Evaluation of the Effects Associated With the Administration of Akkermansia Muciniphila on Parameters of Metabolic Syndrome
Evaluation of the Effects Associated With the Administration of Akkermansia Muciniphila on Parameters of Metabolic Syndrome
Overweight and obesity have reached worldwide epidemic level. Both overweight and obesity are
 characterized by comorbidities such as cardio-metabolic risk factors (i.e., insulin
 resistance, type 2 diabetes, hypertension, dyslipidemia, low-grade inflammation) representing
 a major public health problem. Therefore, it is urgent to find a therapeutic solution to
 target all these metabolic disorders. Among the environmental factors able to influence the
 individual susceptibility to gain weight and to develop metabolic disorders associated with
 obesity, more and more evidence show that the trillions of bacteria housed in our
 gastro-intestinal tract (i.e, gut microbiota) influence host metabolism. The investigators
 recently discovered a putative interesting microbial candidate, namely Akkermansia
 muciniphila (Akk). More exactly, we found that the administration of Akkermansia muciniphila
 reduced body weight gain, fat mass gain, glycemia and inflammatory markers in diet-induced
 obese mice. Moreover, in overweight/obese patients with cardiovascular risk factors subjected
 to a calorie restriction diet (calorie restriction diet for 6 weeks and an additional 6 weeks
 of weight maintenance), a higher abundance of Akkermansia muciniphila was associated with a
 better cardio-metabolic status in these patients. The investigators also discovered that
 patients having more Akkermansia muciniphila in their gut before the calorie restriction
 exhibited a greater improvement in glucose homoeostasis, blood lipids and body composition
 after calorie restriction. These observations suggested that the administration of
 Akkermansia muciniphila in overweight or obese people could be a very interesting therapeutic
 solution. Currently, no human study has investigated the beneficial effects of Akkermansia
 muciniphila administration on obesity and metabolic disorders. The overall objective of this
 study is to evaluate the effects associated with the administration of live or heat-killed
 Akkermansia muciniphila on the metabolic disorders (insulin-resistance, type-2 diabetes,
 dyslipidemia, inflammation) related to overweight and obesity in humans.
Inclusion Criteria:

 -  Aged between 18 and 70 years old

 -  Caucasian

 -  Insulin resistance (based on HOMA single-value)

 -  BMI between 25 and 50 kg/m²

 -  Metabolic syndrome: presence of at least 3 of the following criteria

 -  Hypertension (blood pressure ≥ 130/85 mm Hg or antihypertensive treatment)

 -  Hypertriglyceridemia (triglyceridemia ≥ 150mg/dl)

 -  Low HDL-cholesterol (HDL-cholesterol < 40mg/dl for males, 50mg/dl for females)

 -  Visceral obesity (waist circumference > 102 cm for males, 88cm for females)

 -  Fasting hyperglycemia (fasting glycemia ≥ 110mg/dl)

 -  Informed consent signed by the patient

 Exclusion Criteria:

 -  Acute or chronic progressive or chronic unstabilized diseases

 -  Alcohol consumption (more than 2 glasses per day)

 -  Previous bariatric surgery

 -  Surgery in the 3 months prior the study or surgery planned in the next 6 months

 -  Pregnancy or pregnancy planned in the next 6 months

 -  More than 30 minutes of sports 3 times per week

 -  Consumption of dietary supplement (omega-3 fatty acids, probiotics, prebiotics, plant
 stanols/sterols) in the month prior the study

 -  Inflammatory bowel disease or irritable bowel syndrome

 -  Diabetic gastrointestinal autonomic neuropathy (such as gastroparesis or reduced
 gastrointestinal motility)

 -  Consumption of more than 30g of dietary fibers per day

 -  Vegetarian or unusual diet

 -  Lactose intolerance or milk protein allergy

 -  Gluten intolerance

 -  Medications influencing parameters of interest (antidiabetic drugs such as metformin,
 DPP-4 inhibitors, GLP-1 receptor agonists, acarbose, hypoglycemic
 sulfonamides,glinides, thiazolidinediones, SGLT2 inhibitors, insulin,lactulose,
 consumption of antibiotics in the 2 months prior the study, corticosteroids,
 immunosuppressive agents, statins, fibrate, orlistat, cholestyramine, ezetimibe)

 -  Glycated hemoglobin (HbA1c) > 7.5%