Cargando…

Integrated fecal microbiota and metabolomics analysis of the orlistat intervention effect on polycystic ovary syndrome rats induced by letrozole combined with a high-fat diet

BACKGROUND: This study aimed to compare the characteristics of the gut microbiota and their metabolite profiles between polycystic ovary syndrome (PCOS) and orlistat-treated PCOS rats (ORL-PCOS), which could help to better understand the underlying mechanism of the effect of orlistat on PCOS. METHOD...

Descripción completa

Detalles Bibliográficos
Autores principales: Yang, Jianmei, Wang, Enli, Jiang, Mingmin, Tan, Yujun, Yao, Fangfang, Sun, Chenghong, Pan, Lihong, Gao, Ling, Yao, Jingchun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10240724/
https://www.ncbi.nlm.nih.gov/pubmed/37277785
http://dx.doi.org/10.1186/s13048-023-01193-3
_version_ 1785053834316349440
author Yang, Jianmei
Wang, Enli
Jiang, Mingmin
Tan, Yujun
Yao, Fangfang
Sun, Chenghong
Pan, Lihong
Gao, Ling
Yao, Jingchun
author_facet Yang, Jianmei
Wang, Enli
Jiang, Mingmin
Tan, Yujun
Yao, Fangfang
Sun, Chenghong
Pan, Lihong
Gao, Ling
Yao, Jingchun
author_sort Yang, Jianmei
collection PubMed
description BACKGROUND: This study aimed to compare the characteristics of the gut microbiota and their metabolite profiles between polycystic ovary syndrome (PCOS) and orlistat-treated PCOS rats (ORL-PCOS), which could help to better understand the underlying mechanism of the effect of orlistat on PCOS. METHODS: PCOS rat models were established using letrozole combined with a high-fat diet. Ten rats were randomly selected as a PCOS control group (PCOS). The other three groups (n = 10/group) were additionally supplemented with different doses of orlistat (low, medium, high). Then, fecal samples of the PCOS and ORL-PCOS groups were analysed by 16S rRNA gene sequencing and untargeted metabolomics. Blood samples were collected to detect serum sex hormones and lipids. RESULTS: The results showed that orlistat attenuated the body weight gain, decreased the levels of T, LH, the LH/FSH ratio, TC, TG and LDL-C; increased the level of E2; and improved estrous cycle disorder in PCOS rats. The bacterial richness and diversity of the gut microbiota in the ORL-PCOS group were higher than those in the PCOS group. The ratio of Firmicutes to Bacteroidetes was decreased with orlistat treatment. Moreover, orlistat treatment led to a significant decrease in the relative abundance of Ruminococcaceae and Lactobacillaceae, and increases in the abundances of Muribaculaceae and Bacteroidaceae. Metabolic analysis identified 216 differential fecal metabolites in total and 6 enriched KEGG pathways between the two groups, including steroid hormone biosynthesis, neuroactive ligand-receptor interaction and vitamin digestion and absorption. Steroid hormone biosynthesis was the pathway with the most significant enrichment. The correlations between the gut microbiota and differential metabolites were calculated, which may provide a basis for understanding the composition and function of microbial communities. CONCLUSIONS: Our data suggested that orlistat exerts a PCOS treatment effect, which may be mediated by modifying the structure and composition of the gut microbiota, as well as the metabolite profiles of PCOS rats. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13048-023-01193-3.
format Online
Article
Text
id pubmed-10240724
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-102407242023-06-06 Integrated fecal microbiota and metabolomics analysis of the orlistat intervention effect on polycystic ovary syndrome rats induced by letrozole combined with a high-fat diet Yang, Jianmei Wang, Enli Jiang, Mingmin Tan, Yujun Yao, Fangfang Sun, Chenghong Pan, Lihong Gao, Ling Yao, Jingchun J Ovarian Res Research BACKGROUND: This study aimed to compare the characteristics of the gut microbiota and their metabolite profiles between polycystic ovary syndrome (PCOS) and orlistat-treated PCOS rats (ORL-PCOS), which could help to better understand the underlying mechanism of the effect of orlistat on PCOS. METHODS: PCOS rat models were established using letrozole combined with a high-fat diet. Ten rats were randomly selected as a PCOS control group (PCOS). The other three groups (n = 10/group) were additionally supplemented with different doses of orlistat (low, medium, high). Then, fecal samples of the PCOS and ORL-PCOS groups were analysed by 16S rRNA gene sequencing and untargeted metabolomics. Blood samples were collected to detect serum sex hormones and lipids. RESULTS: The results showed that orlistat attenuated