Microbiome Interactions in Immune System Function

The mammalian microbiome comprises a diverse consortium of bacteria, archaea, viruses, fungi and other microscopic organisms that colonise epithelial surfaces, notably the gut. These communities co-evolve with the host and play a pivotal role in the development, calibration and execution of both innate and adaptive immunity. Microbial metabolites, structural components and secreted factors shape the maturation of immune organs, influence lymphoid tissue organisation and modulate effector functions of myeloid and lymphoid cells. At mucosal barriers, cross-talk between commensals and host sensors maintains homeostasis, while dysbiosis can precipitate inflammatory disorders or alter susceptibility to infection. Advances in humanised animal models and standardised gnotobiotic systems have begun to unravel causal links between defined microbial consortia and immune outcomes. Environmental exposures, diet and host genetics further interweave with microbial signals to determine immune set-points, with implications for vaccine design, autoimmune disease prevention and the development of microbiome-based therapeutics on a global scale.

Research from Nature Portfolio

Recent studies have demonstrated the power of a humanised mouse model engineered to reconstitute a complete human lymphoid and myeloid system, including organised gut-associated lymphoid tissues. This platform supports class-switch recombination, somatic hypermutation and neutralising antibody responses following microbial and vaccine challenges, thereby offering a robust tool to dissect microbe–immune interactions in vivo. Comparative analyses of wild and laboratory mice have revealed that natural microbial exposures prime myeloid and lymphoid compartments into a more activated state than seen under sterile housing conditions, underscoring the importance of antigenic diversity in immune education. A minimal, defined 15-strain mouse gut microbiota has been established in a standardised gnotobiotic model, reproducing key host physiological and immunological phenotypes of conventional colonies. This simplified community enhances reproducibility and enables targeted investigations into how individual taxa contribute to host immune homeostasis and resilience to nutritional or inflammatory perturbations.

Microbiome Interactions in Immune System Function publication trend

The graph below shows the total number of articles in microbiome interactions in immune system function across all publications each year (not limited to Nature Index journals).

Technical terms

Microbiome: The collective genomes and organisms of all microorganisms inhabiting a particular environment, especially the gut.

Gnotobiotic: Refers to an environment or animal in which all microbial species are known, often used to study defined microbial consortia.

Regulatory T cell (Treg): A subset of CD4⁺ T lymphocytes that maintain immune tolerance and prevent excessive inflammatory responses.

Somatic hypermutation: A process during B cell maturation where point mutations in immunoglobulin genes increase antibody affinity for antigen.

References

1. A humanized mouse that mounts mature class-switched, hypermutated and neutralizing antibody responses. Nature Immunology (2024).
2. The comparative immunology of wild and laboratory mice, Mus musculus domesticus. Nature Communications (2017).
3. A standardized gnotobiotic mouse model harboring a minimal 15-member mouse gut microbiota recapitulates SOPF/SPF phenotypes. Nature Communications (2021).
4. The Mammalian Metaorganism: A Holistic View on How Microbes of All Kingdoms and Niches Shape Local and Systemic Immunity. Frontiers in Immunology (2021).
5. Gut microbiota and lipopolysaccharide content of the diet influence development of regulatory T cells: studies in germ-free mice. BMC Immunology (2008).
6. Rapid environmental effects on gut nematode susceptibility in rewilded mice. PLOS Biology (2018).