Journal Article

Donor metabolic characteristics drive effects of faecal microbiota transplantation on recipient insulin sensitivity, energy expenditure and intestinal transit time

Khan, Muhammad Tanweer, de Groot, Pieter, Scheithauer, Torsten, Bergman, Jacques JGHM, Hoekstra, Joost B L, de Brauw, Maurits, Holleman, Frits, Gerdes, Victor E, Schimmel, Alinda W M, Levels, Johannes H M, Bäckhed, Fredrik, Serlie, Mireille J M, Groen, Albert, Prodan, Andrei, Sales, Amber, Nieuwdorp, Max, Herrema, Hilde, Levin, Evgeni, Ackermans, Mariette, Ståhlman, Marcus, Dallinga-Thie, Geesje, Bakker, Guido J

2020

Overview

ObjectiveBariatric surgery improves glucose metabolism. Recent data suggest that faecal microbiota transplantation (FMT) using faeces from postbariatric surgery diet-induced obese mice in germ-free mice improves glucose metabolism and intestinal homeostasis. We here investigated whether allogenic FMT using faeces from post-Roux-en-Y gastric bypass donors (RYGB-D) compared with using faeces from metabolic syndrome donors (METS-D) has short-term effects on glucose metabolism, intestinal transit time and adipose tissue inflammation in treatment-naïve, obese, insulin-resistant male subjects.DesignSubjects with metabolic syndrome (n=22) received allogenic FMT either from RYGB-D or METS-D. Hepatic and peripheral insulin sensitivity as well as lipolysis were measured at baseline and 2 weeks after FMT by hyperinsulinaemic euglycaemic stable isotope (2H2-glucose and 2H5-glycerol) clamp. Secondary outcome parameters were changes in resting energy expenditure, intestinal transit time, faecal short-chain fatty acids (SCFA) and bile acids, and inflammatory markers in subcutaneous adipose tissue related to intestinal microbiota composition. Faecal SCFA, bile acids, glycaemic control and inflammatory parameters were also evaluated at 8 weeks.ResultsWe observed a significant decrease in insulin sensitivity 2 weeks after allogenic METS-D FMT (median rate of glucose disappearance: from 40.6 to 34.0 µmol/kg/min; p<0.01). Moreover, a trend (p=0.052) towards faster intestinal transit time following RYGB-D FMT was seen. Finally, we observed changes in faecal bile acids (increased lithocholic, deoxycholic and (iso)lithocholic acid after METS-D FMT), inflammatory markers (decreased adipose tissue chemokine ligand 2 (CCL2) gene expression and plasma CCL2 after RYGB-D FMT) and changes in several intestinal microbiota taxa.ConclusionAllogenic FMT using METS-D decreases insulin sensitivity in metabolic syndrome recipients when compared with using post-RYGB-D. Further research is needed to delineate the role of donor characteristics in FMT efficacy in human insulin-resistant subjects.Trial registration numberNTR4327.

• Publisher: BMJ Publishing Group Ltd and British Society of Gastroenterology,BMJ Publishing Group LTD,BMJ Publishing Group
• Subject: Adipose tissue / Adult / Aged / Bile / bile acid metabolism / Bile acids / Bile Acids and Salts - analysis / Chemokine CCL2 - blood / Chemokine CCL2 - genetics / Chemokines / Chromatography / Diabetes / diabetes mellitus / Diet / Donors / Endocrinology and Diabetes / Endokrinologi och diabetes / Energy expenditure / Energy Metabolism / Fatty acids / Fatty Acids, Volatile - analysis / Fecal Microbiota Transplantation / Feces / Feces - chemistry / Gastric Bypass / Gastroenterologi och hepatologi / Gastroenterology and Hepatology / Gastrointestinal Microbiome / Gastrointestinal surgery / Gastrointestinal Transit / Gene Expression / Germfree / Glucose / Glucose - metabolism / Glycerol / Gut Microbiota / Homeostasis / Humans / Inflammation / Insulin / Insulin Resistance / intestinal microbiology / Intestinal microflora / Intestinal transit time / Intestine / Lipolysis / Male / Metabolic syndrome / Metabolic Syndrome - metabolism / Metabolic Syndrome - physiopathology / Metabolic Syndrome - therapy / Metabolites / Metabolomics / Microbiota / Middle Aged / Monocyte chemoattractant protein 1 / Probiotics / Studies / Subcutaneous Fat - metabolism / Surgery / Tissue Donors / Transplantation / Transplants & implants / Weight control / Young Adult