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The Balance of the Microbiome and Human Health: A Molecular Perspective

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Microbiology".

Deadline for manuscript submissions: 30 November 2026 | Viewed by 661

Editor

Prof. Dr. Xinyi Yang

E-Mail Website
Guest Editor
Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
Interests: microbiome–host interactions; molecular mechanisms of pulmonary fibrosis; anti-fibrotic drug discovery; microbial metabolites and immune modulation
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The human microbiome engages in multi-layered molecular dialogs with the host, spanning metabolic cooperation and immune regulation. Advances in sequencing and multi-omics have shifted research from community-level description toward a mechanistic understanding. However, moving beyond correlation to causation remains a key challenge. How do microorganisms influence host functions via specific mediators? How does the host recognize and respond to microbial signals? Which molecular pathways offer druggable targets? Importantly, the balance of the microbiome is fundamental to human health; its disruption, termed dysbiosis, is linked to a wide range of diseases.

Elucidating these mechanisms is essential for translating microbiome research into precision medicine. Deciphering the molecular language between host and microbe enables targeted interventions, including small molecule drugs, engineered probiotics, phage therapies, and personalized nutrition, to restore microbial balance and treat conditions such as metabolic, inflammatory, neoplastic, and fibrotic diseases.

This Special Issue adopts a molecular perspective, integrating bioinformatics and computational biology to uncover underlying mechanisms. It aims to gather cutting-edge research covering molecular interactions and targeted intervention strategies, facilitating the translation of microbiome research into precision medicine.

Closely aligned with the journal’s scope, this Special Issue focuses on the molecular basis of host–microbe interactions, a frontier in biomedical research. By featuring mechanistic studies using advanced technologies such as multi-omics integration, single-cell and spatial analysis, and AI-driven compound screening, it will highlight how molecular insights can drive novel diagnostics and therapeutics. The goal of this Special Issue is to create a comprehensive resource bridging fundamental microbiome biology with clinical applications, reflecting the journal’s commitment to advancing human health.

In this Special Issue, original research articles and reviews are welcome. Research areas may include, but are not limited to, the following:

  1. Molecular Mechanisms and Functional Characterization.

Molecular basis of host-microbe interactions (receptor recognition, metabolite signaling, and barrier regulation), functional characterization of core microbiota (functional groups, key strains, and postbiotics), and molecular pathological mechanisms of dysbiosis in metabolic, immune-inflammatory, and neoplastic diseases.

  1. Precision Intervention Strategies.

Small-molecule drugs targeting microbial pathways, molecular screening and optimization of functional probiotics, effective component analysis of fecal microbiota transplantation, and phage therapy or engineered microorganism design.

We particularly welcome studies that combine computational approaches with experimental validation, bridging in silico predictions with in vitro and in vivo studies.

I look forward to receiving your contributions.

Prof. Dr. Xinyi Yang
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-anonymized peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • host–microbiome interactions
  • molecular mechanisms
  • metabolite signaling
  • multi-omics integration
  • genome-scale metabolic models (GEMs)
  • machine learning
  • spatial microbiome
  • precision intervention
  • microbiome–drug interaction
  • personalized nutrition

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Published Papers (2 papers)

