Objective The impact of faecal microbiota transplantation (FMT) on microbiota engraftment in patients with metabolic syndrome is uncertain. We aimed to study whether combining FMT with lifestyle modification could enhance the engraftment of favourable microbiota in obese patients with type 2 diabetes mellitus (T2DM).
Design In this double-blind, randomised, placebo-controlled trial, 61 obese subjects with T2DM were randomly assigned to three parallel groups: FMT plus lifestyle intervention (LSI), FMT alone, or sham transplantation plus LSI every 4 weeks for up to week 12. FMT solution was prepared from six healthy lean donors. Faecal metagenomic sequencing was performed at baseline, weeks 4, 16 and 24. The primary outcome was the proportion of subjects acquiring ≥20% of microbiota from lean donors at week 24.
Results Proportions of subjects acquiring ≥20% of lean-associated microbiota at week 24 were 100%, 88.2% and 22% in the FMT plus LSI, FMT alone, and sham plus LSI groups, respectively (p<0.0001). Repeated FMTs significantly increased the engraftment of lean-associated microbiota (p<0.05). FMT with or without LSI increased butyrate-producing bacteria. Combining LSI and FMT led to increase in Bifidobacterium and Lactobacillus compared with FMT alone (p<0.05). FMT plus LSI group had reduced total and low-density lipoprotein cholesterol and liver stiffness at week 24 compared with baseline (p<0.05).
Conclusion Repeated FMTs enhance the level and duration of microbiota engraftment in obese patients with T2DM. Combining lifestyle intervention with FMT led to more favourable changes in recipients’ microbiota and improvement in lipid profile and liver stiffness.
Trial registration number NCT03127696.
- enteric bacterial microflora
Data availability statement
Sequencing data were uploaded to NCBI under Bioproject PRJNA644456. Data are available on reasonable request.
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SCN and ZX contributed equally.
Contributors SCN and FKLC contributed to the study design, direction, guidance and manuscript writing; ZX and KY performed microbiome analysis and drafting of manuscript; JWYM and AYLL contributed to analysis of clinical data and manuscript preparation; CHH performed lifestyle intervention; TZ, QL, PC and WT contributed to study design; YKT provided statistical input and analysis; VW-SW performed fibroscan; SW, AP-SK, RM, EC, KC and JYLC contributed to subject recruitment, sample collection and processing; SKHW, LL and RNL performed FMT/sham infusion procedures.
Funding This study was funded by InnoHK, The Government of Hong Kong, Special Administrative Region of the People’s Republic of China; seed fund from Centre for Gut Microbiota Research, Faculty of Medicine, The Chinese University of Hong Kong.
Disclaimer The funder of the study had no role in study design, data collection, data analysis, data interpretation, or writing report.
Competing interests SCN has served as advisory board member for Pfizer, Ferring, Janssen, Abbvie and speaker for Ferring, Tillotts, Menarini, Janssen, Abbvie and Takeda. She has received research grants from Olympus, Ferring and Abbvie. FKLC has served as advisor and Lecture Speaker for Eisai Co. Ltd, AstraZeneca, Pfizer Inc, Takeda Pharmaceutical Co and Takeda (China) Holdings Co. Ltd. VW-SW has served as a consultant or advisory board member for 3V-BIO, AbbVie, Allergan, Boehringer Ingelheim, Center for Outcomes Research in Liver Diseases, Echosens, Gilead Sciences, Hanmi Pharmaceutical, Intercept, Merck, Novartis, Novo Nordisk, Perspectum Diagnostics, Pfizer, ProSciento, Sagimet Biosciences, TARGET PharmaSolutions and Terns; and a speaker for AbbVie, Bristol-Myers Squibb, Echosens and Gilead Sciences. He has received a grant from Gilead Sciences for fatty liver research. ZX: none to declare. JWYM: none to declare. KY: none to declare. QL: none to declare. TZ: none to declare. WT: none to declare. LL: none to declare. RNL: none to declare. SW: none to declare. YKT: none to declare. AYLL: none to declare. KC: none to declare. JYLC: none to declare. AP-SK: none to declare. RM: none to declare. EC: none to declare. SKHW: none to declare. CHH: none to declare. PC: none to declare.
Provenance and peer review Not commissioned; externally peer reviewed.
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