Gut-derived signals in type 2 diabetes–associated dry eye: current evidence, causal uncertainty, and validation priorities

Type 2 diabetes mellitus (T2DM)-associated dry eye disease (DED) includes aqueous, evaporative, epithelial, inflammatory, and neurosensory phenotypes. Intestinal dysbiosis may contribute to some of these abnormalities, but the clinical and mechanistic evidence has not yet been synthesised in terms of disease relevance and causal strength. We conducted a structured narrative review using iterative PubMed searches, full-text retrieval from PubMed Central and publisher websites, and backward citation tracing. The evidence pool was updated to 26 July 2026. Human studies in T2DM consistently report neuropathy, corneal sensory or nerve changes, meibomian dysfunction, and lacrimal injury, but no human study jointly measuring intestinal microbiota or gut-derived metabolites with T2DM-DED outcomes was found. One disease-matched animal study linked a probiotic–prebiotic intervention with changes in intestinal, lacrimal, inflammatory, and dry-eye-like features. Other experimental models support microbiota-sensitive lacrimal responses, macrophage-dependent corneal nerve repair, and short-chain fatty acid (SCFA)-responsive ocular-surface homeostasis. Taken together, these findings establish model-specific effects rather than a continuous human pathway. SCFAs are therefore considered a hypothesis-prioritised candidate based on cross-model breadth, although their necessity, sufficiency, and mediation in T2DM-DED remain unknown. Diet, glycaemic control, obesity, renal function, neuropathy, medicines, and ocular treatment are important clinical confounders. Future studies should combine longitudinal human co-phenotyping with a disease-matched mediation experiment that measures intestinal, metabolic, lacrimal, corneal-neural, and ocular-surface outcomes in the same temporal sequence. Oral Chinese herbal medicine is presented only as one standardisable perturbation for such testing, rather than as an established gut-mediated therapy.