Microbial Influence on Immune System Dynamics

The human immune system is in constant dialogue with a vast ecosystem of microorganisms that colonise mucosal surfaces, most prominently the gut. Beneficial commensals, opportunistic pathobionts and dietary inputs converge to shape the development, differentiation and function of innate and adaptive immune cells. Microbial metabolites such as short-chain fatty acids (SCFAs) and microbial antigens modulate antigen-presenting cells, influence T-cell lineage commitment and maintain barrier integrity. Dysbiosis of the microbiota can lead to inappropriate activation of pro-inflammatory pathways, loss of regulatory mechanisms and heightened susceptibility to metabolic and inflammatory disorders. Recent advances have begun to unravel the molecular crosstalk by which specific bacterial taxa and their products calibrate key immune axes, including the balance between T helper 17 (Th17) cells and regulatory T (Treg) cells, the activity of dendritic cell subsets and the production of cytokines such as transforming growth factor-β (TGF-β) and interleukin-17. These insights carry global significance for novel therapeutic and dietary interventions aimed at restoring immune homeostasis in conditions ranging from inflammatory bowel disease to metabolic syndrome.

Research from Nature Portfolio

Short-term dietary supplementation with fermentable fibres has been shown to counteract high-fat-diet-induced immune and metabolic dysregulation. Fermentable fructooligosaccharides preserved populations of RORγt-expressing CD4+ T cells, including peripherally induced Tregs and Th17 cells, by sustaining a fibre-dependent microbial community and engaging type 2 conventional dendritic cells to improve glucose tolerance. In parallel, investigations into microbial metabolites have demonstrated that butyrate secreted by commensal Clostridiales activates TGF-β1 expression in intestinal epithelial cells. This effect operates through histone deacetylase inhibition and recruitment of the transcription factor SP1, thereby promoting a tolerogenic milieu conducive to Treg accumulation at the mucosal interface. Together these studies illustrate how dietary components and microbial metabolites cooperate to reinforce immune regulation and barrier function.

Microbial Influence on Immune System Dynamics publication trend

The graph below shows the total number of articles in microbial influence on immune system dynamics across all publications each year (not limited to Nature Index journals).

Technical terms

Dysbiosis: An imbalance in the composition or function of microbial communities associated with disease.

Th17 cells: A subset of CD4+ T helper cells that produce interleukin-17 and contribute to barrier defence and inflammation.

Regulatory T cells (Tregs): A population of CD4+ T cells that suppress excessive immune responses and maintain tolerance.

Short-chain fatty acids (SCFAs): Microbial fermentation products (e.g., butyrate) that influence host immune and metabolic processes.

References

1. Fructooligosaccharides benefits on glucose homeostasis upon high-fat diet feeding require type 2 conventional dendritic cells. Nature Communications (2024).
2. Diet prevents the expansion of segmented filamentous bacteria and ileo-colonic inflammation in a model of Crohn’s disease. Microbiome (2023).
3. The Intestine Harbors Functionally Distinct Homeostatic Tissue-Resident and Inflammatory Th17 Cells. Immunity (2019).
4. Butyrate produced by gut commensal bacteria activates TGF-beta1 expression through the transcription factor SP1 in human intestinal epithelial cells. Scientific Reports (2018).
5. Defined microbiota transplant restores Th17/RORγt+ regulatory T cell balance in mice colonized with inflammatory bowel disease microbiotas. Proceedings of the National Academy of Sciences of the United States of America (2020).