Mechanistic insight into the gut microbiome and its interaction with host immunity and inflammation Original paper

What was reviewed?

This article reviewed mechanistic evidence explaining how the gut microbiome shapes host immunity and inflammation through direct microbial signals, microbial metabolites, and host immune sensing pathways. The authors synthesized findings from microbiology, immunology, and inflammatory disease research to show that gut microbes are not passive residents but active regulators of immune organ development, innate immune defense, adaptive immunity, and inflammatory balance. The review positioned the gut microbiome as a core component of immune system maturation and function, emphasizing that immune competence depends on continuous microbial–host crosstalk rather than sporadic pathogen encounters. A central theme was that immune dysregulation and chronic inflammation arise when this dialogue is disrupted, most commonly through dysbiosis, antibiotic exposure, or early-life microbial deprivation.

Who was reviewed?

The review integrated evidence from human populations and animal models to provide a comprehensive mechanistic framework. Human data included observational and clinical studies involving healthy individuals, infants, patients with inflammatory bowel disease, autoimmune disorders, obesity, and chronic inflammatory conditions. These findings were paired with mechanistic studies in germ-free mice, antibiotic-treated animals, gnotobiotic systems, and targeted microbial colonization experiments. By comparing germ-free and conventionally colonized hosts, the reviewed studies demonstrated causal roles for microbiota in immune development and inflammatory control rather than simple associations.

What were the most important findings?

The review demonstrated that gut microbiota drive immune organ maturation, particularly the thymus, spleen, gut-associated lymphoid tissue, Peyer’s patches, and isolated lymphoid follicles, all of which remain underdeveloped in germ-free hosts. Major microbial associations included Firmicutes and Bacteroidetes, which together accounted for approximately 90% of intestinal microbes and served as dominant regulators of immune homeostasis. Specific taxa such as Bifidobacterium, Lactobacillus, Bacteroides thetaiotaomicron, Faecalibacterium prausnitzii, Clostridium species, and segmented filamentous bacteria were repeatedly linked to immune modulation. Microbial metabolites, especially short-chain fatty acids including acetate, propionate, and butyrate, emerged as central signaling molecules that enhanced epithelial barrier integrity, suppressed NF-κB–driven inflammation, promoted regulatory T cell differentiation, and balanced Th17 responses. The review highlighted that microbiota-induced antimicrobial peptides, mucus production, IgA secretion, and tight junction reinforcement collectively form a multilayered immune barrier. Dysbiosis consistently correlated with increased inflammatory cytokines such as TNF-α, IL-6, and IL-1β, along with reduced anti-inflammatory signaling mediated by IL-10 and TGF-β. These shifts were linked to inflammatory bowel disease, metabolic inflammation, autoimmune disorders, and impaired immune tolerance.

What are the greatest implications of this review?

The key implication for clinicians is that immune dysfunction and chronic inflammation frequently reflect disrupted microbiome–immune signaling rather than intrinsic immune defects. The review supports microbiome-targeted strategies as foundational tools for preventing and treating inflammatory diseases, reinforcing the importance of preserving microbial diversity, restoring beneficial taxa, and supporting metabolite-driven immune regulation.