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Biotin Controls Intestinal Stem Cell Mitosis and Host-Microbiome Interactions

61 Pages Posted: 15 Mar 2021 Publication Status: Review Complete

See all articles by Constantina Neophytou

Constantina Neophytou

University of Cyprus - Department of Biological Sciences

Chrysoula Pitsouli

University of Cyprus - Department of Biological Sciences

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Abstract

Detrimental alterations in intestinal microbiota, known as dysbiosis, predispose to inflammation that can lead to tumorigenesis. We show that dysbiosis can also result from impaired intestinal stem cell (ISC) metabolism. We found that the Drosophila intestinal ISC-specific biotin transporter Smvt is necessary for Jak/Stat pathway-mediated ISC mitosis. ISC-specific Smvt silencing impairs intestinal maintenance, which can be partially-rescued by the human Smvt, encoded by SLC5A6. Smvt-deficient flies exhibit microbial dysbiosis, whereby the growth of Providencia sneebia, an opportunistic pathogen, is favored. Dysbiosis correlates with increased Nox expression, ROS and enterocyte apoptosis. Flies acquire biotin from their diet and microbiota. We found 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.

Suggested Citation

Neophytou, Constantina and Pitsouli, Chrysoula, Biotin Controls Intestinal Stem Cell Mitosis and Host-Microbiome Interactions. Available at SSRN: https://ssrn.com/abstract=3805159 or http://dx.doi.org/10.2139/ssrn.3805159
This version of the paper has not been formally peer reviewed.

Constantina Neophytou

University of Cyprus - Department of Biological Sciences ( email )

Cyprus

Chrysoula Pitsouli (Contact Author)

University of Cyprus - Department of Biological Sciences ( email )

Cyprus

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