Advancing Microbiome Functional Insights through Systems Biology Approaches: Methods, Mechanisms, and Applications

The gut microbiome is a complex ecosystem that influences a wide spectrum of physiological processes, from immune regulation to metabolic health. Understanding its function requires moving beyond static taxonomic profiles to a dynamic, systems-level view of how microbial communities interact with each other, with the host, and with external factors. Recent technological advances enable deep profiling through multi-omics data—such as metagenomics, metabolomics, and transcriptomics—while complementary data sources, including environmental exposures, dietary intake, and immune responses, provide vital context. Systems biology offers a powerful framework to integrate these heterogeneous data types and uncover emergent properties that cannot be understood through single-layer analyses. This integrative perspective is critical for deciphering the gut microbiome’s role in disease mechanisms and health interventions.



This Research Topic seeks to advance a systems biology understanding of the gut microbiome by integrating diverse data modalities—ranging from multi-omics layers to environmental and nutritional factors. Despite growing data availability, key challenges remain in modeling the complexity and interdependence across microbial species, host systems, and external exposures. We invite contributions that develop or apply computational, statistical, or machine learning/artificial intelligence methods to unravel these interactions and elucidate functional mechanisms. A central aim is to bridge high-dimensional data with interpretable biological insights, supporting both hypothesis generation and validation in clinical or experimental settings. This issue is open to studies investigating bacteria, fungi, viruses, and their cross-domain interactions, as well as those incorporating molecular systems, dietary factors, or environmental exposures to gain a more holistic view of microbiome function. We particularly welcome interdisciplinary submissions that link methodological development with biological or translational impact.



We welcome manuscripts in the following themes:

• Integration of metagenomics, metatranscriptomics, metabolomics, and other omics layers to infer microbiome function.

• Linking microbial community activities to host physiology, including immune, metabolic, and neurological responses.

• Investigating cross-domain interactions among bacteria, fungi, and viruses, as well as environmental or dietary influences.

• Applying data integration, network modeling, and machine learning to generate population health insights.

• Contributing review articles that synthesize recent methodological advances in microbiome systems biology.



We also welcome submissions that explore new frontiers in integrative microbiome research beyond the current scope.



We particularly encourage interdisciplinary teams combining computational, experimental, and clinical expertise.

Article types and fees

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

• Brief Research Report
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• ... View all formats

Articles that are accepted for publication by our external editors following rigorous peer review incur a publishing fee charged to Authors, institutions, or funders.

Article types

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

• Brief Research Report
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Review
• Systematic Review

Keywords: Gut microbiome, Systems Biology, Multi-omics integration, Host–microbiome interactions, Functional Analysis

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.