A systems biology approach to understand gut microbiota and host metabolism in morbid obesity: design of the BARIA Longitudinal Cohort Study
Journal article, 2021
Introduction: Prevalence of obesity and associated diseases, including type 2 diabetes mellitus, dyslipidaemia and non-alcoholic fatty liver disease (NAFLD), are increasing. Underlying mechanisms, especially in humans, are unclear. Bariatric surgery provides the unique opportunity to obtain biopsies and portal vein blood-samples. Methods: The BARIA Study aims to assess how microbiota and their metabolites affect transcription in key tissues and clinical outcome in obese subjects and how baseline anthropometric and metabolic characteristics determine weight loss and glucose homeostasis after bariatric surgery. We phenotype patients undergoing bariatric surgery (predominantly laparoscopic Roux-en-Y gastric bypass), before weight loss, with biometrics, dietary and psychological questionnaires, mixed meal test (MMT) and collect fecal-samples and intra-operative biopsies from liver, adipose tissues and jejunum. We aim to include 1500 patients. A subset (approximately 25%) will undergo intra-operative portal vein blood-sampling. Fecal-samples are analyzed with shotgun metagenomics and targeted metabolomics, fasted and postprandial plasma-samples are subjected to metabolomics, and RNA is extracted from the tissues for RNAseq-analyses. Data will be integrated using state-of-the-art neuronal networks and metabolic modeling. Patient follow-up will be ten years. Results: Preoperative MMT of 170 patients were analysed and clear differences were observed in glucose homeostasis between individuals. Repeated MMT in 10 patients showed satisfactory intra-individual reproducibility, with differences in plasma glucose, insulin and triglycerides within 20% of the mean difference. Conclusion: The BARIA study can add more understanding in how gut-microbiota affect metabolism, especially with regard to obesity, glucose metabolism and NAFLD. Identification of key factors may provide diagnostic and therapeutic leads to control the obesity-associated disease epidemic.
obesity
bariatric surgery
metabolites
gut microbiota
insulin resistance
Author
C. C. Van Olden
University of Amsterdam
A. W. Van de Laar
Spaarne Hospital
A. S. Meijnikman
University of Amsterdam
Spaarne Hospital
O. Aydin
Spaarne Hospital
University of Amsterdam
N. Van Olst
Spaarne Hospital
University of Amsterdam
J. B. Hoozemans
University of Amsterdam
L. M. De Brauw
Spaarne Hospital
S. C. Bruin
Spaarne Hospital
Y. I.Z. Acherman
Spaarne Hospital
J. Verheij
University of Amsterdam
J. E. Pyykkö
University of Groningen
M. Hagedoorn
University of Groningen
R. Sanderman
University of Groningen
N. C. Bosma
University of Amsterdam
Valentina Tremaroli
University of Gothenburg
A. Lundqvist
University of Gothenburg
L. E. Olofsson
University of Gothenburg
H. Herrema
University of Amsterdam
Dimitra Lappa
Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology
S. Hjorth
University of Copenhagen
Jens B Nielsen
Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology
T. Schwartz
University of Copenhagen
A. K. Groen
University of Amsterdam
M. Nieuwdorp
University of Amsterdam
Fredrik Bäckhed
University of Gothenburg
University of Copenhagen
Sahlgrenska University Hospital
V. E.A. Gerdes
Spaarne Hospital
University of Amsterdam
Journal of Internal Medicine
0954-6820 (ISSN) 1365-2796 (eISSN)
Vol. 289 3 340-354Subject Categories
Endocrinology and Diabetes
Other Clinical Medicine
Gastroenterology and Hepatology
DOI
10.1111/joim.13157
PubMed
32640105