AUTHOR=Dai Ruoxi , Huang Jianqin , Cui Liyuan , Sun Ruiqi , Qiu Xuemin , Wang Yan , Sun Yan 

TITLE=Gut microbiota and metabolites in estrus cycle and their changes in a menopausal transition rat model with typical neuroendocrine aging

JOURNAL=Frontiers in Endocrinology

VOLUME=Volume 14 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2023.1282694

DOI=10.3389/fendo.2023.1282694

ISSN=1664-2392

ABSTRACT=Background: Neuroendocrine alterations in the mid-life hypothalamus coupled with reproductive decline herald the initiation of menopausal transition. The certain feature and contribution of gut microflora and metabolites to neuroendocrine changes in the menopausal transition remain largely unknown.Methods: Fecal samples of rats experiencing different reproductive stages were collected and processed for 16S rRNA and liquid chromatography-mass spectrometry sequencing. The differences of gut microbiota and metabolites between young and middle-aged rats during proestrus and diestrus were analyzed and their relationships to neuroendocrine aging were then examined.Results: At the genus level, the abundances of Anaeroyorax, Rikenella, Tyzzerella_3 and Atopostipes were abundant at proestrus while Romboutsia, Turicibacter, Clostridium_sensu_stricto_1, Ruminococcaceae_NK4A214_group, CHKCI002, Ruminococcaceae_UCG-010, Staphylococcus, Family_XII_AD3011_group, Ruminococcaceae_ UCG-011 and Christensenellaceae_R_7_group were enriched in the diestrus of middle-aged rats. Instead, DNF00809, Phocea and Lachnospiraceae_UCG-006 were found abundant during proestrus while Bacteroidetes, Lactobacillus, Erysipelatoclostridium, Anaeroplasma, Anaerofustis, Parasutterella and Enterococcus were enriched at the diestrus of young females. Discriminatory metabolites were identified involving in 90 metabolic pathways among the animal sets, which were enriched for the steroid hormone biosynthesis, arachidonic metabolism, primary bile acid synthesis, and ovarian steroidogenesis. Twenty-one metabolites lacking in hormone-associated changes in the middle-aged females presented positive or negative correlations with the circulating luteinizing hormone, bile acid, fibroblast growth factor 19 and gut hormones. Moreover, close correlations were detected between the intestinal bacteria and their metabolites.Conclusions: This study documents specific gut microbial composition changes and concomitant shifting trends of metabolites during menopausal transition, which may initiate the gut-brain dysfunction in neuroendocrine aging.