Microbe-immune crosstalk: microbial metabolites and molecules in immune regulation, evasion, and therapy

The host immune system constantly interacts with its microbial communities, which are known as the microbiome. These interactions are driven by diverse microbial molecules that play a central role in shaping immune responses. A wide range of metabolites—including short-chain fatty acids, secondary bile acids, and microbial-derived peptides—can modulate inflammation, tolerance, and tissue repair. Conversely, virulence factors produced by certain pathogens promote immune evasion and, consequently, persistent infections that are often difficult to treat. Advances in multi-omics technologies, germ-free and gnotobiotic models, and metabolite profiling have provided deeper insights into these complex host–microbe interactions. Microbe–Immune crosstalk bridges microbiology, immunology, and translational medicine to shed light on how microbial molecules orchestrate immune function. Understanding these dynamics will provide opportunities for therapeutic interventions, including microbiome modulation, metabolite-targeted therapies, and innovative immunomodulatory strategies, ultimately improving the management of immune-mediated diseases and enhancing host defense.

Despite growing evidence that microbial metabolites and molecules play critical roles in immune regulation, major gaps remain in understanding how to manipulate these interactions for therapeutic benefit. Key challenges include elucidating how microbial-derived molecules shape innate and adaptive immunity, how pathogens exploit them to evade host defenses, and how immune function can be restored or modulated in disease. Advances in multi-omics, metabolite profiling, high-resolution imaging, and germ-free or gnotobiotic models are helping to unravel complex host-microbe interactions. Interdisciplinary approaches integrating microbiology, immunology, and translational medicine offer powerful tools to address these questions. Combining mechanistic studies with computational modeling and microbiome-targeted interventions, researchers can harness microbial molecules to develop innovative immunotherapies, improve infection control, and enhance treatment of immune-mediated diseases.

This Research Topic explores the roles of microbial metabolites and molecules in immune regulation, evasion, and therapeutic modulation. We welcome contributions that provide mechanistic insights into how microbial-derived molecules interact with innate and adaptive immunity and explore their potential for therapeutic applications. Specific themes of interest include:
• Mechanisms by which microbial metabolites and molecules shape immune responses, inflammation, tolerance, and tissue repair
• Pathogen strategies that exploit microbial molecules to evade host defenses
• Microbiome-targeted interventions and metabolite-based therapeutics
• Novel immunomodulatory strategies leveraging microbial molecules
• Multi-omics approaches, metabolite profiling, and computational modeling of host-microbe interactions
• Use of germ-free, gnotobiotic, or other advanced experimental models to study microbial-immune crosstalk
• Translational studies linking microbial molecules to immune-mediated disease prevention or therapy

This Research Topic aims to integrate microbiology, immunology, and translational medicine, advancing our understanding of microbial-immune interactions and their therapeutic potential.

Article types and fees

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Case Report
• Classification
• Clinical Trial
• Editorial
• FAIR² Data
• FAIR² DATA Direct Submission
• Hypothesis and Theory
• Methods
• ... View all formats

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Article types

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Case Report
• Classification
• Clinical Trial
• Editorial
• FAIR² Data
• FAIR² DATA Direct Submission
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Review
• Systematic Review
• Technology and Code

Keywords: Microbial metabolites, Microbiome, Immune regulation, Immune evasion, Immunomodulation, Host-microbe interactions, Microbiome-targeted therapy, Translational immunology

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.