Mammalian organs are colonized by overlapping and unique microbiota, representing a complex ecosystem that regulates and trains host innate and adaptive immunity. Disruption or replacement of the resident microflora by invading pathogens causes dysbiosis, often leading to diseases. Recent advances in omics approaches, including metabolomics and lipidomics, have revealed the crucial roles of host and microbial metabolites in health and disease. Local or systemically circulating metabolites derived from the invading pathogen, organ-specific resident microbiota, and gut microbiota contribute to the pathophysiology of major organs, commonly referred to as microbiota-organ axes. Among others, the presence of these microbial and host metabolites include alcohol, amino acids, nucleotides, organic acids, polyols, short-chain fatty acids, and structural components of bacteria and signaling molecules (e.g., quorum sensing small molecules and metabolites) have metabolic implications in disease development and progression. Therefore, an increased understanding of the impact of the crosstalk between host and microbial metabolites within the host tissue microenvironment, host immunity, and host and pathogen metabolism may open avenues for new therapeutic strategies against various diseases.

This Research Topic aims to highlight current knowledge and research trends of bacterial and host metabolites in the context of pulmonary physiology, immunity, and metabolism and how an increased understanding of these metabolites could be exploited to update ongoing and future antibacterial strategies. We welcome the submission of Original Research, Review, Mini-Review, and Opinion articles that cover different aspects of crosstalk between bacterial and host metabolites and how they mutually modulate the outcome of lung health and diseases. This includes, but is not limited to:

1. The virulence roles of bacterial metabolites, including how they mediate evasion, subversion, and modulation of lung innate and adaptive immunity
2. How host metabolites modulate bacterial virulence and determine the success or failure of acute and chronic lung infections
3. How bacterial and host metabolites influence intraspecies and interspecies competition among the pathogens during acute or chronic lung colonization and infection
4. How micronutrient availability (e.g., sugars, amino acids, metals) and their metabolic byproducts regulate the host-pathogen interactions and immune response in the lung microenvironment
5. The influence of bacterial and host metabolites on antibacterial efficacy and the evolution/emergence of tolerance/persistence and resistance in the context of acute and chronic lung infections
6. The influence of host and bacterial metabolites on the molecular and cellular mechanisms of lung tumor microenvironment, cancer initiation, progression, and metastasis
7. Latest technical breakthroughs and new in vitro, ex vivo, animal models to study the mechanisms by which gut and/or lung microbiome and metabolome drive bacterial pathogens-lung interactions
8. The role of bacterial and host metabolites in dictating the pathophysiology development and clinical outcome of acute and chronic lung diseases
9. The most recent discoveries in host and bacterial metabolites to propose bench-to-bedside diagnostic and therapeutic approaches, including interventional ones that boost host metabolite-based immunity for anti-infectious and anti-cancer therapy

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Frontiers in Immunology

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