Diet-Induced Alteration of Microbiota and Development of Obesity, Nonalcoholic Fatty Liver Disease, and Diabetes: Study Protocol of a Prospective Study

Martine Uittenbogaart*, Wouter K. G. Leclercq, Danielle Bonouvrie, Marleen M. Romeijn, Arijan A. P. M. Luijten, Steven W. M. Olde Damink, Francois M. H. van Dielen, Sander S. Rensen

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Background: Development of obesity and obesity-related diseases, such as type 2 diabetes mellitus and nonalcoholic fatty liver disease (NAFLD), is associated with altered gut microbiota composition. The aim of this study is to investigate associations among dietary compounds, intestinal cell function, and gut microbiota composition. We hypothesize that dietary lipid intake is associated with Paneth cell and goblet cell properties that affect gut microbiota composition. Objective: The primary objective of this study is to determine whether a difference in dietary intake is associated with a difference in intestinal mucin-2 expression and gut microbiota composition. Methods: This is a single-center prospective study, including 1 obese group undergoing laparoscopic Roux-en-y gastric bypass and 2 lean control groups undergoing either laparoscopic cholecystectomy or upper gastrointestinal endoscopy (n=228). During laparoscopy, biopsies will be taken of visceral fat (omentum majus), liver, muscle tissue of the abdominal wall, and subcutaneous fat. In the obese group, a small segment of the jejunum will be collected for analysis, which will be compared with an endoscopically derived jejunal biopsy from the upper gastrointestinal endoscopy control group. Stool samples for microbiota profiling will be collected at baseline and 1 year after surgery. Primary outcomes are fecal microbiota composition and mucus characteristics. Secondary outcomes include Paneth cell phenotype, body weight, diet composition, glucose tolerance, resolution of comorbidities, and weight loss 1 year after surgery. Results: This trial is currently open for recruitment. The anticipated completion date is December 2019. Conclusions: The Diet-Induced Alteration of Microbiota and Development of Obesity, NAFLD, and Diabetes study will improve insight into the pathophysiology of obesity and its associated metabolic disorders. Better understanding of weight loss failure and weight regain following bariatric surgery might also behold new therapeutic oppowortunities for obesity and obesity-related comorbidities.

Original languageEnglish
Article numbere11553
Pages (from-to)1-6
Number of pages6
JournalJMIR Research Protocols
Issue number6
Publication statusPublished - 1 Jun 2019


  • microbiota
  • type 2 diabetes
  • obesity
  • gastric bypass


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