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.

Targeting the Gut Microbiome in Prader-Willi Syndrome

“…Notably, improvements in social behavior induced by this probiotic had been previously reported in a mouse model of autism spectrum disorder [48]. β-diversity showed a significant separation with probiotic treatment compared to placebo, as also reported in the study with B. lactis [33]. Furthermore, the authors also described probioticinduced changes in the gut microbiota that could contribute to the beneficial effects of the intervention, including lower Escherichia-Shigella and higher Bifidobacterium, Lactobacillus, Faecalibacterium, and Roseburia abundance.…”

“…For this purpose, a literature review up until July 2021 was carried out using PubMed database searches with the following terms: "Prader-Willi syndrome" and "gut/intestinal microbiome/microbiota". We identified 13 publications that included both observational [25][26][27][28] and interventional studies [29][30][31][32][33], a study protocol [34], and three studies based on secondary analyses of microbiome data from previously published articles [35][36][37]. Publications were classified based on their evidence level in accordance with the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology, considering the lowest evidence level "Expert opinion" (score 4) and the highest evidence level "High quality meta-analysis, systematic reviews of randomized controlled trials (RCTs), or RCTs with a very low risk of a bias" (score 1 ++ ) [38].…”

“…To this date, four randomized controlled clinical studies have evaluated the effects of probiotic supplementation in individuals with PWS using two different bacterial species, namely B. lactis and L. reuteri without significant adverse events (Table 2) [30][31][32][33]. Additionally, a study implementing a dietary intervention with prebiotics and a fiber-rich diet has also been reported [29].…”

“…Recently, a larger clinical trial designed to test two different probiotic strains in a crossover fashion has been completed; results were independently evaluated for each bacterial strain and reported in two different publications as parallel-group clinical studies [32,33]. First, the authors conducted a randomized, double-blind, placebo-controlled 12-week trial to evaluate the efficacy of B. lactis (BL-11) on weight, height, and psychological measurements [33]. Sixty-eight subjects with PWS aged 4.2 ± 3.1 years were analyzed.…”

The Effects of Limosilactobacillus reuteri LR-99 Supplementation on Body Mass Index, Social Communication, Fine Motor Function, and Gut Microbiome Composition in Individuals with Prader–Willi Syndrome: a Randomized Double-Blinded Placebo-Controlled Trial

“…The evaluation of effects of the alternative probiotic strain Bifidobacterium Animalis subsp. lactis BB-11, which was co-registered with the present study, was previously published [21]. Signed informed consent was obtained from the parents or legal guardians of all the subjects according to the IRB requirements.…”