SRP328186 PRJNA746254 Potential celiac disease Potential CD (PCD) is characterized by a positive celiac disease (CD) serology and a normal small intestinal mucosa. This study was to evaluate whether immunological, microbial and lipid signatures could better characterize PCD from CD atrophic, and to gain further insights into basic immune mechanisms involved in the development of intestinal villous atrophy.This study included 17 CD patients, 10 PCD patients and 12 healthy controls (HC). Plasma samples from all participants were collected to analyse free fatty acids (FFAs) and duodenal mucosa samples of patients were collected to evaluate duodenal immune response and tissue microbiota composition.The immunological analysis of duodenal biopsy revealed a lower percentage of CD4 T lymphocytes in the PCD infiltrate compared to CD patients and lymphocytes were detected only in CD patients. The functional characterization of T cells showed clear signs of inflammation in both CD and PCD patients. In addition, PCD patients showed higher percentages of Th17, Th0-Th17, Tregs and lower percentages of Th2 and Th1-Th17 that might contribute to prevent the mucosal damage.The analysis of microbiota composition of CD and PCD duodenal biopsy did not reveal significant alterations between the two conditions. In PCD patients, the overall abundance analysis of serum FFAs showed significant higher levels of isobutyric and octadecanoic acids compared to CD patients and a higher abundance of propionic, butyric, valeric, 2-ethylhexanoic, tetradecanoic, hexadecanoic and octadecanoic acids compared to HC.CD patients showed increased levels of propionic and 2-ethylhexanoic acids and lower abundance of isovaleric and 2-methylbutyric acids than HC.In the present study we found significant differences in the serum profile of FFAs and in the duodenal immunological response between PCD, atrophic CD and HC. Our result may help shed new light on the gut microbiota-host lipid metabolism- axis and duodenal inflammatory response in CD and PCD patients.