Clinical efficacy of weight loss herbal intervention therapy and lifestyle modifications on obesity and its association with distinct gut microbiome: A randomized double-blind phase 2 study

Abstract

Goals: To assess the efficacy and safety of Chinese Medicine Prescription "W-LHIT" in subjects with simple obesity, and to explore its potential mechanism of action.

Methods: Thirty-seven patients aged 18 to 60 from Wei-En hospital (Weifang City, Shandong, China), participated in a double blinded, placebo-controlled study. Subjects were randomly divided into 2 groups, 18 in treatment and 19 in placebo group. The treatment group took the "W-LHIT" capsules for two months, while the control group received placebo capsules. Both groups accepted healthy lifestyle education materials. After a 2-month treatment, the placebo group transferred to open-label treatment after unblinding.

Results: 72.22% participants in the treatment group lost more than 5% of their body weight, compared with 36.84% in the placebo group (p < 0.001). Body weight loss and body mass index reduction of the treatment group were also significantly higher than those of the placebo group (p < 0.05). These changes were accompanied by increased abundance of Akkermansia muciniphila and Enterococcus faecium, and decreased abundance of Proteobacteria in gut microbiota. Furthermore, the treatment group also showed improvement in obesity-related comorbidities such as hypertension and elevation of liver enzymes. No serious adverse reactions were found during the study period. Weight did not rebound at a follow-up visit 2 months after treatment.

Conclusion: W-LHIT significantly improved body weight and comorbid conditions without obvious adverse reaction or rebound weight gain. These effects were associated with increased abundance of probiotics in gut microbiota. W-LHIT may have a potential for treating obesity in conjunction with healthy lifestyle modifications.

Keywords: Akkermansia muciniphila; gut microbiome; lifestyle modifications; obesity; weight loss; “W-LHIT” capsule.

Figure 1

The Reduction in body weight (A), BMI (B), hip circumference (C), waist circumference (D). The reduction in body weight was significantly greater in the treatment group than in the placebo group after 2 months (2M). Bars were shown as mean of each group. All intra-group analysis were performed by using one-way ANOVA followed by bonferroni post hoc, and all inter-group analysis for baseline and treatment effects were performed by using t test followed by Mann-Whitney (# represents p < 0.05) by Prism 9 software (*, ** and *** represent p < 0.05, p < 0.01 and p < 0.001). Body mass index, BMI.

Figure 2

Mean Changes in SDBP (A), SSBP (B), HR (C) and Blood sugar levels (D). The reduction in SDBP was significantly greater in the treatment group than in the placebo group after 2 months (2M). Bars (blue) were shown as mean of each group with 95% CI. All intra-group analyses were performed using one-way ANOVA followed by Bonferroni post hoc, and inter-group was performed by using t test followed by Mann-Whitney by Prism 9 software, (*, ** and *** represent p < 0.05, p < 0.01 and p < 0.001; # represents p < 0.05, ns represents no significant difference). Seated systolic blood pressure, SSBP, seated diastolic blood pressure, SDBP, mmHg.

Figure 3

W-LHIT significantly reduced total cholesterol (TC), blood triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C). (A) TC; (B) TG; (C) LDL-C; (D) HDL-C. Bars were shown as mean of each group with 95% CI. All intra-group analyses were performed using one-way ANOVA followed by Bonferroni post hoc, and inter-group was performed by using t test followed by Mann-Whitney by Prism 9 software (*, ** and *** represent p < 0.05, p < 0.01, p < 0.001, ns represents no significant difference). TC, Total cholesterol; TG, triglycerides; LDL-C, low-density lipoprotein; and HDL-C, high-density lipoprotein cholesterol.

Figure 4

Hs-CRP level was significantly reduced after the treatment. Bars were shown as mean of each group with 95% CI. Intra-group analyses were performed using one-way ANOVA followed by Bonferroni post hoc, inter-group analyses were performed by using t test followed by Mann-Whitney by Prism 9 software (** and *** represent p < 0.01 and p < 0.001). Hs-CRP, High-sensitivity C-reactive protein.

Figure 5

Weight did not rebound in the treatment group at a follow-up visit 2 months after the treatment. Bars were shown as mean of each group. The analyses were performed using one-way ANOVA followed by Bonferroni post hoc by Prism 9 software.

Figure 6

(A) Rank abundance curve. Each curve represents a group; placebo group (WLCB (baseline), WLCA (post treatment)) and treatment group (WLTB (baseline) and WLTA (post treatment)). (B) PLS-DA plots based on unweighted unifrac metrics. Each symbol represents a sample from the placebo group or treatment group, respectively.

Figure 7

The structures and compositions of the gut microbiota before and after treatment in the two groups. (A) The Venn diagram of OTUs (species). (B) The composition of relative abundance on genus. (C) Phylogenetic cladogram of microbial lineage in fecal samples of treatment group and placebo group, with colors representing the most abundant differences in composition. (D) Key phylotypes of the gut microbiota responding to W-LHIT treatment. The histogram shows the lineage with LDA value of 4 or higher determined by LEFSe. (E) Key KEGG metabolic pathway responding to W-LHIT treatment.