{"id":75,"title":"Alterations of fecal microbiome and metabolome in patients with diminished ovarian reserve","title_zh":"卵巢储备减退患者粪便微生物组与代谢组改变及其与卵巢功能的关联","url":"https://pubmed.ncbi.nlm.nih.gov/42982605","doi":"10.1093/humrep/deag163","pmid":"42982605","journal":"Hum Reprod","kind":"paper","lang":"en","published_at":"2026-11-04T00:00:00+00:00","fetched_at":"2026-11-08T03:43:53+00:00","authors":["Sun L","Li J","Zhu Y","Li D","Yin B","Kong H","Wang F","Guo Y","Zhang Y"],"primary_topic":"oocyte","topics":[{"slug":"oocyte","score":7.0,"hits":["antral follicle","ovarian","ovarian reserve","ovary"]},{"slug":"repro-endo","score":7.0,"hits":["amh","anti-müllerian","diminished ovarian reserve","dor"]},{"slug":"omics-methods","score":5.0,"hits":["metabolome","metabolomics"]},{"slug":"art-clinical","score":3.0,"hits":["frozen embryo transfer","infertile","infertility"]}],"topic_score":7.0,"preference_score":5.0,"preference_labels":["可转化到 ART 实验室的发现"],"llm_score":73.0,"final_score":82.0,"score_dims":{"novelty":70,"rigor":70,"impact":68,"relevance":88,"translation":62},"recommend_reason":"基于较多样本整合16S与代谢组学，发现DOR相关菌属和硬脂酸标志物，对肠-卵巢轴及DOR生物标志物研究有参考价值；但横断面设计、缺乏机制验证和年龄分层，临床转化仍需谨慎。","keywords":["卵巢储备减退","肠道微生物组","代谢组学","硬脂酸","肠-卵巢轴","PI3K-Akt"],"selected":1,"story_id":103,"llm_provider":"deepseek","llm_model":"deepseek-flash","llm_effort":"low","source_key":"pubmed-art","source_name":"PubMed · 辅助生殖临床","source_tier":1,"mention_count":3,"has_interpretation":false,"journal_key":"humrep","journal_tier":"field-top","journal_if":6.0,"is_mock":false,"summary_zh":"该横断面研究纳入190例接受冻融胚胎移植的女性（91例卵巢储备减退DOR、99例正常卵巢储备NOR），采集临床资料与粪便，行16S rRNA测序和非靶向代谢组学。DOR组肠道菌群健康指数更低、失调指数更高，Hoylesella属显著减少，且其丰度与AMH及AFC正相关；鉴定243个差异代谢物，其中硬脂酸对DOR区分AUC达0.89，网络药理学提示PI3K-Akt通路及五个核心靶点可能介导关联。研究提示“肠-卵巢轴”参与DOR，但机制尚缺实验验证。","summary":"STUDY QUESTION: Are there distinct variations in the gut microbiome and metabolism among infertile women diagnosed with diminished ovarian reserve (DOR), and how might the gut microbiome influence ovarian function? SUMMARY ANSWER: In DOR patients, Hoylesella abundance correlated with anti-Müllerian hormone (AMH)/antral follicle count (AFC), and stearic acid was identified as a key differential metabolite that was associated with activated PI3K-Akt signaling. WHAT IS KNOWN ALREADY: Accumulating evidence underscores the presence of a 'gut-ovary axis', highlighting a substantial interplay between the intestinal microbiome and ovarian function. However, the specific microbial and metabolic profiles characterizing infertile individuals with DOR remain largely uncharacterized. STUDY DESIGN, SIZE, DURATION: This study was a cross-sectional observational study. We enrolled participants receiving frozen embryo transfer at the First Affiliated Hospital of Zhengzhou University between 1 October 2024, and 31 December 2025. Each participant was limited to a single frozen embryo transfer within the study. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 190 participants were included: 91 with DOR and 99 with normal ovarian reserve (NOR). Clinical information and stool specimens were collected from every subject. Sequencing of 16S rRNA and non-targeted metabolomics were implemented to characterize the gut microbiome and metabolome, respectively. Molecular docking analysis and network pharmacology were then implemented to screen for overlapping genetic targets among DOR-associated targets and key metabolite-targeted proteins. MAIN RESULTS AND THE ROLE OF CHANCE: Relative to NOR controls, the DOR population exhibited significantly lower Gut Microbiota Health Index (P = 2.52 × 10-22) and higher Microbiota Dysbiosis Index (P = 8.31 × 10-10). The genus Hoylesella was significantly depleted in the DOR group (P = 0.018). Spearman analysis demonstrated that Hoylesella proportions were significantly positively correlated with AMH and AFC levels. Metabolomics analysis identified 243 differential metabolites across the study cohorts. Among these, four metabolites were associated with Hoylesella, and stearic acid exhibited high predictive performance (area under the curve = 0.89) for distinguishing DOR. Network pharmacology analysis of stearic acid and DOR identified five core targets: tumor necrosis factor, AKT serine/threonine kinase 1, SRC proto-oncogene, non-receptor tyrosine kinase (SRC), peroxisome proliferator-activated receptor gamma (PPARG), and epidermal growth factor receptor. Kyoto Encyclopedia of Genes and Genomes pathway enrichment indicated that the PI3K-Akt signaling pathway was the most significantly enriched. LARGE SCALE DATA: Raw 16S rRNA sequencing data have been deposited in the NCBI Sequence Read Archive under BioProject accession PRJNA1444490. Untargeted metabolomics data have been deposited in MetaboLights under accession MTBLS14194. LIMITATIONS, REASONS FOR CAUTION: The current investigation represents an initial effort to identify the alterations in intestinal microbes and associated metabolites in women with DOR-related infertility through 16S rRNA sequencing and untargeted metabolomics; however, experimental validation of the underlying mechanisms is still missing. Furthermore, the metabolomics analysis in this study did not further stratify by age. WIDER IMPLICATIONS OF THE FINDINGS: Through immunological dysregulation and inflammatory reactions, aberrant alterations in key intestinal microbes and metabolic products likely participate in the underlying mechanisms of DOR. These results provide direction for further research into the causal connections between important microbial species and metabolites in patients with DOR. FUNDING: This research was supported by grant 32271169 from the National Natural Science Foundation of China and the Henan Province Young and Middle-aged Health Science and Technology Innovation Leading Talent Project (Grant No. LJRC2024009). DISCLOSURES: The authors have no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.","interpretation_basis":null,"fulltext_status":null,"interpretation":null,"fulltext":{"available":false,"status":null,"reason":"尚未抓取全文（未入选、分数未达阈值，或还没跑 fulltext 步骤）","pmcid":null,"license":null,"chars":0,"source":null,"fetched_at":null}}