Huan Yi

Long-term outcomes after unilateral salpingo-oophorectomy: A registry-based retrospective cohort study

Background Opportunistic bilateral salpingo-oophorectomy (BSO) is recommended in women who have undergone a hysterectomy due to gynecological carcinomas and/or in women with genetic indications, especially for women who do not intend to conceive. However, there is ongoing debate about whether BSO should be recommended in premenopausal women, due to the early cessation of estradiol because of BSO which is linked to several health concerns, including coronary artery disease (CAD) and osteoporosis. This study aims to explore whether ovarian cancer can be prevented by unilateral salpingo-oophorectomy (USO) while not affecting the long-term risk of CAD and osteoporosis. Methods and findings By accessing the Swedish national registries, this retrospective cohort study included 42,306 women who underwent USO between 1993 and 2018 before the age of 50 years. These women were randomly matched with 211,530 women who had not undergone USO using a propensity score matching approach to ensure comparability between the groups. Follow-up started on the date of USO operation and continued until the earliest occurrence of the following events: diagnosis of specific outcomes of interest, death from any cause, or the end of the study period (31st December 2018). Cox regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) of overall and histology-specific ovarian cancer, CAD, and osteoporosis associated with USO. After a median follow-up of 13 years, our analyses revealed that USO was not associated with subsequent risk of CAD (HR = 1.02, 95% CI [0.95, 1.09]) and osteoporosis (HR = 1.06, 95% CI [0.98, 1.16]). However, USO was significantly associated with a reduced risk of high-grade serous ovarian carcinoma (HR = 0.64, 95% CI [0.45, 0.92]). No differences were found when the analyses were stratified by hysterectomy. The main limitation of the study was that some confounding factors, such as BRCA1/2 pathological mutant status, were not available in our database. Conclusions Our study suggests that USO reduces the risk of HGSCs but was not associated with CAD or osteoporosis after a median 13-year follow-up. These results suggest that USO may be a safer option than BSO for lowering ovarian cancer risk in premenopausal women, as it could avoid the negative health effects of early menopause.

Mannose Enhances Immunotherapy Efficacy in Ovarian Cancer by Modulating Gut Microbial Metabolites

Abstract The gut microbiome significantly influences the effectiveness of immune checkpoint blockade therapy. However, its clinical application is hindered by the absence of cost-effective production methods. In this study, we demonstrated that oral mannose supplementation inhibits ovarian tumor growth in immunocompetent mice through the enrichment of Faecalibaculum rodentium (F. rodentium). Administration of F. rodentium not only suppressed tumor progression but also enhanced antitumor immune responses. Mannose supplementation fostered an immune stimulatory tumor microenvironment, characterized by the expansion and differentiation of progenitor-exhausted CD8+ T cells (Tpex). Metabolomics analysis identified propionate and butyrate as critical metabolites driving the mannose-mediated tumor-suppressive effects, which was validated in vivo. Mechanistically, propionate and butyrate enhanced histone acetylation to promote Tpex-cell expansion. Moreover, a mannose-related gene signature was associated with favorable response to immune checkpoint blockade therapy across multiple cancer types. Supplementation with mannose also improved the efficacy of anti–PD-1 therapy and PARP inhibitor treatment. These findings highlight the role of F. rodentium–derived metabolites propionate and butyrate as key stimulators of Tpex-cell expansion, thereby activating antitumor immune responses. This underscores the therapeutic potential of mannose supplementation in enhancing cancer immunotherapy outcomes in high-grade serous ovarian cancer. Significance: Alterations to the gut microbiome induced by mannose engender an immune stimulatory tumor microenvironment responsive to immunotherapy, suggesting that mannose may be an effective and safe adjuvant therapy for stimulating immunotherapy sensitivity.

The Role of Gut Microbiota and Their Derived Metabolites in Chemotherapy‐Induced Nausea and Vomiting in Ovarian Cancer

ABSTRACT Objective This study aimed to investigate the relationship between gut microbiota and chemotherapy‐induced nausea and vomiting (CINV) in patients with ovarian cancer undergoing platinum‐based chemotherapy (carboplatin or cisplatin combined with paclitaxel). Methods Clinical data and fecal samples were collected from patients with ovarian cancer after admission but prior to the initiation of their first chemotherapy cycle. Patients were divided into the CINV ( n  = 25) and non‐CINV ( n  = 25) groups on the basis of symptoms occurring after chemotherapy. No additional samples were collected during chemotherapy. Integrated metagenomic sequencing and untargeted metabolomic profiling identified CINV‐associated microbial taxa and metabolites. Additionally, fecal microbiota transplantation (FMT) in SD rats validated causal links between gut dysbiosis and CINV pathogenesis. Results Bacteroides caccae , Corynebacteriales, and Corynebacterium were significantly enriched in the CINV group. KEGG enrichment revealed upregulated pathways in CINV, including focal adhesion, lysosome function, and eukaryotic cellular communities. Metabolomic analysis identified 19 significantly increased metabolites in the fecal samples of CINV patients versus 10 in non‐CINV controls. KEGG enrichment revealed that the pentose phosphate pathway, glutathione metabolism, and lipoic acid metabolism were significantly implicated in CINV pathogenesis. Multi‐omics integration revealed Bacteroides sp. A1C1 strongly correlated with hesperetin, arbutin, orciprenaline, and myristolic acid. In rats, cisplatin‐induced CINV models showed higher kaolin consumption versus controls ( p  < 0.05). FMT from non‐CINV donors reduced kaolin consumption in cisplatin‐treated rats ( p  < 0.05). The expression of 5‐HT3R, NK1R, and NK2R in the medulla oblongata and colon was significantly increased in the cisplatin model group ( p  < 0.05) and partially reversed by non‐CINV FMT ( p  < 0.05). Conclusions Gut microbiota dysbiosis directly contributes to CINV pathogenesis. Bacteroides sp. A1C1 and its putatively identified metabolites (hesperetin, arbutin, orciprenaline, and myristolic acid) represent potential diagnostic biomarkers for CINV.