Abstract
BACKGROUND: Chronic pancreatitis is a risk factor for pancreatic cancer. Autoimmune pancreatitis is a unique form of chronic pancreatitis that is primarily characterized by its immune mediate etiology, clinically resembling pancreatic cancer, yet uniquely responsive to steroid treatment. OBJECTIVE: Early and accurate diagnosis of autoimmune pancreatitis is vital for effective treatment and patient prognosis, for which new diagnostic tools are urgently required. Gut microbiota dysbiosis has been identified to correlate with the development of pancreatic diseases, which provides new opportunities for the discovery of disease biomarkers. METHODS: We utilized a mass spectrometric global metabolomics investigation of patient autoimmune pancreatitis and chronic pancreatitis fecal samples, investigating microbiome, dietary and human metabolism. RESULTS: We discovered a series of newly identified metabolic signatures between both patient groups including enterolactone, 4-guanidinobutanoic acid, and methylthioadenosine sulfoxide. Additionally, the analysis revealed significant differences in several metabolic pathways such as fatty acids, alkaloids, amino acids and peptides. CONCLUSION: Our observations provide novel insights into important metabolic human pathways and microbiome-derived metabolites to distinguish autoimmune pancreatitis from chronic pancreatitis. These findings reveal systemic metabolic responses and the identified metabolites may be developed into potential biomarkers for future diagnosis to distinguish between autoimmune pancreatitis and chronic pancreatitis.