๐ก WilliamsโBeuren syndrome (WBS) is a rare genetic neurodevelopmental disorder with multi-systemic manifestations.
๐ To gain insights into the gut microbiota (GM) of individuals with WBS, a metaproteomic investigation was conducted, comparing the GM profile of WBS patients to age-matched healthy subjects (CTRLs).
๐ Methods
Sample Collection: Stool samples were collected from 41 individuals with WBS and 45 CTRLs. The study cohort covered a wide age range, from 1 to 42 years, to explore the potential influence of age on GM. High bacterial protein group (PG) content was extracted from the samples.
Metaproteomic Analysis: Stool samples were trypsin-digested and analyzed using nanoLiquid Chromatography-Mass Spectrometry. Label-free quantification, taxonomic assignment by the lowest common ancestor (LCA) algorithm, and functional annotations using COG and KEGG databases were performed.
Data Analysis: Multivariate and univariate analyses were employed to interpret the data, uncover differences in GM functionality, and investigate the impact of age, diet, obesity, and GI symptoms.
๐ Key Findings
WBS-Related GM Functional Differences: The study revealed distinct GM functional profiles in individuals with WBS compared to CTRLs, irrespective of age distribution. These functional differences were primarily associated with pathways related to carbohydrate transport, metabolism, and energy production.
Impact of Age: Surprisingly, age did not significantly affect the composition of GM in individuals with WBS, in contrast to the CTRL group. This finding suggests that WBS disease phenotype may play a more substantial role in shaping GM functionality than age.
Influence of Disease Subsets: Patients with non-omnivorous diets, obesity, and GI symptoms exhibited specific GM alterations. These individuals displayed changes in GM biochemical patterns, reflecting worsening gut eubiosis.
Ecological Patterns: Taxonomic assignments identified Bacteroidetes as the primary phylum associated with over-expressed bacterial PGs in WBS GM, while Firmicutes was linked to under-expressed PGs. The ratio of Firmicutes/Bacteroidetes is considered a marker for dysbiosis in inflammatory diseases.
Depletion of Butyrogenic Bacteria: The metaproteomic analysis suggested a decrease in butyrate-producing bacteria in WBS GM, with specific emphasis on ๐๐ข๐ฆ๐ค๐ข๐ญ๐ช๐ฃ๐ข๐ค๐ต๐ฆ๐ณ๐ช๐ถ๐ฎ ๐ฑ๐ณ๐ข๐ถ๐ด๐ฏ๐ช๐ต๐ป๐ช๐ช. The depletion of these beneficial bacteria may contribute to the disease phenotype.
Inflammatory State: PGs associated with inflammation and neutrophil degranulation were up-regulated in WBS GM, suggesting an inflamed state in the intestines.
๐ The study highlighted the role of GM in carbohydrate metabolism, energy production, and inflammation in individuals with WBS. This study provides a potential target for tailored interventions, such as probiotics and postbiotics, to enhance the GI health of WBS patients.
Link to The Article : https://tinyurl.com/3x3azc8h
