Biotin controls intestinal stem cell mitosis and host-microbiome interactions

Summary: Diet is a key regulator of metabolism and interacts with the intestinal microbiome. Here, we study the role of the Drosophila intestinal stem cell (ISC)-specific biotin transporter Smvt in midgut homeostasis, infection-induced regeneration, and tumorigenesis. We show that Smvt-transported b...

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Main Authors: Constantina Neophytou, Chrysoula Pitsouli
Format: Article
Language:English
Published: Elsevier 2022-03-01
Series:Cell Reports
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2211124722002418
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author Constantina Neophytou
Chrysoula Pitsouli
author_facet Constantina Neophytou
Chrysoula Pitsouli
author_sort Constantina Neophytou
collection DOAJ
description Summary: Diet is a key regulator of metabolism and interacts with the intestinal microbiome. Here, we study the role of the Drosophila intestinal stem cell (ISC)-specific biotin transporter Smvt in midgut homeostasis, infection-induced regeneration, and tumorigenesis. We show that Smvt-transported biotin in ISCs is necessary for ISC mitosis. Smvt deficiency impairs intestinal maintenance, which can be rescued by the human Smvt, encoded by SLC5A6. ISC-specific, Smvt-silenced flies exhibit microbial dysbiosis, whereby the growth of Providencia sneebia, an opportunistic pathogen, is favored. Dysbiosis correlates with increased Nox expression, reactive oxygen species (ROS), and enterocyte apoptosis. Flies acquire biotin from their diet and microbiota. We show that, when dietary biotin is scarce, biotin-producing commensals, e.g., E. coli, can rescue reduced ISC mitosis. Smvt and commensals also control intestinal tumor growth. Our findings suggest that direct modification of the gut microbiome by biotin can serve as an approach for the treatment of dysbiosis-promoted diseases and tumorigenesis control.
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spelling doaj.art-41afa9757fa04298a2e55886b6a7161e2022-12-21T16:43:11ZengElsevierCell Reports2211-12472022-03-013810110505Biotin controls intestinal stem cell mitosis and host-microbiome interactionsConstantina Neophytou0Chrysoula Pitsouli1Department of Biological Sciences, University of Cyprus, 1 University Avenue, Aglantzia 2109, CyprusDepartment of Biological Sciences, University of Cyprus, 1 University Avenue, Aglantzia 2109, Cyprus; Corresponding authorSummary: Diet is a key regulator of metabolism and interacts with the intestinal microbiome. Here, we study the role of the Drosophila intestinal stem cell (ISC)-specific biotin transporter Smvt in midgut homeostasis, infection-induced regeneration, and tumorigenesis. We show that Smvt-transported biotin in ISCs is necessary for ISC mitosis. Smvt deficiency impairs intestinal maintenance, which can be rescued by the human Smvt, encoded by SLC5A6. ISC-specific, Smvt-silenced flies exhibit microbial dysbiosis, whereby the growth of Providencia sneebia, an opportunistic pathogen, is favored. Dysbiosis correlates with increased Nox expression, reactive oxygen species (ROS), and enterocyte apoptosis. Flies acquire biotin from their diet and microbiota. We show that, when dietary biotin is scarce, biotin-producing commensals, e.g., E. coli, can rescue reduced ISC mitosis. Smvt and commensals also control intestinal tumor growth. Our findings suggest that direct modification of the gut microbiome by biotin can serve as an approach for the treatment of dysbiosis-promoted diseases and tumorigenesis control.http://www.sciencedirect.com/science/article/pii/S2211124722002418dysbiosisbiotinSmvtSLC5A6DrosophilaProvidencia sneebia
spellingShingle Constantina Neophytou
Chrysoula Pitsouli
Biotin controls intestinal stem cell mitosis and host-microbiome interactions
Cell Reports
dysbiosis
biotin
Smvt
SLC5A6
Drosophila
Providencia sneebia
title Biotin controls intestinal stem cell mitosis and host-microbiome interactions
title_full Biotin controls intestinal stem cell mitosis and host-microbiome interactions
title_fullStr Biotin controls intestinal stem cell mitosis and host-microbiome interactions
title_full_unstemmed Biotin controls intestinal stem cell mitosis and host-microbiome interactions
title_short Biotin controls intestinal stem cell mitosis and host-microbiome interactions
title_sort biotin controls intestinal stem cell mitosis and host microbiome interactions
topic dysbiosis
biotin
Smvt
SLC5A6
Drosophila
Providencia sneebia
url http://www.sciencedirect.com/science/article/pii/S2211124722002418
work_keys_str_mv AT constantinaneophytou biotincontrolsintestinalstemcellmitosisandhostmicrobiomeinteractions
AT chrysoulapitsouli biotincontrolsintestinalstemcellmitosisandhostmicrobiomeinteractions