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14 pages, 5490 KB  
Article
Integrated Analysis of the Lung Microbiome and Metabolome Reveals Associations Between Amino Acid Metabolism and Pulmonary Fibrosis in a Bleomycin-Induced Mouse Model
by Chunjie Xu, Siying Qin, Peiyi Sun, Yao Meng, Congran Li, Xiukun Wang, Xuefu You, Guoqing Li and Xinyi Yang
Int. J. Mol. Sci. 2026, 27(13), 5895; https://doi.org/10.3390/ijms27135895 - 30 Jun 2026
Viewed by 101
Abstract
Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive lung disease with limited therapeutic options. To investigate the roles of the pulmonary microbiota and metabolism in fibrosis, we established a bleomycin (BLM)-induced mouse model at 14- and 28-day timepoints and performed integrated 16S [...] Read more.
Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive lung disease with limited therapeutic options. To investigate the roles of the pulmonary microbiota and metabolism in fibrosis, we established a bleomycin (BLM)-induced mouse model at 14- and 28-day timepoints and performed integrated 16S rRNA gene amplicon sequencing and untargeted metabolomic analyses. Histological and Western blot analyses confirmed significant fibrotic changes and the upregulation of fibrotic markers. Microbiome profiling revealed marked dysbiosis after BLM exposure, characterized by reduced microbial diversity and enrichment of Klebsiella. LC-MS–based metabolomic analysis identified substantial perturbations in the lung tissue metabolome, particularly in lipid metabolism, amino acid metabolism, and energy pathways. Correlation analysis indicated a strong positive association between the abundance of Klebsiella and the levels of specific dipeptides, including Ala-Hyp-Gly, Asp-His, and Asp-Asn. The accumulation of these dipeptides may reflect increased collagen degradation and turnover in fibrotic lungs. Collectively, our findings demonstrate that BLM-induced pulmonary fibrosis is accompanied by coordinated alterations in the lung microbiome and metabolome. Notably, microbial dysbiosis, particularly the expansion of Klebsiella, may be associated with alterations in amino acid metabolism and fibrotic progression. Full article
(This article belongs to the Special Issue The Balance of the Microbiome and Human Health: A Molecular Perspective)
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Review

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19 pages, 1066 KB  
Review
Evolutionary Genomics of Human Gut Bacteria: Ecological Plasticity Across the Mutualism–Pathogenicity Spectrum
by Yasmin N. Ramadan, Salwa Q. Bukhari, Zinab Alatawi, Ghaleb Oriquat, Noura H. Abd Ellah, Eltayib Hassan Ahmad Mohamedosman, Rehab Ahmed and Helal F. Hetta
Int. J. Mol. Sci. 2026, 27(11), 5009; https://doi.org/10.3390/ijms27115009 - 1 Jun 2026
Cited by 1 | Viewed by 392
Abstract
The human gut microbiome comprises a diverse community of bacteria whose interactions with the host range from beneficial mutualism to opportunistic pathogenicity. These interactions are shaped by genomic plasticity and ecological pressures that influence whether microbes support host health, remain conditionally harmless, or [...] Read more.
The human gut microbiome comprises a diverse community of bacteria whose interactions with the host range from beneficial mutualism to opportunistic pathogenicity. These interactions are shaped by genomic plasticity and ecological pressures that influence whether microbes support host health, remain conditionally harmless, or contribute to disease. Understanding the mechanisms underlying these shifts is essential for clarifying the balance between cooperation and pathogenicity within the gut ecosystem. This review explores the genomic and evolutionary mechanisms that shape microbial adaptation across the mutualism–pathogenicity spectrum in the human gut. Key processes, including horizontal gene transfer (HGT), host-mediated selection, and niche specialization, enable microbes to acquire, regulate, or retain traits that influence colonization, metabolic function, and virulence. These adaptive mechanisms allow gut bacteria to respond dynamically to ecological pressures such as inflammation, antibiotic exposure, and dietary change, resulting in context-dependent microbial behaviors. The review also considers how concepts from insect endosymbiosis may provide insight into gut microbial adaptation. While both systems exhibit host specialization, major differences in transmission mode, ecological flexibility, and genome evolution limit direct comparisons. Rather than following a fixed progression toward parasitism, gut microbes exhibit flexible adaptive strategies shaped by host and environmental conditions. By integrating ecological and evolutionary perspectives, this review presents a balanced framework for understanding how genomic adaptation influences microbial behavior in the gut. This perspective improves our understanding of dysbiosis and microbial pathogenesis and may support the development of microbiome-informed therapeutic strategies for maintaining host health. Full article
(This article belongs to the Special Issue The Balance of the Microbiome and Human Health: A Molecular Perspective)
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