Microbiome modulation and behavioural improvements in children with fragile X syndrome following probiotic intake - A pilot study

Sep 30, 2026

The gut microbiome-gut-brain axis is investigated in fragile X syndrome (FXS), where the microbial contribution remains largely unclear. In an open-label single-arm pilot study, 15 children with genetically confirmed FXS received a daily probiotic mixture containing Lactobacillus casei, Lactobacillus salivarius, and Bifidobacterium breve for 12 weeks. Behavioral assessments and metagenomic analyses with network and pathway methods were conducted before and after supplementation. Irritability, communication, socialization, and adaptive behavior improved significantly, alongside increased microbial connectivity measures and pathway trends. Results suggest probiotics may modulate GM structure and function with potential links to better behavioral outcomes.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages13

Reading Time33 min

AccessFree to download

Study overview

Participants and probiotic intervention

Behavioral outcomes and metagenomic methods

Network and functional pathway findings

Conclusions and future directions

[www. nature.com/scientificreports](www. nature.com/scientificreports) OPEN Microbiome modulation and behavioural improvements in children with fragile X syndrome following probiotic intake: A pilot study Dragana Protic1,2􀀍, Danijela Bascarevic2, Sanja Dimitrijevic3, Jovan Pesovic4, Vladimir Nikolic5, Sasa Nikolic2, Velibor Novicevic2, Jovana Markovic2, Irena Arandjelovic6, Dusanka Savic-Pavicevic4, Margo Diricks7,8,10, Meriem Belheouane9 & Matthias Merker9,10􀀍 The gut microbiome (GM) is increasingly recognized as a key modulator of neurodevelopment via the microbiome-gut-brain axis. Fragile X syndrome (FXS), the most common inherited monogenic cause of intellectual disability, shares behavioural and molecular features with other neurodevelopmental disorders (NDDs), yet the role of the GM in FXS remains largely unexplored. In this open-label, singlearm trial, 15 children with genetically confirmed FXS received a daily probiotic formulation containing Lactobacillus casei, Lactobacillus salivarius, and Bifidobacterium breve for 12 weeks. Behavioural analysis and metagenomic sequencing with network and pathway analyses were performed before and after probiotic supplementation. Significant improvements were observed in irritability (-3.9, SD: ± 5.2; p = 0.027), communication (+ 1.7, SD: ± 2.5; p = 0.022), socialization (+ 1.4, SD: ± 2.1; p = 0.033), and adaptive behaviour (+ 1.3, SD: ± 1.4; p = 0.004). While overall microbial diversity remained stable, SparCC network analysis revealed increases in connectivity measures such as edge count and clustering coefficient, indicating denser microbial interactions and greater community coordination after probiotic supplementation. Functional profiling showed trends toward increased microbial activity in fatty acid biosynthesis, NAD salvage, and starch degradation pathways. This pilot study provides initial evidence that probiotics may modulate structural and functional properties of the GM, with potential links to improved behavioural outcomes in children with FXS. Larger, controlled trials are needed to validate the therapeutic potential of GM-targeted interventions in FXS and related NDDs. Keywords FMR1 gene, Fragile X syndrome, Probiotics, Behaviour, Microbiome, Gut-brain axis Abbreviations ABC-C ABC-C FX AE AMR ASD BMI CARD Aberrant Behaviour Checklist-Community Aberrant Behaviour Checklist-Community in Fragile X Syndrome Adverse event Antimicrobial resistance Autism sprectrum disorder Body mass index Comprehensive Antibiotic Resistance Database 1Department of Pharmacology, Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia. 2Special Hospital for Cerebral Palsy and Developmental Neurology, Belgrade, Serbia. 3Institute for Rehabilitation, Belgrade, Serbia. 4Faculty of Biology, Center for Human Molecular Genetics, University of Belgrade, Belgrade, Serbia. 5Institute of Epidemiology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia. 6Institute of Microbiology and Immunology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia. 7Molecular and Experimental Mycobacteriology Research Center Borstel, Borstel, Germany. 8Leibniz Research Alliance INFECTIONS, Borstel, Germany. 9Evolution of the Resistome, Research Center Borstel, Borstel, Germany. 10German Center for Infection Research (DZIF), Partner Site Hamburg- Lübeck-Borstel-Riems, Lübeck, Borstel, Germany. 􀀍 email: [dragana.protic@med.bg.ac. rs](dragana.protic@med.bg.ac. rs); [mmerker@fz-borstel.de](mmerker@fz-borstel.de) [www. nature.com/scientificreports/](www. nature.com/scientificreports/) CGG CGI-I CGI-SCNCMCSHQ CNS DNA EFSA ENA FDR FMTFMR1 FMRPFXS GM HPA axis HPMC IQR IRB KO MaAsLin2 miRNA NAD NDDs PCoA PCR/CE PedsQL PERMANOVA PWYQPSSCFAs SDSHCPDNSPSS SparCC Cytosine-Guanine-Guanine trinucleotide repeat Clinical Global Impression-Improvement Clinical Global Impression – Severity Collection Nationale de Cultures

FAQs

What probiotic regimen was used in the pilot study?

The trial provided a daily probiotic formulation containing Lactobacillus casei, Lactobacillus salivarius, and Bifidobacterium breve for 12 weeks.

Which behavioral areas showed significant improvement after probiotic intake?

Irritability, communication, socialization, and adaptive behavior improved significantly based on the reported statistical results.

What microbiome changes were observed despite stable overall diversity?

Overall microbial diversity remained stable, while SparCC network analysis showed increased connectivity such as edge count and clustering coefficient, indicating denser microbial interactions.

Sep 30, 2026

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