Biotin controls intestinal stem cell mitosis and host-microbiome interactions

Area of Science:

• * Molecular Biology
• * Microbiology
• * Genetics

Background:

• * Diet significantly influences host metabolism and intestinal microbiome composition.
• * Intestinal stem cells (ISCs) are vital for maintaining gut homeostasis, regeneration, and preventing diseases like cancer.
• * Biotin, a B vitamin, plays essential roles in cellular metabolism and has been linked to gut health.

Purpose of the Study:

• * To investigate the role of the intestinal stem cell (ISC)-specific biotin transporter, Smvt, in Drosophila midgut homeostasis.
• * To determine Smvt's involvement in infection-induced regeneration and intestinal tumorigenesis.
• * To explore the therapeutic potential of modulating the gut microbiome with biotin.

Main Methods:

• * Utilized Drosophila melanogaster as a model organism to study ISC function.
• * Employed genetic silencing techniques to specifically knock down Smvt expression in ISCs.
• * Analyzed gut microbial composition, gene expression (Nox), reactive oxygen species (ROS) levels, and enterocyte apoptosis.
• * Assessed the impact of dietary biotin levels and commensal bacteria on ISC mitosis and tumor growth.

Main Results:

• * Smvt-mediated biotin transport in ISCs is essential for ISC mitosis and intestinal maintenance.
• * Smvt deficiency leads to microbial dysbiosis, favoring opportunistic pathogen growth and increasing oxidative stress and apoptosis.
• * Biotin-producing commensal bacteria can rescue impaired ISC mitosis during dietary biotin scarcity.
• * Both Smvt and gut commensals play a role in controlling intestinal tumor development.

Conclusions:

• * Biotin transport via Smvt is critical for maintaining Drosophila midgut homeostasis and regeneration.
• * Dysbiosis, driven by Smvt deficiency, exacerbates intestinal damage and promotes tumorigenesis.
• * Targeting the gut microbiome with biotin presents a potential therapeutic strategy for dysbiosis-associated diseases and cancer control.