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Effects of Yulin Tong Bu formula on modulating gut microbiota and fecal metabolite interactions in mice with polycystic ovary syndrome

ABSTRACT:

BACKGROUND: Polycystic ovarian syndrome (PCOS) is a common endocrine disorder characterized by hyperandrogenism, ovarian dysfunction and polycystic ovarian morphology. Gut microbiota dysbiosis and metabolite are associated with PCOS clinical parameters. Yulin Tong Bu formula (YLTB), a traditional Chinese medicine formula, has been recently indicated to be capable of ameliorating polycystic ovary symptoms and correcting abnormal glucose metabolism. However, the therapeutic mechanism of YLTB on PCOS has not been fully elucidated.

METHODS: A pseudo sterile mouse model was established during this 4-day acclimatization phase by giving the animals an antibiotic cocktail to remove the gut microbiota. Here, the therapeutic effects of YLTB on PCOS were investigated using dehydroepiandrosterone plus high-fat diet induced PCOS mice model. Female prepuberal mice were randomly divided into 3 groups; namely, the control group, PCOS group and YLTB (38.68 g/kg/day) group. To test whether this effect is associated with the gut microbiota, we performed 16S rRNA sequencing studies to analyze the fecal microbiota of mice. The relationships among metabolites, gut microbiota and PCOS phenotypes were further explored by using Spearman correlation analysis. Then, the effect of metabolite ferulic acid was then validated in PCOS mice.

RESULTS: Our results showed that YLTB treatment ameliorated PCOS features (ovarian dysfunction, delayed glucose clearance, decreased insulin sensitivity, deregulation of glucolipid metabolism and hormones, etc) and significantly attenuated PCOS gut microbiota dysbiosis. Spearman correlation analysis showed that metabolites such as ferulic acid and folic acid are negatively correlated with PCOS clinical parameters. The effect of ferulic acid was similar to that of YLTB. In addition, the bacterial species such as Bacteroides dorei and Bacteroides fragilis were found to be positively related to PCOS clinical parameters, using the association study analysis.

CONCLUSION: These results suggest that YLTB treatment systematically regulates the interaction between the gut microbiota and the associated metabolites to ameliorate PCOS, providing a solid theoretical basis for further validation of YLTB effect on human PCOS trials.

INSTRUMENT(S): Liquid Chromatography MS - negative - reverse phase, Liquid Chromatography MS - positive - reverse phase

SUBMITTER: lijuan fu

PROVIDER: MTBLS6736 | MetaboLights | 2023-02-02

REPOSITORIES: MetaboLights

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			Action	DRS
	MTBLS6736	Other
	FILES	Other
	a_MTBLS6736_LC-MS_negative_reverse-phase_metabolite_profiling.txt	Txt
	a_MTBLS6736_LC-MS_positive_reverse-phase_metabolite_profiling.txt	Txt
	files-all.json	Other

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Project description:On going efforts are directed at understanding the mutualism between the gut microbiota and the host in breast-fed versus formula-fed infants. Due to the lack of tissue biopsies, no investigators have performed a global transcriptional (gene expression) analysis of the developing human intestine in healthy infants. As a result, the crosstalk between the microbiome and the host transcriptome in the developing mucosal-commensal environment has not been determined. In this study, we examined the host intestinal mRNA gene expression and microbial DNA profiles in full term 3 month-old infants exclusively formula fed (FF) (n=6) or breast fed (BF) (n=6) from birth to 3 months. Host mRNA microarray measurements were performed using isolated intact sloughed epithelial cells in stool samples collected at 3 months. Microbial composition from the same stool samples was assessed by metagenomic pyrosequencing. Both the host mRNA expression and bacterial microbiome phylogenetic profiles provided strong feature sets that clearly classified the two groups of babies (FF and BF). To determine the relationship between host epithelial cell gene expression and the bacterial colony profiles, the host transcriptome and functionally profiled microbiome data were analyzed in a multivariate manner. From a functional perspective, analysis of the gut microbiota's metagenome revealed that characteristics associated with virulence differed between the FF and BF babies. Using canonical correlation analysis, evidence of multivariate structure relating eleven host immunity / mucosal defense-related genes and microbiome virulence characteristics was observed. These results, for the first time, provide insight into the integrated responses of the host and microbiome to dietary substrates in the early neonatal period. Our data suggest that systems biology and computational modeling approaches that integrate “-omic” information from the host and the microbiome can identify important mechanistic pathways of intestinal development affecting the gut microbiome in the first few months of life. KEYWORDS: infant, breast-feeding, infant formula, exfoliated cells, transcriptome, metagenome, multivariate analysis, canonical correlation analysis 12 samples, 2 groups

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Effects of Yulin Tong Bu formula on modulating gut microbiota and fecal metabolite interactions in mice with polycystic ovary syndrome

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