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Biology subjects

Sudi, S.

Publications and source records attributed to Sudi, S..

2 recordsLinked to original sources

Supplementation with a Limosilactobacillus fermentum K73 synbiotic modulates gut microbiota function and behavior in gnotobiotic mice transplanted with microbiota from children diagnosed with autism spectrum disorder

BackgroundGut dysbiosis has been implicated in numerous pathological conditions, including neurodevelopmental and neurodegenerative disorders. Recently, dietary interventions targeted at restoring microbial balance have therefore gained attention as potential therapeutic strategies. We recently demonstrated that an encapsulated synbiotic containing high-oleic palm oil and Limosilactobacillus fermentum K73 can modulate the metabolic activity and composition of human-derived gut microbiota in an in vitro batch bioreactor. Here, we extended this work through an in vivo supplementation pilot study using gnotobiotic mice colonized with gut microbiota from Colombian pediatric patients diagnosed with autism spectrum disorder (ASD) or age-matched neurotypical (NT) donors. Behavioral assessments and analyses of gut microbiota composition and function were performed before and after synbiotic supplementation. ResultsFirst, we found that the gut microbiota from Colombian ASD patients exhibited significantly reduced richness relative to NT donors, consistent with reports from other geographical regions, and displayed distinct compositional features unique to this population. Humanization of the gnotobiotic mice with this donor microbiota was successful, with murine gut communities reflecting features of their corresponding donor microbiota. Notably, synbiotic supplementation induced significant increases in the abundance of beneficial taxa and the production of short chain fatty acids that were more pronounced in mice colonized with ASD-derived microbiota, with concurrent behavioral changes associated with beneficial modulation of gut microbiota. ConclusionsOverall, we provide evidence that supports synbiotic supplementation as a viable strategy to positively modulate gut microbiome in conditions of dysbiosis. Our study also expands the body of knowledge of gut microbiome to understudied populations such as Latin America.

microbiology↗

Trymethylamine-N-oxide, a gut-derived metabolite, induces myofibroblastic activation of valvular interstitial cells through endoplasmic reticulum stress

Calcific aortic valve disease currently lacks effective treatments beyond surgical valve replacement, due to an incomplete understanding of its pathogenesis. Emerging evidence suggests that the gut microbiome influences cardiovascular health through the production of metabolites derived from dietary components. Among them, trimethylamine-N-oxide (TMAO) has been identified as a potential causal factor for several cardiovascular conditions. However, its role in the development of aortic valve disease remains poorly understood. This study sought to investigate the impact of TMAO on valvular interstitial cells (VICs), the most abundant cell type in the aortic valve. Here, we demonstrate that TMAO activates VICs towards a myofibroblastic profibrotic phenotype. Using an in vitro protocol to generate quiescent VICs, we found that TMAO induces the upregulation of myofibroblastic markers in a sex-independent manner. These quiescent VICs were more sensitive to TMAO than conventionally cultured VICs. Treatment with TMAO also elevated extracellular matrix production and oxidative stress, phenotypic hallmarks of an activated profibrotic state. Finally, inhibition of the endoplasmic reticulum stress kinase prior to TMAO treatment blocked all effects of this metabolite. These findings suggest that TMAO contributes to the early stages of valve disease by promoting VIC activation through endoplasmic reticulum stress mechanisms. Understanding the role of TMAO and other gut-derived metabolites in the pathogenesis of valve disease could inform the development of novel preventive or therapeutic strategies to modify or delay disease progression. Furthermore, these insights underscore the importance of host-microbiome interactions and highlight the potential for targeted dietary interventions to mitigate cardiovascular disease risk.

cell biology↗