Gut microbiota–bile acid–interleukin-22 axis orchestrates polycystic ovary syndrome

Xinyu Qi, Chuyu Yun, Lulu Sun, Jialin Xia, Qing Wu, Ying Wang, Lina Wang, Yangming Zhang, Xianyi Liang, Liying Wang, Frank J. Gonzalez, Andrew David Patterson, Huiying Liu, Liangshan Mu, Zehong Zhou, Yue Zhao, Rong Li, Ping Liu, Chao Zhong, Yanli PangChangtao Jiang, Jie Qiao

Research output: Contribution to journalLetter

2 Citations (Scopus)

Abstract

Polycystic ovary syndrome (PCOS) is characterized by androgen excess, ovulatory dysfunction and polycystic ovaries1, and is often accompanied by insulin resistance2. The mechanism of ovulatory dysfunction and insulin resistance in PCOS remains elusive, thus limiting the development of therapeutics. Improved metabolic health is associated with a relatively high microbiota gene content and increased microbial diversity3,4. This study aimed to investigate the impact of the gut microbiota and its metabolites on the regulation of PCOS-associated ovarian dysfunction and insulin resistance. Here, we report that Bacteroides vulgatus was markedly elevated in the gut microbiota of individuals with PCOS, accompanied by reduced glycodeoxycholic acid and tauroursodeoxycholic acid levels. Transplantation of fecal microbiota from women with PCOS or B. vulgatus-colonized recipient mice resulted in increased disruption of ovarian functions, insulin resistance, altered bile acid metabolism, reduced interleukin-22 secretion and infertility. Mechanistically, glycodeoxycholic acid induced intestinal group 3 innate lymphoid cell IL-22 secretion through GATA binding protein 3, and IL-22 in turn improved the PCOS phenotype. This finding is consistent with the reduced levels of IL-22 in individuals with PCOS. This study suggests that modifying the gut microbiota, altering bile acid metabolism and/or increasing IL-22 levels may be of value for the treatment of PCOS.

Original languageEnglish (US)
Pages (from-to)1225-1233
Number of pages9
JournalNature Medicine
Volume25
Issue number8
DOIs
StatePublished - Aug 1 2019

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Polycystic Ovary Syndrome
Glycodeoxycholic Acid
Insulin
Bile Acids and Salts
Metabolism
Insulin Resistance
Metabolites
Androgens
Carrier Proteins
Genes
Bacteroides
interleukin-22
Health
Microbiota
Infertility
Lymphocytes
Phenotype
Therapeutics

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Qi, X., Yun, C., Sun, L., Xia, J., Wu, Q., Wang, Y., ... Qiao, J. (2019). Gut microbiota–bile acid–interleukin-22 axis orchestrates polycystic ovary syndrome. Nature Medicine, 25(8), 1225-1233. https://doi.org/10.1038/s41591-019-0509-0
Qi, Xinyu ; Yun, Chuyu ; Sun, Lulu ; Xia, Jialin ; Wu, Qing ; Wang, Ying ; Wang, Lina ; Zhang, Yangming ; Liang, Xianyi ; Wang, Liying ; Gonzalez, Frank J. ; Patterson, Andrew David ; Liu, Huiying ; Mu, Liangshan ; Zhou, Zehong ; Zhao, Yue ; Li, Rong ; Liu, Ping ; Zhong, Chao ; Pang, Yanli ; Jiang, Changtao ; Qiao, Jie. / Gut microbiota–bile acid–interleukin-22 axis orchestrates polycystic ovary syndrome. In: Nature Medicine. 2019 ; Vol. 25, No. 8. pp. 1225-1233.
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abstract = "Polycystic ovary syndrome (PCOS) is characterized by androgen excess, ovulatory dysfunction and polycystic ovaries1, and is often accompanied by insulin resistance2. The mechanism of ovulatory dysfunction and insulin resistance in PCOS remains elusive, thus limiting the development of therapeutics. Improved metabolic health is associated with a relatively high microbiota gene content and increased microbial diversity3,4. This study aimed to investigate the impact of the gut microbiota and its metabolites on the regulation of PCOS-associated ovarian dysfunction and insulin resistance. Here, we report that Bacteroides vulgatus was markedly elevated in the gut microbiota of individuals with PCOS, accompanied by reduced glycodeoxycholic acid and tauroursodeoxycholic acid levels. Transplantation of fecal microbiota from women with PCOS or B. vulgatus-colonized recipient mice resulted in increased disruption of ovarian functions, insulin resistance, altered bile acid metabolism, reduced interleukin-22 secretion and infertility. Mechanistically, glycodeoxycholic acid induced intestinal group 3 innate lymphoid cell IL-22 secretion through GATA binding protein 3, and IL-22 in turn improved the PCOS phenotype. This finding is consistent with the reduced levels of IL-22 in individuals with PCOS. This study suggests that modifying the gut microbiota, altering bile acid metabolism and/or increasing IL-22 levels may be of value for the treatment of PCOS.",
author = "Xinyu Qi and Chuyu Yun and Lulu Sun and Jialin Xia and Qing Wu and Ying Wang and Lina Wang and Yangming Zhang and Xianyi Liang and Liying Wang and Gonzalez, {Frank J.} and Patterson, {Andrew David} and Huiying Liu and Liangshan Mu and Zehong Zhou and Yue Zhao and Rong Li and Ping Liu and Chao Zhong and Yanli Pang and Changtao Jiang and Jie Qiao",
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Qi, X, Yun, C, Sun, L, Xia, J, Wu, Q, Wang, Y, Wang, L, Zhang, Y, Liang, X, Wang, L, Gonzalez, FJ, Patterson, AD, Liu, H, Mu, L, Zhou, Z, Zhao, Y, Li, R, Liu, P, Zhong, C, Pang, Y, Jiang, C & Qiao, J 2019, 'Gut microbiota–bile acid–interleukin-22 axis orchestrates polycystic ovary syndrome', Nature Medicine, vol. 25, no. 8, pp. 1225-1233. https://doi.org/10.1038/s41591-019-0509-0

