The consumption of artificial and low-calorie sweeteners (ASs, LCSs) is an important component of the Western diet. ASs play a role in the pathogenesis of metabolic syndrome, dysbiosis, inflammatory bowel diseases (IBDs), and various inflammatory conditions. Intestinal nutrient-sensing receptors act as a crosstalk between dietary components, the gut microbiota, and the regulation of immune, endocrinological, and neurological responses. This narrative review aimed to summarize the possible effects of ASs and LCSs on intestinal nutrient-sensing receptors and their related functions. Based on the findings of various studies, long-term AS consumption has effects on the gut microbiota and intestinal nutrient-sensing receptors in modulating incretin hormones, antimicrobial peptides, and cytokine secretion. These effects contribute to the regulation of glucose metabolism, ion transport, gut permeability, and inflammation and modulate the gut–brain, and gut–kidney axes. Based on the conflicting findings of several in vitro, in vivo, and randomized and controlled studies, artificial sweeteners may have a role in the pathogenesis of IBDs, functional bowel diseases, metabolic syndrome, and cancers via the modulation of nutrient-sensing receptors. Further studies are needed to explore the exact mechanisms underlying their effects to decide the risk/benefit ratio of sugar intake reduction via AS and LCS consumption.

Autoimmune and immune-mediated inflammatory diseases (IMIDs) develop when genetically and environmentally susceptible hosts lose stable immune tolerance. The gut ecosystem is increasingly recognized as a biologically active interface in this process. Its bacterial, fungal, and viral components may shape mucosal and systemic immunity through antigenic stimulation, barrier regulation, and metabolite-dependent signaling, although the strength of evidence is uneven: bacteriome data are currently the most mature, whereas mycobiome, virome, and phageome findings remain more disease-specific and emerging. Dysbiosis may influence autoimmunity through overlapping routes, including epithelial barrier failure, altered short-chain fatty acid, bile acid, and tryptophan metabolism, molecular mimicry, and cross-kingdom microbial interactions. Nutrition is central to this network because dietary substrates determine microbial growth, metabolic output, epithelial integrity, and immune-cell differentiation. In this narrative review, we integrate evidence on disease-associated bacteriome, mycobiome, and virome patterns in systemic autoimmune diseases, with emphasis on rheumatoid arthritis, systemic lupus erythematosus, Sjögren’s syndrome, systemic sclerosis, spondyloarthritis, vasculitides, and idiopathic inflammatory myopathies. COVID-19 is considered not as a proven causal driver of autoimmunity, but as an example of an environmental and infectious insult capable of perturbing microbiome–barrier–immune communication. Finally, we discuss diet-based and microbiome-targeted approaches, including probiotics, prebiotics, synbiotics, and postbiotics, as adjunctive strategies that may help restore microbial resilience and immune balance. A better understanding of the diet–microbiome–host immunity axis may support more personalized preventive and therapeutic concepts in autoimmune disease.

Immune-mediated inflammatory diseases (IMIDs) arise from interactions among genetic susceptibility, epithelial barrier function, microbiota, diet, and other environmental exposures. Modern diets influence mucosal immunity not only through fibre intake, food processing, and microbiota composition, but also through a less explored exposure layer: plant-derived molecules with potential immune activity. Crop breeding, intensive agriculture, global trade, gluten-free substitutes, and plant-based food technologies have changed the spectrum, dose, concentration, and matrix in which plant defence proteins, antinutritional factors, endogenous toxicants, and novel plant antigens reach the intestinal surface. In this structured, hypothesis-generating narrative review, we propose dietary adjuvanticity as a mechanistic framework for considering how selected food-derived molecules may amplify mucosal immune responsiveness, modify antigen presentation, disturb barrier function, or lower tolerance thresholds without necessarily acting as classical autoantigens. The framework differs from general food-derived immunomodulation, nutritional exposomics, and diet-microbiota-host interaction models by focusing specifically on adjuvant-like immune amplification at the intestinal mucosa. The ASIA concept is used only in Shoenfeld’s functional sense, as an analogy for exogenous immune amplification through innate activation, danger signalling, bystander activation, epitope spreading, and loss of tolerance in susceptible hosts; it is not applied as a dietary diagnosis. Wheat amylase-trypsin inhibitors, gluten epitopes, lectins, potato glycoalkaloids, saponins, quinoa prolamins, emerging legume proteins, L-canavanine, and tolerance-promoting plant substrates are discussed with explicit separation of established clinical evidence, strong mechanistic evidence, preclinical/ex vivo evidence, and speculative disease-modifier hypotheses. Overall, plant-derived exposures are best interpreted as potential modifiers within the IMID exposome, not as primary causes of autoimmunity. Testing this model will require defined exposures, food-matrix and processing studies, biomarkers of barrier and immune activation, patient stratification, and controlled human studies.