Integrated analysis of metabolome and microbiome in a rat model of perimenopausal syndrome

Abstract

ABSTRACT The objectives of this study are to examine the disparities in serum and intestinal tissue metabolites between a perimenopausal rat model and control rats and to analyze the diversity and functionality of intestinal microorganisms to determine the potential correlation between intestinal flora and metabolites. We established a rat model of perimenopausal syndrome (PMS) and performed an integrated analysis of metabolome and microbiome. Orthogonal partial least-squares discriminant analysis scores and replacement tests indicated distinct separations of anion and cation levels between serum and intestinal samples of the model and control groups. Furthermore, lipids and lipid-like molecules constituted the largest percentage of HMDB compounds in both serum and intestinal tissues, followed by organic acids and derivatives, and organoheterocyclic compounds, with other compounds showing significant variability. Moreover, analysis of diversity and functional enrichment of the intestinal microflora and correlation analysis with metabolites revealed significant variability in the composition of the intestinal flora between the normal control and perimenopausal groups, with these differentially expressed intestinal flora strongly correlated with their metabolites. The findings of this study are expected to contribute to understanding the indications and contraindications for estrogen application in perimenopausal women and to aid in the development of appropriate therapeutic agents.IMPORTANCEIn this work, we employed 16S ribosomal RNA gene sequencing to analyze the gut microbes in stool samples. In addition, we conducted an ultra-high-performance liquid chromatography-tandem mass spectrometry-based metabolomics approach on gut tissue and serum obtained from rats with perimenopausal syndrome (PMS) and healthy controls. By characterizing the composition and metabolomic properties of gut microbes in PMS rats, we aim to enhance our understanding of their role in women’s health, emphasizing the significance of regulating gut microbes in the context of menopausal women’s well-being. We aim to provide a theoretical basis for the prevention and treatment of PMS in terms of gut microflora as well as metabolism.

Keywords

• perimenopausal syndrome
• gut microbes
• 16S ribosomal RNA gene sequencing
• metabolic profiles
• ultra-high-performance liquid chromatography-tandem mass spectrometry