Lachnospiraceae in the gut microbiota and association with body weight

Abstract

The present invention relates to means and methods for modulating the gut microbiota composition of a subject, preferably a human. In particular, the present invention provides an agent capable of reducing the proportion of Lachnospiraceae in the gut microbiota composition of a subject which agent is useful for promoting weight loss or preventing weight gain in a subject, preferably an obese or overweight subject. Lactobacillus rhamnosus CGMCC 1.3724 is particularly preferred as the agent provided by and used in the present invention.

Claims

1. A method for promoting weight loss or preventing weight gain in an obese or overweight subject having low responsiveness to a calorie restricted diet, the low responsiveness dependent on gut microbiota composition of the obese or overweight subject, the gut microbiota composition of the obese or overweight subject who has low responsiveness to the calorie restricted diet comprises a higher proportion of Lachnospiraceae relative to that of a normal weight subject, the method comprising the step of administering an agent comprising a probiotic comprising Lactobacillus rhamnosus CGMCC 1.3724 to the subject.

2. The method according to claim 1, wherein the agent is administered during, subsequent to and/or prior to the calorie restricted diet, in an amount therapeutically effective for promoting weight loss in the obese or overweight subject having low responsiveness to the calorie restricted diet.

3. The method according to claim 1, wherein the agent is administered subsequent to the calorie restricted diet, in an amount therapeutically effective for preventing weight gain in the obese or overweight subject having low responsiveness to the calorie restricted diet.

4. The method according to claim 1, wherein the calorie restricted diet is a dietary regimen for at least twelve weeks, and the agent is administered during the calorie restricted diet and also during a subsequent period without calorie restriction for at least twelve additional weeks.

5. The method according to claim 1, wherein the weight loss involves a body fat loss, or the weight gain involves a body fat gain.

6. The method according to claim 1, wherein the Lactobacillus rhamnosus CGMCC 1.3724 is administered to the subject at a daily dosage in the range of 10.sup.2 to 10.sup.12 cfu.

7. The method according to claim 1, wherein the agent is administered to the subject during, subsequent to and/or prior to the calorie restricted diet, the calorie restricted diet involves a reduction of the daily calorie intake in the range of 200 to 1000 kcal.

8. The method according to claim 1, wherein the proportion of Lachnospiraceae in the gut microbiota composition of the obese or overweight subject who has the low responsiveness to the calorie restricted diet exceeds that of a normal weight subject by at least 5%.

9. The method according to claim 1, wherein the proportion of Lachnospiraceae in the gut microbiota composition of the obese or overweight subject who has the low responsiveness to the calorie restricted diet exceeds that of a normal weight subject by at least 10%.

10. The method according to claim 1, wherein the proportion of Lachnospiraceae in the gut microbiota composition of the obese or overweight subject who has the low responsiveness to the calorie restricted diet exceeds that of a normal weight subject by at least 15%.

11. The method according to claim 1, wherein the agent is administered to the subject for a period of time of greater than 12 weeks.

Description

(1) Further advantages and features of the present invention will be apparent to those of skill in the art from the following examples and figures.

BRIEF DESCRIPTION OF THE FIGURES

(2) FIG. 1 shows the development of the relative abundance (%) of Lachnospiraceae family in women at week 0, week 12 and week 24 in the placebo (white circle) or the probiotic group (black circle). Data represent medianSE median. Values statistically different from placebo are indicated as **: p<0.01.

(3) FIG. 2 shows the relative abundance (%) of Lachnospiraceae family in lean and obese subjects. Data represent medianSE median. The difference is statistically significant at p=0.03

(4) FIG. 3 shows weight and fat mass loss at 12 weeks and 24 weeks, in the placebo or probiotic group, in the placebo or probiotic group, It also shows that weight loss is essentially due to fat mass loss.

EXAMPLES

Example 1

Lactobacillus rhamnosus CGMCC 1.3724 Promotes Body Weight Loss and Reduces the Proportion of Lachnospiraceae in Gut Microbiota Composition

(5) The effects of Lactobacillus rhamnosus CGMCC 1.3724 consumption on body weight and gut microbiota composition were tested in healthy adult volunteers (women).

(6) During the double blind, placebo-controlled, randomized trial each subject consumed 2 capsules per day of either a placebo (310 mg of maltodextrin) or a probiotic formulation (10 mg of (Lactobacillus rhamnosus CGMCC 1.3724; 1.6 10.sup.8 cfu/capsule, 210 mg of oligofructose and 90 mg of inulin). Both groups were submitted to a moderate energy restriction (500 kcal/day) for the first 12 weeks (weight loss period) followed by 12 weeks of weight maintenance. Body weight and gut microbiota composition (pyrosequencing of 16S RNAs) were measured at baseline, 12 and 24 weeks. After the first 12 weeks, mean weight loss for women in the probiotic group was significantly higher than for those in the placebo group (4.43.0 vs 2.62.3 kg; p=0.02, respectively), and this effect was sustained after the weight maintenance period (2.53.5 vs 5.24.0 kg; p=0.02, respectively). This is shown in FIG. 3

(7) Furthermore, gut microbiota composition analysis revealed a significant decrease in Lachnospiraceae proportion (by 15% when compared with baseline level) associated with weight loss in women consuming the probiotic formulation (FIG. 1).

(8) It was thus concluded that consumption of Lactobacillus rhamnosus CGMCC 1.3724 supports weight loss, in particular when consumed during a moderate calorie restricted diet, and that said weight loss is associated with reduction in Lachnospiraceae proportion in gut microbiota.

Example 2

Lachnospiraceae Proportion in Gut Microbiota Composition is Related to Body Weight and Obesity

(9) Fecal samples were collected from two groups of adult individuals: 20 lean non diabetic subjects (BMI: 22.3+/1.8 kg/cm.sup.2) and 25 obese non diabetic subjects (BMI: 31.5+/4.8 kg/cm.sup.2) who both followed balanced typical Western diets 14 days before fecal collection. Subjects were matched by gender and ethnic background in both groups. Fecal microbiota composition was measured by pyrosequencing of variable regions (V1 and V2) of the 16S RNA genes present in the microbial population. We showed a significantly higher proportion of Lachnospiraceae (+7%) associated with the group of obese subjects (FIG. 2).

(10) It was thus concluded that obesity in humans is associated with a higher abundance of fecal Lachnospiraceae.