the body weight gain, decreased the levels of T, LH, the LH/FSH ratio, TC, TG and LDL-C; increased the level of E2; and improved estrous cycle disorder in PCOS rats. The bacterial richness and diversity of the gut microbiota in the ORL-PCOS group were higher than those in the PCOS group. The ratio of Firmicutes to Bacteroidetes was decreased with orlistat treatment. Moreover, orlistat treatment led to a significant decrease in the relative abundance of Ruminococcaceae and Lactobacillaceae, and increases in the abundances of Muribaculaceae and Bacteroidaceae. Metabolic analysis identified 216 differential fecal metabolites in total and 6 enriched KEGG pathways between the two groups, including steroid hormone biosynthesis, neuroactive ligand-receptor interaction and vitamin digestion and absorption. Steroid hormone biosynthesis was the pathway with the most significant enrichment. The correlations between the gut microbiota and differential metabolites were calculated, which may provide a basis for understanding the composition and function of microbial communities. CONCLUSIONS: Our data suggested that orlistat exerts a PCOS treatment effect, which may be mediated by modifying the structure and composition of the gut microbiota, as well as the metabolite profiles of PCOS rats. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13048-023-01193-3. BioMed Central 2023-06-05 /pmc/articles/PMC10240724/ /pubmed/37277785 http://dx.doi.org/10.1186/s13048-023-01193-3 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Yang, Jianmei
Wang, Enli
Jiang, Mingmin
Tan, Yujun
Yao, Fangfang
Sun, Chenghong
Pan, Lihong
Gao, Ling
Yao, Jingchun
Integrated fecal microbiota and metabolomics analysis of the orlistat intervention effect on polycystic ovary syndrome rats induced by letrozole combined with a high-fat diet
title Integrated fecal microbiota and metabolomics analysis of the orlistat intervention effect on polycystic ovary syndrome rats induced by letrozole combined with a high-fat diet
title_full Integrated fecal microbiota and metabolomics analysis of the orlistat intervention effect on polycystic ovary syndrome rats induced by letrozole combined with a high-fat diet
title_fullStr Integrated fecal microbiota and metabolomics analysis of the orlistat intervention effect on polycystic ovary syndrome rats induced by letrozole combined with a high-fat diet
title_full_unstemmed Integrated fecal microbiota and metabolomics analysis of the orlistat intervention effect on polycystic ovary syndrome rats induced by letrozole combined with a high-fat diet
title_short Integrated fecal microbiota and metabolomics analysis of the orlistat intervention effect on polycystic ovary syndrome rats induced by letrozole combined with a high-fat diet
title_sort integrated fecal microbiota and metabolomics analysis of the orlistat intervention effect on polycystic ovary syndrome rats induced by letrozole combined with a high-fat diet
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10240724/
https://www.ncbi.nlm.nih.gov/pubmed/37277785
http://dx.doi.org/10.1186/s13048-023-01193-3
work_keys_str_mv AT yangjianmei integratedfecalmicrobiotaandmetabolomicsanalysisoftheorlistatinterventioneffectonpolycysticovarysyndromeratsinducedbyletrozolecombinedwithahighfatdiet
AT wangenli integratedfecalmicrobiotaandmetabolomicsanalysisoftheorlistatinterventioneffectonpolycysticovarysyndromeratsinducedbyletrozolecombinedwithahighfatdiet
AT jiangmingmin integratedfecalmicrobiotaandmetabolomicsanalysisoftheorlistatinterventioneffectonpolycysticovarysyndromeratsinducedbyletrozolecombinedwithahighfatdiet
AT tanyujun integratedfecalmicrobiotaandmetabolomicsanalysisoftheorlistatinterventioneffectonpolycysticovarysyndromeratsinducedbyletrozolecombinedwithahighfatdiet
AT yaofangfang integratedfecalmicrobiotaandmetabolomicsanalysisoftheorlistatinterventioneffectonpolycysticovarysyndromeratsinducedbyletrozolecombinedwithahighfatdiet
AT sunchenghong integratedfecalmicrobiotaandmetabolomicsanalysisoftheorlistatinterventioneffectonpolycysticovarysyndromeratsinducedbyletrozolecombinedwithahighfatdiet
AT panlihong integratedfecalmicrobiotaandmetabolomicsanalysisoftheorlistatinterventioneffectonpolycysticovarysyndromeratsinducedbyletrozolecombinedwithahighfatdiet
AT gaoling integratedfecalmicrobiotaandmetabolomicsanalysisoftheorlistatinterventioneffectonpolycysticovarysyndromeratsinducedbyletrozolecombinedwithahighfatdiet
AT yaojingchun integratedfecalmicrobiotaandmetabolomicsanalysisoftheorlistatinterventioneffectonpolycysticovarysyndromeratsinducedbyletrozolecombinedwithahighfatdiet