Periodic Reporting for period 1 - Microbes4U (Study of the therapeutic potential of an Akkermansia muciniphila-based products in subjects with an increased cardio-metabolic risk.)
Reporting period: 2016-07-01 to 2017-12-31
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). All these metabolic features represent a major public health problem. Therefore, it is urgent to find solutions to target all these metabolic disorders. Among the environmental factors influencing the individual susceptibility to develop metabolic disorders associated with obesity, we have contributed to the demonstration that gut bacteria (i.e gut microbiota) influence host metabolism.
We discovered that the bacterium "Akkermansia muciniphila" is an excellent candidate. Indeed, the administration of Akkermansia muciniphila reduced body weight gain, fat mass gain, glycemia, cholesterolemia and inflammatory markers in diet-induced obese mice (Everard et al PNAS 2013). Moreover, we discovered that in overweight/obese subjected elected for a calorie restriction diet, the higher abundance of Akkermansia muciniphila was associated with a better cardio-metabolic status. 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 have investigated the safety and the beneficial effects of Akkermansia muciniphila administration on obesity and metabolic disorders.
Thus, the main objective of this ERC POC project “Microbes4U” was first to produce the bacteria in conditions suitable for human use and then to test in humans its safety.
For that purpose, we conducted a single blind, placebo-controlled, randomized study with 4 groups of 10 to 12 volunteers per group. The volunteers were selected according to strict and specific inclusion/exclusion criteria that is for example having a metabolic syndrome with cardio-metabolic risk factors and no specific medications (www.microbes4U.be).
In summary, the volunteers received a daily dose of Live Akkermansia muciniphila (10exp9 cfu/day) or Live Akkermansia muciniphila (10exp10 cfu/day) or Pasteurized Akkermansia muciniphila (10exp10 cells/day) or a Placebo (PBS/Glycerol) during a period of 3 months. Different biological samples (blood, urine, fecal material) have been kept for analysis. A first safety check (liver enzymes, kidney functions, muscles enzymes, inflammation, immunity and tolerance) has been performed after 15 days and a second after 3 months of daily administration of the bacteria (or placebo).
The data clearly show that the ingestion of Akkermansia muciniphila either live or pasteurized at a dose of up to 10 Billion cells per day for a period of 3 months was well tolerated and safe for the volunteers. After the end of the study (i.e. 20/02/18) we will start the analysis of metabolic and other biological parameters.
In conclusion, the pilot study Microbes4U has led to the first demonstration that the administration of the bacterium Akkermansia muciniphila is feasible and safe in human volunteers. It is worth noting that further analysis will be done on the samples obtained during this first pilot study. One part of the results have been published in Plovier et al Nature Medicine 2017 (https://www.nature.com/articles/nm.4236(opens in new window))
We discovered that the bacterium "Akkermansia muciniphila" is an excellent candidate. Indeed, the administration of Akkermansia muciniphila reduced body weight gain, fat mass gain, glycemia, cholesterolemia and inflammatory markers in diet-induced obese mice (Everard et al PNAS 2013). Moreover, we discovered that in overweight/obese subjected elected for a calorie restriction diet, the higher abundance of Akkermansia muciniphila was associated with a better cardio-metabolic status. 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 have investigated the safety and the beneficial effects of Akkermansia muciniphila administration on obesity and metabolic disorders.
Thus, the main objective of this ERC POC project “Microbes4U” was first to produce the bacteria in conditions suitable for human use and then to test in humans its safety.
For that purpose, we conducted a single blind, placebo-controlled, randomized study with 4 groups of 10 to 12 volunteers per group. The volunteers were selected according to strict and specific inclusion/exclusion criteria that is for example having a metabolic syndrome with cardio-metabolic risk factors and no specific medications (www.microbes4U.be).
In summary, the volunteers received a daily dose of Live Akkermansia muciniphila (10exp9 cfu/day) or Live Akkermansia muciniphila (10exp10 cfu/day) or Pasteurized Akkermansia muciniphila (10exp10 cells/day) or a Placebo (PBS/Glycerol) during a period of 3 months. Different biological samples (blood, urine, fecal material) have been kept for analysis. A first safety check (liver enzymes, kidney functions, muscles enzymes, inflammation, immunity and tolerance) has been performed after 15 days and a second after 3 months of daily administration of the bacteria (or placebo).
The data clearly show that the ingestion of Akkermansia muciniphila either live or pasteurized at a dose of up to 10 Billion cells per day for a period of 3 months was well tolerated and safe for the volunteers. After the end of the study (i.e. 20/02/18) we will start the analysis of metabolic and other biological parameters.
In conclusion, the pilot study Microbes4U has led to the first demonstration that the administration of the bacterium Akkermansia muciniphila is feasible and safe in human volunteers. It is worth noting that further analysis will be done on the samples obtained during this first pilot study. One part of the results have been published in Plovier et al Nature Medicine 2017 (https://www.nature.com/articles/nm.4236(opens in new window))