Effects of Bifidobacterium animalis Subsp. lactis (BPL1) Supplementation in Children and Adolescents with Prader–Willi Syndrome: A Randomized Crossover Trial

Abstract

Prader–Willi syndrome (PWS) is a rare genetic disorder characterized by a wide range of clinical manifestations, including obesity, hyperphagia, and behavioral problems. Bifidobacterium animalis subsp. lactis strain BPL1 has been shown to improve central adiposity in adults with simple obesity. To evaluate BPL1′s effects in children with PWS, we performed a randomized crossover trial among 39 patients (mean age 10.4 years). Participants were randomized to placebo–BPL1 (n = 19) or BPL1–placebo (n = 20) sequences and underwent a 12-week period with placebo/BPL1 treatments, a 12-week washout period, and a 12-week period with the crossover treatment. Thirty-five subjects completed the study. The main outcome was changes in adiposity, measured by dual-energy X-ray absorptiometry. Secondary outcomes included lipid and glucose metabolism, hyperphagia, and mental health symptoms. Generalized linear modeling was applied to assess differences between treatments. While BPL1 did not modify total fat mass compared to placebo, BPL1 decreased abdominal adiposity in a subgroup of patients older than 4.5 years (n = 28). BPL1 improved fasting insulin concentration and insulin sensitivity. Furthermore, we observed modest improvements in some mental health symptoms. A follow-up trial with a longer treatment period is warranted to determine whether BPL1 supplementation can provide a long-term therapeutic approach for children with PWS (ClinicalTrials.gov NCT03548480).

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

“…This non-significant trend provides additional evidence in support of the findings by Amat-Bou et al that Lact. reuteri improves insulin signaling and, in this way, promotes normal weight [15]. However, while the probiotic study conducted by Amat-Bou et al demonstrated such positive effects in individuals with PWS using the Bifidobacterium strain BPL1, it is unsurprising that such effects are also observed in the present study of LR-99, as both Bifidobacteria and Lactobacilli have important interconnected functional roles in the gut such as fructose and oligosaccharide metabolism [52].…”

“…One recent study found that Lact. reuteri administration in the PWS population improved insulin sensitivity and decreased abdominal adiposity in children older than 4.5 years of age [15]. However, the mechanisms involved in the induction of such effects remain unclear and may manifest in many different bacteria.…”

“…Notably, a recent study found that Lact. reuteri administration in the PWS population improved fasting insulin concentration and insulin sensitivity and decreased abdominal adiposity in children older than 4.5 years of age [15]. Lactobacillus reuteri has also been shown to exert beneficial effects on the brain and behavior [16].…”

Targeting the Gut Microbiome in Prader-Willi Syndrome

“…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].…”