| Polycystic ovary syndrome(PCOS)is prevalent endocrine disorder that affects women of reproductive age.PCOS not only leads to infertility and causes negative pregnancy outcome,but also triggers multiple metabolic abnormalities.Common treatments for PCOS include steroid hormone drugs and insulin sensitizing agents.Howerver,these drugs only exert limited therapeutic effects and may cause significant side effects.Over the past few years,dysbiosis of gut microbiota has been confirmed in PCOS patients.Besides,the disease phenotype of PCOS can be influenced by shaping the gut microbiota.Several clinical trials have indicated that probiotics,which are gut microbiota-targeting agents,improve PCOS phenotypes.However,the gut microbiome-related mechanism of probiotics to reduce PCOS symptoms is still unclear.In this study,the gut microbiota and the related metabolites were analyzed.Probiotics that can reduce PCOS symptoms were screened by a letrozole-induced rat model.The role of effective strains on gut endocrine and gut microbiome were analyzed to futher understand how these strains reduce PCOS symptoms.The main findings were listed as follows:1.The gut microbiome of PCOS patients was analyzed based on the high-throughput sequencing and metabolomics techniques.Compared with healthy women,species richness was increased but species evenness was not changed in PCOS patients.Faecalibacterium was enriched in both obese PCOS and non-obese patients.The overall composition of genus Lactobacillus was changed by PCOS but the microbial distribution of genus Bifidobacterium was not changed in PCOS patients.Meanwhile,the abundance of Lactobacillus plantarum was decreased in PCOS patients.Based on the gut metabolomics analysis,metabolites that were related to valine,leucine and isoleucine degradation,and vitamin B6 metabolism were significantly changed in PCOS patients.Metabolites that were related to nicotinate and nicotinamide metabolism were significantly changed by body mass index.2.Using a letrozole-induced rat model,seventeen lactic acid bacteria strains were screened for their ability to reduce PCOS symptoms.L.plantarum CCFM1019 attenuated the pathological changes in the ovaries and restored sex hormone levels.In addition to the protective effects against ovary pathological changes and sex steroid levels,L.plantarum CCFM1202 alleviated abnormal liver function.The ability of reducing PCOS symptoms varies between different L.plantarum strains.3.The effects of L.plantarum CCFM1019 on the gut microbiota and gut endocrine were analyzed.The gut butyrate concentration was increased by L.plantarum CCFM1019.Besides,short-chain fatty acid(SCFA)producers such as Lachnospira and Ruminococcus＿2 were enriched by L.plantarum CCFM1019.Due to the activation of colonic G protein-coupled receptor 41,the peptide YY(PYY)levels were increased in L.plantarum CCFM1019 treated rats.This may further alleviate PCOS symptoms through the regulation of hypothalamus-pituitary-ovary(HPO)axis.4.To produce resistant starches capable of augmenting different SCFAs in the distal intestine,maize starch was acylated with specific SCFAs.Our results indicated that acylated starch can release acetate,propionate,and butyrate into the caecum and colon.Treatment with butylated starch alleviated PCOS symptoms in letrozole-treated rats,whereas treatment with acetylated starch and propylated starch did not exhibit such effects.Furthermore,butylated starch stimulated the secretion of PYY into the serum by activating colonic G protein-coupled receptor 41,which further affected HPO axis.Roseburia,a butyrate producer was enriched in colon after butylated starch treatment and may have helped further to relieve PCOS symptoms.5.SCFA analysis indicated that the protective effects of L.plantarum CCFM1202 on PCOS symptoms was independent of butyrate.Therefore,the effect of L.plantarum CCFM1202 on gut microbiota,faecal metabolites and serum metabolites were analyzed.Alpha diversity was improved and beta diversity was significantly changed by L.plantarum CCFM1202.After L.plantarum CCFM1202 administration,Bifidobacterium was enriched in the gut.Besides,metabolites that were related to progestational hormone biosynthesis were significantly increased by L.plantarum CCFM1202 and this may explain how L.plantarum CCFM1202 reduce PCOS symptoms.The gut microbiota may involve in this effect as the adundance of Bifidobacterium,Candidatus＿Saccharimonas and ASF356 were correlated with serum progestational hormones. |
