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Chronic pancreatitis (CP) is characterized by abdominal pain, recurrent hospitalizations, frequent exposure to antibiotics, nutritional deficiencies, and chronic opioid use. Data describing the gut microbial community structure of patients with CP is limited. We aimed to compare gut microbiota of a group of patients with severe CP being considered for total pancreatectomy with islet autotransplantation (TPIAT) with those of healthy controls and to associate these differences with severity of clinical symptoms.