FMT in Obesity: RYGB vs. LEAN vs. Autologous FMT
Status: Recruiting

This double-blinded proof-of-concept study is proposed to explore the effects of fecal microbiota transfer (FMT) in human subjects. Here we perform FMTs into obese recipients using stool from lean unoperated donors and from previously obese patients after successfull treatment with bariatric Roux-en-Y Gastric Bypass (RYGB) surgery. Obese patients treated with their own material (autologous FMT) serve as controls. After FMT treatment the functional impact of post-surgery microbiome changes on host energy consumption and regulation of blood glucose levels will be analysed. Additionally the variations on the microbiota and metabolite composition will be profiled using extensive sequencing analyses. The major aim of the study is to explore the scientific rationale for targeted gut microbiota modulation in management of obesity and related metabolic diseases.We estimate the transfer of microbiota from RYGB donors is superior to the transfer of lean microbiota at inducing reduced adiposity and improving high blood glucose levels in obese recipients. Each is better than a sham procedure (autologous FMT), which itself can also induce considerable short-term effects.

Eligibility:
- EligibilityCriteria: Inclusion Criteria:  - Inclusion criteria for patients  Age >18 years Morbid obesity defined by a BMI ≥ 40 kg/m2 Prediabetes or diabetes with HbA1C between ≥ 5.7 % OR Fasting plasma glucose > 5.6 mmol/l (> 100 mg/dl) (no caloric intake for at least 8 hours) OR Random plasma glucose > 11.1 mmol/l (> 200 mg/dl) Informed consent  Inclusion criteria for RYGB-FMT intervention donors  Sustained total weight loss of ≥30% ≥12 months after RYGB surgery HbA1c < 6.5% without insulin treatment or oral antidiabetic medication Age >18 years Informed consent  Inclusion criteria for LEAN-FMT intervention donors  Normal weight (BMI ≥ 20 to < 25 >18 years Informed consent  Exclusion Criteria:  Exclusion criteria for patients  • Non-Compliance  Insulin dependent diabetes mellitus, treated with GLP-1 agonists or poorly controlled on oral antidiabetic medications (HbA1C > 8%) Use of any weight loss medication or participation in a weight loss program History of recent body weight change (defined as body weight loss or body weight gain of ≥ 5 kg within the two months preceding study enrolment). Use of immunosuppressive medication or immune modulators (glucocorticoids, methotrexate, tacrolimus, cyclosporine, thalidomide, interleukin-10 or -11) within the last three months preceding study enrolment. Congenital or acquired immunodeficiencies. Anatomical reconstruction of the nutrient passage (i.e. hemicolectomy, resection of small bowel, gastrectomy, sleeve gastrectomy, gastric bypass surgery, biliopancreatic diversion, fundoplication etc) or cholecystectomy. Chronic diarrhoea History of serious chronic disease including malignancy, rheumatic heart disease, endocarditis, or valvular disease (due to risk of bacteremia) Any condition, based on clinical judgment that may make study participation unsafe Pregnancy or Breast Feeding  Exclusion criteria for RYGB-FMT intervention donors  Intake of pre-, pro- or antibiotics within < 3 months before study entry Use of immunosuppressive medication or immune modulators (glucocorticoids, methotrexate, tacrolimus, cyclosporine, thalidomide, interleukin-10 or -11) within the last three months preceding study enrolment. Congenital or acquired immunodeficiencies. Chronic or acute infectious diseases (specified under 6.2.1) Drug abuse Anatomical reconstruction of the nutrient passage other than surgical RYGB configuration (i.e. hemicolectomy, resection of small bowel, fundoplication, LSG-to-RYGB transformation etc) or cholecystectomy. History of recent body weight change (defined as body weight loss or body weight gain of ≥ 5 kg within the two months preceding study enrolment). Chronic diarrhoea or steatorrhea or acute gastrointestinal infection within ≤ 3 months before study entry. History of serious chronic disease including malignancy, chronic kidney disease (eGFR < 60 ml/min), heart failure (NYHA ≥ III). Any further condition, based on clinical judgment that may disqualify the candidate as an appropriate donor.  Exclusion Criteria for Lean-FMT Intervention Donors • History of overweight or obesity in the past (BMI > 25 kg/m2)  • History of recent body weight change (defined as body weight loss or body weight gain of ≥ 5 kg within the two months preceding study enrolment).  • HbA1C > 6.5% or treatment with insulin or oral anti-diabetic medication.  • Use of any weight loss medication or participation in a weight loss program  • Use of immunosuppressive medication or immune modulators (glucocorticoids, methotrexate, tacrolimus, cyclosporine, thalidomide, interleukin-10 or -11) within the last three months preceding study enrolment.  • Congenital or acquired immunodeficiencies.  • Chronic or acute infectious diseases (specified under 6.2.1)  • Drug abuse  • Anatomical reconstruction of the nutrient passage (i.e. hemicolectomy, resection of small bowel, fundoplication etc) or cholecystectomy.  • Chronic diarrhoea or acute gastrointestinal infection within ≤ 3 months before study entry.  • History of serious chronic disease including malignancy, chronic kidney disease (eGFR < 60 ml/min), heart failure (NYHA ≥ III).  • Any further condition, based on clinical judgment that may disqualify the candidate as an appropriate donor. - HealthyVolunteers: Accepts Healthy Volunteers - Gender: All - MinimumAge: 18 Years - MaximumAge: 60 Years - StdAgeList: Adult