Impact of intestinal dysbiosis on clinical course in severe acute pancreatitis: a multicenter prospective observational study

Background Dysbiosis, an imbalance of the intestinal microbiota in critically ill patients, reportedly contributes to poor outcomes. Controlling the disruption of intestinal homeostasis could be promising tactics for infectious complications in severe acute pancreatitis. To improve the mortality rate of severe acute pancreatitis with high frequency of infectious complications, it is warranted to elucidate the pathophysiology for development of new treatment strategies. We hypothesized that patients with severe acute pancreatitis would demonstrate gut dysbiosis, leading to an onset of infectious complications and poor outcomes. Methods We will conduct a prospective study to compare the sequential changes in intestinal microbiota using 16s RNA metagenomics and metabolomics between patients with severe acute pancreatitis and control patients. We will enroll adult patients (18 years of age or older) diagnosed with severe acute pancreatitis and newly admitted to the intensive care unit (ICU) requiring intensive care for 48 hours or longer. We will exclude patients with inflammatory bowel disease, patients with diarrhea prior to ICU admission, patients who have received antimicrobial agents for more than 1 week in the 2 months prior to admission to the ICU. We will collect stool and blood samples on day 1, 3, and 7. The primary outcome is changes in various parameters of the intestinal microbiota, protein concentration in stool, and metabolite concentration. The secondary outcomes include relationship between each parameter and short- and long-term prognosis, correlation of each parameter with treatment details and clinical course during ICU stay, and associations among the amount of diarrhea and alpha-diversity parameters, protein concentration in each stool, and metabolite concentration. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study is supported by Takeda Science Foundation. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This study was approved by the Institutional Review Board of Chiba University Graduate School of Medicine (approval number: M10499) and conducted in accordance with the Ethical Guidelines for Medical and Health Research Involving Human Subjects in Japan. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors。