxidative stress in mice with COPD. The demonstrated efficacy of the probiotic intervention, specifically with SMM914, not only highlights the modulation of intestine microbiota but also emphasizes the consequential impact on the intricate interplay between the gastrointestinal system and respiratory health.

GRAPHICAL ABSTRACT

KEYWORDS:

• Microbial metabolites
• oxidative stress
• COPD
• gut-lung axis

Acknowledgments

We appreciate the advice and technical support on the assay of EF₅₀ and Penh from Prof. Wentao Liu (Department of Pharmacology, Institute of Translational Medicine, Nanjing Medical University).

Disclosure statement

No potential conflict of interest was reported by the author(s).

Author contributions

The manuscript was written through the contributions of all authors. All authors have given approval to the final version of the manuscript. The study was designed by Y.Z., J.Y., X.W.Z., and B.W. Experimental work was conducted by Y.T.L., L.J.L., and J.F. Data analysis and figure generation were performed by L.J.L. and Q.T. W.C. and F.J. established COPD models and conducted specific animal experiments. G.T. carried out H&E staining and pathological analysis of tissue biopsy samples. Y.T.L. and Y.Z. were responsible for the original draft preparation, with input from all other authors. The review and editing were performed by L.R.R. J.Y. and X.W.Z.

Data and code availability

RNA-seq data have been submitted to the National Genomics Data Center database platform (https://ngdc.cncb.ac.cn). They are publicly available under accession number PRJCA017484. SOD and CAT data from NCBI-SRA accession number PRJNA853498, representing RNA-seq data from 6 health and 6 patients with acute exacerbations of COPD, were used.

Data and materials availability

All data associated with this study are present in the paper or the Supplementary Materials as well as from the corresponding author upon request.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/19490976.2024.2320283

Additional information

Funding

The studies were supported by the National Natural Science Foundation of China [81971726], the Natural Science Foundation for Distinguished Young Scholars of Hunan Province [2023JJ10029], the China Postdoctoral Science Foundation (2020M670091ZX), and the Nanjing Healthcare Science and Technology Development Special Funded Project [YKK20191; ZKX22062].