Effects of High Inorganic Phosphorus Diet on Intestinal Mucosal Injury and Immune Disfunction in Mice

Background: /Objectives: Excessive dietary inorganic phosphate (Pi) as a food additive poses potential health risks. Methods: This study investigates its impact on intestinal and immune homeostasis in mice using gradient Pi exposure combined with an inflammatory model. Results: Pi overload induced atrophy in the thymus, spleen, and kidney, damaged the intestinal barrier, reduced villus height‑to‑crypt depth ratio, and decreased goblet cell numbers. Altered levels of serum sIgA and IgE, as well as intestinal IgA, IgG, IgE, and IgM, together with decreased IFNα, indicated disrupted immune balance caused by Pi treatment. Proteomic analysis revealed differential expression of key proteins, including CNTFR and Bcl2l1 in the JAK‑STAT pathway, and metabolic regulators CPT1α and IDH1, compared Pi treated mice with the control group. Conclusions: These findings suggest Pi may affect immune and neuronal functions through tumor‑related signaling and mitochondrial pathways, providing insight into the health implications of Pi overconsumption.