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Curcumin β-D-Glucuronide Modulates an Autoimmune Model of Multiple Sclerosis with Altered Gut Microbiota in the Ileum and Feces

We developed a prodrug type of curcumin, curcumin monoglucuronide (CMG), whose intravenous/intraperitoneal injection achieves a high serum concentration of free-form curcumin. Although curcumin has been reported to alter the gut microbiota and immune responses, it is unclear whether the altered micr...

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Autores principales: Khadka, Sundar, Omura, Seiichi, Sato, Fumitaka, Nishio, Kazuto, Kakeya, Hideaki, Tsunoda, Ikuo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8677657/
https://www.ncbi.nlm.nih.gov/pubmed/34926318
http://dx.doi.org/10.3389/fcimb.2021.772962
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author Khadka, Sundar
Omura, Seiichi
Sato, Fumitaka
Nishio, Kazuto
Kakeya, Hideaki
Tsunoda, Ikuo
author_facet Khadka, Sundar
Omura, Seiichi
Sato, Fumitaka
Nishio, Kazuto
Kakeya, Hideaki
Tsunoda, Ikuo
author_sort Khadka, Sundar
collection PubMed
description We developed a prodrug type of curcumin, curcumin monoglucuronide (CMG), whose intravenous/intraperitoneal injection achieves a high serum concentration of free-form curcumin. Although curcumin has been reported to alter the gut microbiota and immune responses, it is unclear whether the altered microbiota could be associated with inflammation in immune-mediated diseases, such as multiple sclerosis (MS). We aimed to determine whether CMG administration could affect the gut microbiota at three anatomical sites (feces, ileal contents, and the ileal mucosa), leading to suppression of inflammation in the central nervous system (CNS) in an autoimmune model for MS, experimental autoimmune encephalomyelitis (EAE). We injected EAE mice with CMG, harvested the brains and spinal cords for histological analyses, and conducted microbiome analyses using 16S rRNA sequencing. CMG administration modulated EAE clinically and histologically, and altered overall microbiota compositions in feces and ileal contents, but not the ileal mucosa. Principal component analysis (PCA) of the microbiome showed that principal component (PC) 1 values in ileal contents, but not in feces, correlated with the clinical and histological EAE scores. On the other hand, when we analyzed the individual bacteria of the microbiota, the EAE scores correlated with significant increases in the relative abundance of two bacterial species at each anatomical site: Ruminococcus bromii and Blautia (Ruminococcus) gnavus in feces, Turicibacter sp. and Alistipes finegoldii in ileal contents, and Burkholderia spp. and Azoarcus spp. in the ileal mucosa. Therefore, CMG administration could alter the gut microbiota at the three different sites differentially in not only the overall gut microbiome compositions but also the abundance of individual bacteria, each of which was associated with modulation of neuroinflammation.
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spelling pubmed-86776572021-12-18 Curcumin β-D-Glucuronide Modulates an Autoimmune Model of Multiple Sclerosis with Altered Gut Microbiota in the Ileum and Feces Khadka, Sundar Omura, Seiichi Sato, Fumitaka Nishio, Kazuto Kakeya, Hideaki Tsunoda, Ikuo Front Cell Infect Microbiol Cellular and Infection Microbiology We developed a prodrug type of curcumin, curcumin monoglucuronide (CMG), whose intravenous/intraperitoneal injection achieves a high serum concentration of free-form curcumin. Although curcumin has been reported to alter the gut microbiota and immune responses, it is unclear whether the altered microbiota could be associated with inflammation in immune-mediated diseases, such as multiple sclerosis (MS). We aimed to determine whether CMG administration could affect the gut microbiota at three anatomical sites (feces, ileal contents, and the ileal mucosa), leading to suppression of inflammation in the central nervous system (CNS) in an autoimmune model for MS, experimental autoimmune encephalomyelitis (EAE). We injected EAE mice with CMG, harvested the brains and spinal cords for histological analyses, and conducted microbiome analyses using 16S rRNA sequencing. CMG administration modulated EAE clinically and histologically, and altered overall microbiota compositions in feces and ileal contents, but not the ileal mucosa. Principal component analysis (PCA) of the microbiome showed that principal component (PC) 1 values in ileal contents, but not in feces, correlated with the clinical and histological EAE scores. On the other hand, when we analyzed the individual bacteria of the microbiota, the EAE scores correlated with significant increases in the relative abundance of two bacterial species at each anatomical site: Ruminococcus bromii and Blautia (Ruminococcus) gnavus in feces, Turicibacter sp. and Alistipes finegoldii in ileal contents, and Burkholderia spp. and Azoarcus spp. in the ileal mucosa. Therefore, CMG administration could alter the gut microbiota at the three different sites differentially in not only the overall gut microbiome compositions but also the abundance of individual bacteria, each of which was associated with modulation of neuroinflammation. Frontiers Media S.A. 2021-12-03 /pmc/articles/PMC8677657/ /pubmed/34926318 http://dx.doi.org/10.3389/fcimb.2021.772962 Text en Copyright © 2021 Khadka, Omura, Sato, Nishio, Kakeya and Tsunoda https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cellular and Infection Microbiology
Khadka, Sundar
Omura, Seiichi
Sato, Fumitaka
Nishio, Kazuto
Kakeya, Hideaki
Tsunoda, Ikuo
Curcumin β-D-Glucuronide Modulates an Autoimmune Model of Multiple Sclerosis with Altered Gut Microbiota in the Ileum and Feces
title Curcumin β-D-Glucuronide Modulates an Autoimmune Model of Multiple Sclerosis with Altered Gut Microbiota in the Ileum and Feces
title_full Curcumin β-D-Glucuronide Modulates an Autoimmune Model of Multiple Sclerosis with Altered Gut Microbiota in the Ileum and Feces
title_fullStr Curcumin β-D-Glucuronide Modulates an Autoimmune Model of Multiple Sclerosis with Altered Gut Microbiota in the Ileum and Feces
title_full_unstemmed Curcumin β-D-Glucuronide Modulates an Autoimmune Model of Multiple Sclerosis with Altered Gut Microbiota in the Ileum and Feces
title_short Curcumin β-D-Glucuronide Modulates an Autoimmune Model of Multiple Sclerosis with Altered Gut Microbiota in the Ileum and Feces
title_sort curcumin β-d-glucuronide modulates an autoimmune model of multiple sclerosis with altered gut microbiota in the ileum and feces
topic Cellular and Infection Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8677657/
https://www.ncbi.nlm.nih.gov/pubmed/34926318
http://dx.doi.org/10.3389/fcimb.2021.772962
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