Humans and the gut microbiota exist in a symbiotic relationship: the nutrients consumed by the host serve as substrates for gut microbes, and in turn, the diverse metabolites produced by these microbes contribute to maintaining immune homeostasis. Although it is well established that nutritional imbalances—such as high-fat, high-sugar, high-salt diets, or etc.—can lead to cancer, autoimmune diseases, and even psychiatric disorders, much remains to be elucidated regarding how gut microbial metabolites are altered under these conditions and what roles they play. Our research aims to investigate how the gut microbiota and their metabolites change in states of nutritional imbalance, and how these changes regulate T cells to ultimately influence disease development.

Acidity, or pH, is tightly regulated at the cellular, tissue, and systemic levels. This regulation is maintained through H⁺ transport mediated by proteins such as NHE1, H⁺-ATPase, and MCTs (SLC16 family), as well as through the carbonic acid–bicarbonate buffering system controlled by carbonic anhydrases (CAs). However, under pathological conditions, pH homeostasis is disrupted by intrinsic and extrinsic factors, leading to altered proton levels—phenomena that are well documented in diseases such as cancer and inflammatory bowel disease. Our research aims to elucidate how these changes in proton levels, resulting from disrupted pH homeostasis, regulate T cells—either by directly modulating intracellular signaling pathways or by influencing signaling through cell surface receptors—and ultimately impact disease development.

T cells serve as a powerful defense mechanism that protects the body from a wide range of pathogens; however, when dysregulated, they can instead drive or exacerbate disease. Autoimmune diseases are a representative class of disorders caused by T cell dysfunction, often arising when pro-inflammatory T helper 17 (Th17) cells are induced or when immunosuppressive regulatory T (Treg) cells are diminished due to genetic and/or environmental factors. Our research aims to identify diverse therapeutic modalities—including natural products, small-molecule inhibitors, and PROTACs—that modulate the generation of Th17 and Treg cells. To achieve this, we employ a fluorescence-based reporter system combined with high-content imaging screening.