In Silico Investigation Reveals a Potential Functional Role for Human Microbiome in Chronic Obstructive Pulmonary Disease

Jana, N.; Dhara, O.; Bhattacharya, S. S.

doi:10.1101/2025.06.29.660899

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bioRxiv · 10.1101/2025.06.29.660899

In Silico Investigation Reveals a Potential Functional Role for Human Microbiome in Chronic Obstructive Pulmonary Disease

Jana, N.·Dhara, O.·Bhattacharya, S. S.

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Abstract

Chronic Obstructive Pulmonary Disease (COPD) is a progressive enervating lung disease characterized by chronic inflammation, airway inhibition and unrecoverable structural damage to the lungs. While traditionally associated with environmental factors similar as cigarette smoke and air pollution as well as genetic factors, recent revelations has increasingly indicative of the role of microbiomes in the modulation of this disease. This study explores the structural and functional relations between microbial proteins and human proteins involved in COPD using in-silico bioinformatic tools. Several critical human proteins involved in COPD pathogenesis such as MMP 1, MMP 2, MMP 14, TNF-, TGF-{beta} were evaluated for the presence of microbial homologous proteins using BLAST analysis in the microbial database. The results revealed significant structural homology with microbial proteins from species including E. coli, K.pneumonia, Bacillus thuringiensis, Bifidobacterium samirii. This microbial protein may impact COPD progression through mechanisms similar as molecular belittlement and modulation of host vulnerable responses. Further molecular docking simulations were conducted using the herbal drug oleanolic acid known for their anti-inflammatory effect and can be potentially used in the treatment of COPD. Results demonstrated favourable interactions between these composites and both human and microbial proteins, indicating therapeutic potential of the compounds. For case oleanolic acid showed strong interaction with TNF- and its microbial homolog. Also phylogenetic tree construction using Clustal Omega handed perceptivity into the evolutionary connections between the bacteria hosting homologous proteins, suggesting possible ancestral links and participated functional pathway applicable to COPD pathology. The finding emphasize the possibility of microbiome deduced proteins to act as modifiers in COPD progression as well as the therapeutic potential of the herbal compounds in targeting both host and microbial factors, which need to be further ascertained by in vitro, in vivo, as well as clinical studies. This novel in silico approach offers a unique prospective on COPD treatment by integrating microbiome and phytotherapy laying the groundwork for future personalized therapeutic strategies targeting both microbial and host inflammatory pathways.

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Jana, N., Dhara, O., Bhattacharya, S. S.. 2025-07-03. In Silico Investigation Reveals a Potential Functional Role for Human Microbiome in Chronic Obstructive Pulmonary Disease. https://doi.org/10.1101/2025.06.29.660899

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