The Diet-Microbiome-Immune Axis: Modulating Gut-Organ Crosstalk

The gut mucosa is no longer viewed merely as a site of digestion and defense; it is now recognized as a central orchestrator of systemic immunity. While the microbiome’s role in shaping intestinal homeostasis is well established, recent evidence reveal its extensive reach across both mucosal and systemic compartments. By establishing dynamic "gut-organ axes," the gut microbiota actively modulate immune responses in distant sites, including the lungs, liver, skin, and brain. When this delicate mucosal-systemic dialogue is disrupted, often exacerbated by Westernized diets or microbial dysbiosis, it can trigger or worsen extra-intestinal inflammatory, autoimmune, and allergic cascades. Fortunately, this axis is modifiable. Dietary interventions, ranging from precision prebiotic and probiotic supplementation to whole-diet modifications, can restructure the microbial community. More importantly, these shifts alter the production of bioactive metabolites (e.g., short-chain fatty acids, secondary bile acids, tryptophan derivatives). Once translocated across the epithelial barrier, these molecules circulate systemically to reprogram immune cell toward distinct phenotypes in peripheral tissues. Despite this potential, the exact molecular pathways bridging nutritional intake microbial metabolism, and distal immune modulation remain fragmented. Addressing this knowledge gap is critical for advancing from generalized dietary advice to precision nutrition.This Research Topic seeks to decode the complex mechanistic pathways linking diet and the microbiome to systemic immune regulation. Rather than observational or correlational studies, our primary objective is to highlight research that establishes a causal relationship: how specific nutrient intake drive predictable changes in microbial signaling, which in turn modulate immune cell function and inflammatory status in extra-intestinal tissues. By bringing together cutting-edge findings in this space, we aim to map the molecular mechanism of the gut-organ axis. Ultimately, this collection will help identify novel dietary strategies, microbial targets, and metabolite-based biomarkers for the prevention and targeted therapeutic management of systemic immune-mediated diseases. We invite researchers to contribute original research, comprehensive reviews, and translational studies. To fit within the scope of this collection, submissions should maintain a clear focus on the immunological interplay between the gut and at least one distal organ or systemic network. Areas of interest include, but are not limited to: - Evaluations of how dietary strategies modulate distal immunity via established gut-organ axes.- Investigations into gut-derived molecules acting as systemic immunological messengers.- Studies tracing gut-primed immune cell trafficking regulated by nutritional factors or microbiota-derived metabolites, and their subsequent homing to peripheral tissues.- Cohort studies exploring diet-microbiome-immune networks in patients with extra-intestinal inflammatory, allergic, or autoimmune conditions.- Research utilizing gnotobiotic murine models, isotope tracing, or micro-physiological systems to establish causality within the diet-microbiome-immune cascade. Topic editors: Bowen Li, Yang Yuhui, Francesca Bottacini Source: https://www.frontiersin.org/research-topics/84269/the-diet-microbiome-immune-axis-modulating-gut-organ-crosstalk