The Effects of Probiotic Supplementation on Anthropometric Growth and Gut Microbiota Composition in Patients With Prader-Willi Syndrome: A Randomized Double-Blinded Placebo-Controlled Trial

Abstract

Background: Prader-Willi Syndrome (PWS) is a rare genetic disorder associated with developmental delay, obesity, and neuropsychiatric comorbidities. Bifidobacterium animalis subsp. lactis has demonstrated anti-obesity and anti-inflammatory effects in previous studies. Aim: To evaluate the effects of Bifidobacterium animalis subsp. lactis probiotics supplementation on anthropometric growth, behavioral symptoms, and gut microbiome composition in patients with PWS. Methods: Ethical Approval was issued by the Internal Review Board (IRB) of the Second Affiliated Hospital of Kunming Medical University (Review-YJ-2016-06). We conducted a 12-week, randomized, double-blind, placebo-controlled trial in 68 patients with Prader-Willi syndrome aged 11 months-16 years (mean = 4.2 years old) who were randomly assigned to receive daily B. lactis-11 probiotics (6 × 10¹⁰ CFUs) or a placebo sachet. Weight, height, ASQ-3, ABC, SRS-2, and CGI-I were compared between the two groups at baseline and at 6 and 12 weeks into treatment. Gut microbiome data were analyzed with the QIIME 2 software package, and functional gene analysis was conducted with PICRUSt-2. Results: We found a significant increase in height (mean difference = 2.68 cm, P < 0.05) and improvement in CGI-I (P < 0.05) in the probiotics group compared to the placebo group. No significant change in weight or psychological measures were observed. Probiotic treatment altered the microbiome composition to favor weight loss and gut health and increased the abundance of antioxidant production-related genes. Conclusions: The findings suggest a novel therapeutic potential for Bifidobacterium animalis subsp. lactis probiotics in Prader-Willi syndrome patients, although further investigation is warranted.

Keywords: Bifidobacterium animalis subsp lactis; Prader-Willi syndrome; height; inflammation; microbiome; microbiota (microorganism); obesity; probiotics.

Figure 1

Flowchart of study conduct and procedure.

Figure 2

Comparison of the height (A–C) and weight (D–F) z-score changes at baseline, from week 0 to 6, and from week 6 to 12 between probiotic groups (blue) and placebo (yellow) using Wilcoxon rank-sum test. As shown in (C), the probiotics group had a significantly greater height (P < 0.05) increase than the placebo group from week 6 to 12.

Figure 3

Comparison of the ABC total score (A), SRS-2 total score (B), ASQ-3 total score (C) and RRB score (D) over the intervention course between probiotics group (blue) and placebo group (brown). There was no group significance found (P > 0.05).

Figure 4

CGI-I of probiotics and placebo at 12 weeks. Percentage of participants given each improvement level was displayed as bar plot, probiotics group (blue) had overall significantly better improvement than the placebo group (yellow, P < 0.05).

Figure 5

Summary of phylum and genus level gut microbiota relative abundances in both probiotics and placebo group subjects at baseline, 6 and 12 weeks. (A) Phylum level gut microbiota relative abundance per group at each study visit. (B) Firmicutes/Bacteroidetes ratio per group at each study visit. (C) Genus level gut microbiota relative abundance per group at each study visit.

Figure 6

α and β diversity index changes from probiotics intervention. (A): observed species index; (B): faith's phylogenetic diversity; (C): Shannon index; (D): Simpson index. *P < 0.05; **P < 0.01, via t-test. (E): β diversity with Non-metric multidimensional scaling (NMDS) score plots of gut microbial data based on a Bray–Curtis dissimilarity matrix. Placebo (red dots) and probiotics (blue dots).

Figure 7

Fold change of relative abundance at genus/species level over the course of intervention for the probiotics group (blue) and placebo (orange). Each bar represents the log 2 transferred relative change of gut microbial abundance of 6 and 12 weeks compared with the baseline. Significant differences are marked with * to indicate P < 0.05.

Figure 8

The predicted KEGG enzyme abundance based on PICRUSt2 functional gene analysis for the probiotics and placebo groups. The average abundance of KEGG enzyme differentially enriched in placebo and probiotics according to level 3.

Figure 9

Correlation between the abundance of bacterial genera and clinical indices using spearman's method was performed for the probiotics (blue) and placebo (yellow) group at the 6-week time point. Probiotic group showed positive correlation between RRB scores and Rothia (R = 0.97, P < 0.005). No significant correlation was observed in the placebo group.