Gut microbiota analysis of intraductal papillary mucinous neoplasm patients: a step before pancreatic cancer

Abstract

BACKGROUND: Intraductal papillary mucinous neoplasm is currently one of the most frequently diagnosed premalignant lesions of pancreatic cancer. Pancreatic cancer is known to be a major health problem worldwide due to its poor prognosis, and high mortality rates. Research efforts have been focused for years on determining risk factors and risk groups, early diagnosis, possible screening techniques, and improving treatments. Recently, both pancreatic and intestinal microbiota have been linked to pancreatic cancer, its carcinogenesis, and the progression of this pancreatic malignant disease. And it has been hypothesized that gut dysbiosis could be present in the earliest stages of the disease. OBJECTIVE: The aim of this study is to determine which specific bacterial taxonomic changes in the gut microbiota, together with their relative abundances, are present in untreated IPMN patients compared to healthy controls. Investigated by means of a presence/absence study, identifying which bacteria with a relative abundance of less than 5% in healthy controls are present with an abundance of > 15% in IPMN patients, using 16s rRNA sequencing analysis of stool. DESIGN AND SETTING: This study is designed as multicenter, cross-sectional study. It will be performed at Hospital Doctor Josep Trueta de Girona (with the participation of Institut Català de Salut patients and hospitals) over a period of three years and four months. PARTICIPANTS AND METHODS: A total of 415 participants will be enrolled over 1.5 years using a consecutive sampling. This population (meeting inclusion and none of the exclusion criteria) will compromise patients recently diagnosed with IPMN in participating hospitals (83 patients) and their matched controls (332 controls, who have undergone abdominal CT scan for other medical reasons) for age, gender, and hospital. Their microbiota composition and structure will be analysed in faecal samples using 16s rRNA gene sequencing (MiSeq System) to assess the main objective. The primary dependent variable will be the bacterial taxonomy of the microbiota and its relative abundances, which will be compared between both groups. The secondary variables will include the characterization of bacterial taxonomy in IPMN patients and the assessment of alpha diversity in both groups. Additionally, certain covariates have been included