The Probiotic Strain H. alvei HA4597® Improves Weight Loss in Overweight Subjects under Moderate Hypocaloric Diet: A Proof-of-Concept, Multicenter Randomized, Double-Blind Placebo-Controlled Study

Pierre Déchelotte, Jonathan Breton, Clémentine Trotin-Picolo, Barbara Grube, Constantin Erlenbeck, Gordana Bothe, Sergueï O Fetissov, Grégory Lambert, Pierre Déchelotte, Jonathan Breton, Clémentine Trotin-Picolo, Barbara Grube, Constantin Erlenbeck, Gordana Bothe, Sergueï O Fetissov, Grégory Lambert

Abstract

Background: Increasing evidence supports the role of the gut microbiota in the control of body weight and feeding behavior. Moreover, recent studies have reported that the probiotic strain Hafnia alvei HA4597® (HA), which produces the satietogenic peptide ClpB mimicking the effect of alpha-MSH, reduced weight gain and adiposity in rodent models of obesity. Methods: To investigate the clinical efficacy of HA, 236 overweight subjects were included, after written informed consent, in a 12-week prospective, double-blind, randomized study. All subjects received standardized counselling for a -20% hypocaloric diet and were asked to maintain their usual physical activity. Subjects of the HA group received two capsules per day providing 100 billion bacteria per day and subjects in the Placebo (P) group received two placebo capsules. The primary endpoint was the percentage of subjects achieving a weight loss of at least 3% after 12 weeks. Intention-to-treat statistical analysis was performed using exact-Fischer, Mann-Whitney and paired-Wilcoxon tests as appropriate. Results: In the HA group, significantly more subjects (+33%) met the primary endpoint than in the P group (54.9 vs. 41.4%, p = 0.048). In the HA group, an increased feeling of fullness (p = 0.009) and a greater loss of hip circumference (p < 0.001) at 12 weeks were also observed. Fasting glycemia at 12 weeks was significantly lower (p < 0.05) in the HA compared to P group. Clinical and biological tolerance was good in both groups. Conclusions: A 12-week treatment with the probiotic strain H. alvei HA4597® significantly improves weight loss, feeling of fullness and reduction of hip circumference in overweight subjects following moderate hypocaloric diet. These data support the use of H. alvei HA4597® in the global management of excess weight.

Keywords: H. alvei HA4597; HA4597®; appetite; feeling of fullness; gut microbiota; hip circumference; overweight subjects; probiotics.

Conflict of interest statement

S.O.F., J.B., P.D. and G.L. are inventors of patents supporting the technology used in the study. S.O.F. and P.D. are founders, shareholders and consultants of TargEDys SA. C.E. is a former and G.B. a current employee of Analyze & Realize. B.G. is an MD at a practice for general medicine in Berlin. C.T.-P. and G.L. are employees of TargEDys.

Figures

Figure 1
Figure 1
Flowchart illustrating the steps of screening, enrollment, assignment and follow-up of study participants for the Intent To Treat (ITT) and Per Protocol (PP) analysis.
Figure 2
Figure 2
Effect of HA supplementation on the proportion of responders losing at least 3% of body weight. Proportion of overweight subjects losing at least 3% of body weight in ITT (A) and PP (B) populations. (A,B) Exact Fisher’s test P. vs. HA.* p ≤ 0.05.
Figure 3
Figure 3
Proportion of responders losing at least 4% of body weight after 12 HA supplementation. Proportion of HA treated subjects losing at least 4% of body weight in ITT (A) and PP (B) populations. Exact Fisher’s test P. vs. HA.* p ≤ 0.05.
Figure 4
Figure 4
Changes in hip circumference following 12 weeks of HA supplementation in overweight subjects. Changes in Hip circumference following 12 weeks of HA supplementation compared to week 0 in ITT (A) and PP (B) population. (A,B) Mann-Whitney-U test (w12-w0)P. vs. (w12-w0)HA.*** pU ≤ 0.001.
Figure 5
Figure 5
Feeling of fullness in overweight subject treated with HA under hypocaloric diet. Feeling of fullness in ITT (A) and PP (B) populations. Changes in the feeling of fullness over 12 weeks of HA supplementation in ITT (C) and PP (D) population. (A,B) Mann-Whitney-U test (w12)P. vs. (w12)HA.** pU ≤ 0.01.*pU ≤ 0.05. (C) Mann-Whitney-U test; (w12-w0)P. vs. (w12-w0)HA.* pU ≤ 0.05. Paired Wilcoxon test; HA(w0) vs. HA(w12).** pwi ≤ 0.01 (D) Mann-Whitney-U test; (w12-w0)P. vs. (w12-w0)HA.* pU ≤ 0.05. Paired Wilcoxon test; HA(w0) vs. HA(w12).* pwi ≤ 0.05.
Figure 6
Figure 6
Global assessment of the treatment by the blinded subjects and investigators in the HA and P groups.

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