Gut microbiota–bile acid–interleukin-22 axis orchestrates polycystic ovary syndrome. / Qi, Xinyu; Yun, Chuyu; Sun, Lulu; Xia, Jialin; Wu, Qing; Wang, Ying; Wang, Lina; Zhang, Yangming; Liang, Xianyi; Wang, Liying; Gonzalez, Frank J.; Patterson, Andrew David; Liu, Huiying; Mu, Liangshan; Zhou, Zehong; Zhao, Yue; Li, Rong; Liu, Ping; Zhong, Chao; Pang, Yanli; Jiang, Changtao; Qiao, Jie.

In: Nature Medicine, Vol. 25, No. 8, 01.08.2019, p. 1225-1233.

Research output: Contribution to journalLetter

TY - JOUR

T1 - Gut microbiota–bile acid–interleukin-22 axis orchestrates polycystic ovary syndrome

AU - Qi, Xinyu

AU - Yun, Chuyu

AU - Sun, Lulu

AU - Xia, Jialin

AU - Wu, Qing

AU - Wang, Ying

AU - Wang, Lina

AU - Zhang, Yangming

AU - Liang, Xianyi

AU - Wang, Liying

AU - Gonzalez, Frank J.

AU - Patterson, Andrew David

AU - Liu, Huiying

AU - Mu, Liangshan

AU - Zhou, Zehong

AU - Zhao, Yue

AU - Li, Rong

AU - Liu, Ping

AU - Zhong, Chao

AU - Pang, Yanli

AU - Jiang, Changtao

AU - Qiao, Jie

PY - 2019/8/1

Y1 - 2019/8/1

N2 - Polycystic ovary syndrome (PCOS) is characterized by androgen excess, ovulatory dysfunction and polycystic ovaries1, and is often accompanied by insulin resistance2. The mechanism of ovulatory dysfunction and insulin resistance in PCOS remains elusive, thus limiting the development of therapeutics. Improved metabolic health is associated with a relatively high microbiota gene content and increased microbial diversity3,4. This study aimed to investigate the impact of the gut microbiota and its metabolites on the regulation of PCOS-associated ovarian dysfunction and insulin resistance. Here, we report that Bacteroides vulgatus was markedly elevated in the gut microbiota of individuals with PCOS, accompanied by reduced glycodeoxycholic acid and tauroursodeoxycholic acid levels. Transplantation of fecal microbiota from women with PCOS or B. vulgatus-colonized recipient mice resulted in increased disruption of ovarian functions, insulin resistance, altered bile acid metabolism, reduced interleukin-22 secretion and infertility. Mechanistically, glycodeoxycholic acid induced intestinal group 3 innate lymphoid cell IL-22 secretion through GATA binding protein 3, and IL-22 in turn improved the PCOS phenotype. This finding is consistent with the reduced levels of IL-22 in individuals with PCOS. This study suggests that modifying the gut microbiota, altering bile acid metabolism and/or increasing IL-22 levels may be of value for the treatment of PCOS.

AB - Polycystic ovary syndrome (PCOS) is characterized by androgen excess, ovulatory dysfunction and polycystic ovaries1, and is often accompanied by insulin resistance2. The mechanism of ovulatory dysfunction and insulin resistance in PCOS remains elusive, thus limiting the development of therapeutics. Improved metabolic health is associated with a relatively high microbiota gene content and increased microbial diversity3,4. This study aimed to investigate the impact of the gut microbiota and its metabolites on the regulation of PCOS-associated ovarian dysfunction and insulin resistance. Here, we report that Bacteroides vulgatus was markedly elevated in the gut microbiota of individuals with PCOS, accompanied by reduced glycodeoxycholic acid and tauroursodeoxycholic acid levels. Transplantation of fecal microbiota from women with PCOS or B. vulgatus-colonized recipient mice resulted in increased disruption of ovarian functions, insulin resistance, altered bile acid metabolism, reduced interleukin-22 secretion and infertility. Mechanistically, glycodeoxycholic acid induced intestinal group 3 innate lymphoid cell IL-22 secretion through GATA binding protein 3, and IL-22 in turn improved the PCOS phenotype. This finding is consistent with the reduced levels of IL-22 in individuals with PCOS. This study suggests that modifying the gut microbiota, altering bile acid metabolism and/or increasing IL-22 levels may be of value for the treatment of PCOS.

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