Analysis of gut microbiota in patients with Williams–Beuren Syndrome reveals dysbiosis linked to clinical manifestations

Abstract

Williams–Beuren syndrome (WBS) is a multisystem genetic disease caused by the deletion of a region of 1.5–1.8 Mb on chromosome 7q11.23. The elastin gene seems to account for several comorbidities and distinct clinical features such including cardiovascular disease, connective tissue abnormalities, growth retardation, and gastrointestinal (GI) symptoms. Increasing evidence points to alterations in gut microbiota composition as a primary or secondary cause of some GI or extra-intestinal characteristics. In this study, we performed the first exploratory analysis of gut microbiota in WBS patients compared to healthy subjects (CTRLs) using 16S rRNA amplicon sequencing, by investigating the gut dysbiosis in relation to diseases and comorbidities. We found that patients with WBS have significant dysbiosis compared to age-matched CTRLs, characterized by an increase in proinflammatory bacteria such as Pseudomonas, Gluconacetobacter and Eggerthella, and a reduction of anti-inflammatory bacteria including Akkermansia and Bifidobacterium. Microbial biomarkers associated with weight gain, GI symptoms and hypertension were identified. Gut microbiota profiling could represent a new tool that characterise intestinal dysbiosis to complement the clinical management of these patients. In particular, the administration of microbial-based treatments, alongside traditional therapies, could help in reducing or preventing the burden of these symptoms and improve the quality of life of these patients.

Williams–Beuren syndrome shapes the gut microbiota metaproteome

“…has been already negatively associated with metabolic risk 35 . Reduction of Firmicutes was also evidenced in WBSs patients by metataxonomy 19 . Anyway, metaproteomic results were not completely overlapping to that obtained by the previous cited 16S rRNA-based metagenomic study.…”

“…This evidence led us to speculate a major role of the WBS disease phenotype in the shaping of the GM functional signatures, compared to age dependency. Indeed, a previous 16S rRNA-based metagenomic study revealed the absence of statistically significant differences amongst age for the WBS group excluding the variable age as confounding factor, and provided interesting results comparing the WBSs to age-matched healthy subjects 19 . Therefore, we proceeded by analyzing all WBS samples and comparing them to the CTRL group, regardless of age, to establish a comprehensive understanding of the WBS impact on GM functionality.…”

“…However, a specific GM functional disease related-pattern was provided by both multivariate and univariate analyses: WBS-related GM functional signatures appeared linked to protein biosynthesis, biogenesis of cellular structures, and metabolic pathways related to amino acid, carbohydrate, and energy production, as already inferred from the targeted metagenomic approach performed on the same cohort of patients 19 . In particular, the differential expression of Glyceraldehyde-3-phosphate dehydrogenase and Ferredoxin highlighted a modulation of the Glycolysis/Gluconeogenesis pathway, while the differential expression of Pyruvate-formate lyase and Acetate kinase suggested a modulation of the metabolic patterns downstream the pyruvate cycle, and towards formate and acetyl-CoA dependent acetate production (Supplementary Figure 9).…”

Effects of single-anastomosis duodenal–ileal bypass with sleeve gastrectomy on gut microbiota and glucose metabolism in rats with type 2 diabetes

“…In contrast, our study demonstrated that SADI-S significantly increased the abundance of the phylum Verrucomicrobiota. Akkermansia , belonging to the phylum Verrucomicrobia, is an anti-inflammatory bacteria ( Luo et al, 2022 ; Del Chierico et al, 2023 ), and its abundance is negatively correlated with the level of insulin resistance ( Dao et al, 2016 ; Plovier et al, 2017 ; Konturek et al, 2018 ). We also found that the abundance of Akkermansia was significantly increased after SADI-S, concomitant with the significant improvement of T2D.…”

“…Thus, Coriobacteriaceae may play a vital role in bariatric surgery regulating host glucose homeostasis. Bifidobacterium , belonging to the phylum Actinomycetota, is also an anti-inflammatory bacteria ( Luo et al, 2022 ; Del Chierico et al, 2023 ). The abundance of Bifidobacterium decreases in patients with T2D and increases with BPD/DS and duodenal jejunal bypass ( Mukorako et al, 2019 ; Yu et al, 2020 ), consistent with our findings.…”