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:	Sundar Khadka, Seiichi Omura, Fumitaka Sato, Kazuto Nishio, Hideaki Kakeya, Ikuo Tsunoda
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	bioinformatics animal model pattern matching PICRUSt analysis bacterial taxonomy Alpha diversity Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/b1ab5539dccd4d6489c288f6f55bc212
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spelling	oai:doaj.org-article:b1ab5539dccd4d6489c288f6f55bc2122021-12-03T04:29:31ZCurcumin β-D-Glucuronide Modulates an Autoimmune Model of Multiple Sclerosis with Altered Gut Microbiota in the Ileum and Feces2235-298810.3389/fcimb.2021.772962https://doaj.org/article/b1ab5539dccd4d6489c288f6f55bc2122021-12-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fcimb.2021.772962/fullhttps://doaj.org/toc/2235-2988We 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.Sundar KhadkaSeiichi OmuraFumitaka SatoKazuto NishioHideaki KakeyaIkuo TsunodaFrontiers Media S.A.articlebioinformaticsanimal modelpattern matchingPICRUSt analysisbacterial taxonomyAlpha diversityMicrobiologyQR1-502ENFrontiers in Cellular and Infection Microbiology, Vol 11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	bioinformatics animal model pattern matching PICRUSt analysis bacterial taxonomy Alpha diversity Microbiology QR1-502
spellingShingle	bioinformatics animal model pattern matching PICRUSt analysis bacterial taxonomy Alpha diversity Microbiology QR1-502 Sundar Khadka Seiichi Omura Fumitaka Sato Kazuto Nishio Hideaki Kakeya Ikuo Tsunoda Curcumin β-D-Glucuronide Modulates an Autoimmune Model of Multiple Sclerosis with Altered Gut Microbiota in the Ileum and Feces
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.
format	article
author	Sundar Khadka Seiichi Omura Fumitaka Sato Kazuto Nishio Hideaki Kakeya Ikuo Tsunoda
author_facet	Sundar Khadka Seiichi Omura Fumitaka Sato Kazuto Nishio Hideaki Kakeya Ikuo Tsunoda
author_sort	Sundar Khadka
title	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_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_sort	curcumin β-d-glucuronide modulates an autoimmune model of multiple sclerosis with altered gut microbiota in the ileum and feces
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/b1ab5539dccd4d6489c288f6f55bc212
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Curcumin β-D-Glucuronide Modulates an Autoimmune Model of Multiple Sclerosis with Altered Gut Microbiota in the Ileum and Feces

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