Williams-Beuren syndrome shapes the gut microbiota metaproteome

Williams-Beuren syndrome (WBS) is a rare genetic neurodevelopmental disorder with multi-systemic manifestations. The evidence that most subjects with WBS face gastrointestinal (GI) comorbidities, have prompted us to carry out a metaproteomic investigation of their gut microbiota (GM) profile compared to age-matched healthy subjects (CTRLs). Metaproteomic analysis was carried out on fecal samples collected from 41 individuals with WBS, and compared with samples from 45 CTRLs. Stool were extracted for high yield in bacterial protein group (PG) content, trypsin-digested and analysed by nanoLiquid Chromatography-Mass Spectrometry. Label free quantification, taxonomic assignment by the lowest common ancestor (LCA) algorithm and functional annotations by COG and KEGG databases were performed. Data were statistically interpreted by multivariate and univariate analyses. A WBS GM functional dissimilarity respect to CTRLs, regardless age distribution, was reported. The alterations in function of WBSs GM was primarily based on bacterial pathways linked to carbohydrate transport and metabolism and energy production. Influence of diet, obesity, and GI symptoms was assessed, highlighting changes in GM biochemical patterns, according to WBS subsets' stratification. The LCA-derived ecology unveiled WBS-related functionally active bacterial signatures: Bacteroidetes related to over-expressed PGs, and Firmicutes, specifically the specie Faecalibacterium prausnitzii, linked to under-expressed PGs, suggesting a depletion of beneficial bacteria. These new evidences on WBS gut dysbiosis may offer novel targets for tailored interventions.