Akkermansia supplementation reverses the tumor-promoting effect of the fecal microbiota transplantation in ovarian cancer.

Ovarian cancer (OC) remains a clinical challenge for its difficulty in early diagnosis and insensitivity to treatments. Gut microbiota modulate multiple carcinoma progression through immunoregulation. The relationship between OC and gut microbiota has not been fully characterized. We find that the feces of patients with OC demonstrate different characteristics from benign controls. After fecal microbiota transplantation (FMT) from patients with OC into OC-bearing mice, the tumor development accelerates. Further, an Akkermansia supplementation with FMT significantly suppresses OC progression in mice. RNA sequencing of tumors shows that T cell activation pathways are upregulated after Akkermansia supplementation with FMT. Moreover, acetate accumulation accompanies Akkermansia abundance elevation, which is associated with enhanced interferon γ (IFNγ) secretion of CD8+ T cells and also its tumor-killing property. This work highlights the importance of protective gut microbiome in immune surveillance of OC, which connects accumulation of acetate and the cytotoxic function of CD8+ T cells by increasing IFNγ secretion.

Melatonin provides protection against cisplatin-induced ovarian damage and loss of fertility in mice.

RESEARCH QUESTION: Can melatonin provide non-invasive ovarian protection against damage caused by cis-diamminedichloroplatinum (cisplatin) and preserve fertility in female cancer patients? And if so, what is the possible mechanism? DESIGN: Athymic BALB/c nude tumour-bearing female mice were used to demonstrate whether melatonin affects the antineoplastic effect when co-administrated with cisplatin. Sexually mature and newborn C57BL/6 female mice were used to evaluate the potential effects of melatonin on the ovarian follicle pool, pregnancy rate and litter number in cisplatin-treated mice. The ovaries underwent immunohistochemical, TdT (terminal deoxynucleotidyl transferase)-mediated dUTP nick-end labelling (TUNEL) and gene array analysis to explore the underlying mechanism. In addition, granulosa cells were isolated to investigate the potential protective mechanism of melatonin. RESULTS: Melatonin not only enhanced the anti-cancer effect of cisplatin in tumour-bearing nude mice, but also reduced ovarian toxicity and preserved long-term fertility in cisplatin-treated C57BL/6 female mice. When co-administrated, melatonin was able to reduce the DNA damage and toxic effects on lipid peroxidation in the ovaries caused by cisplatin. Specifically, melatonin was able to largely restore lipid peroxidation in granulosa cells and thus prevent ovarian follicles from being depleted. CONCLUSIONS: Melatonin has the potential to be used as a chemotherapeutic adjuvant to simultaneously improve the outcome of anti-cancer treatment and preserve ovarian function during cisplatin chemotherapy. Notably, its properties of DNA protection and antioxidant effects on follicles may benefit female cancer survivors and prevent premature ovarian failure as well as fertility loss caused by chemotherapy.