Interaction between microbiota and immunity in health and disease Original paper

What was reviewed?

This article reviewed the bidirectional interactions between the commensal microbiota and the host immune system in both health and disease, with a primary focus on mechanistic immune regulation rather than descriptive associations. The authors synthesized evidence from immunology, microbiology, and translational medicine to explain how the microbiome actively trains, calibrates, and sustains innate and adaptive immune functions across the lifespan. The review framed host–microbiome relationships as an evolved mutualistic system, in which immune tolerance, barrier integrity, and controlled inflammation are continuously negotiated. Rather than limiting its scope to the gut, the paper extended the discussion to extra-intestinal organs, highlighting how microbial signals influence immune responses in the skin, lung, liver, and central nervous system. The review also critically addressed methodological challenges, causality gaps, and translational limitations in microbiome–immunity research.

Who was reviewed?

The review integrated findings from studies involving healthy human populations, patients with immune-mediated diseases, and a wide range of experimental animal models, including germ-free and genetically susceptible mice. Human cohorts included individuals with inflammatory bowel disease, autoimmune disorders, cardiometabolic disease, cancer, allergic conditions, and neuroinflammatory disorders. The authors also reviewed studies across key life stages, particularly early infancy, to demonstrate how early microbial exposure shapes immune maturation and long-term disease susceptibility. This broad population base allowed the authors to identify conserved immune–microbiome mechanisms while acknowledging context-specific variation.

What were the most important findings?

The review demonstrated that the microbiome is essential for immune system development, functional specialization, and homeostatic balance. Early-life microbial colonization was shown to be critical for the maturation of gut-associated lymphoid tissue, IgA production, regulatory T cell development, and balanced Th1, Th2, and Th17 responses. Major microbial associations included segmented filamentous bacteria driving Th17 differentiation, Bacteroides fragilis promoting immune tolerance through polysaccharide A, and short-chain fatty acid–producing bacteria supporting regulatory T cell expansion and epithelial integrity. The paper highlighted antimicrobial peptides, mucus layers, IgA, and pattern-recognition receptor signaling as core mechanisms through which immunity shapes microbial compartmentalization. Dysregulation of these interactions was consistently linked to disease states, with reduced microbial diversity and altered taxa associated with inflammatory bowel disease, rheumatoid arthritis, metabolic disease, and cancer. Importantly, the review emphasized that immune dysregulation can both result from and reinforce microbial imbalance, complicating causal inference.

What are the greatest implications of this review?

The most significant implication for clinicians is that immune-mediated diseases cannot be fully understood or treated without accounting for microbiome context. The findings support microbiome-informed therapeutic strategies, including rational microbial consortia, postbiotics, diet-based modulation, and selective microbiome editing, rather than nonspecific immune suppression. Clinically, the review reinforces that preserving microbial diversity and immune–microbiome equilibrium is foundational to immune resilience, treatment response, and long-term disease prevention.