In recent years, cancer has become the leading cause of death in urban areas and the second leading cause of death in rural areas. Incidence and mortality rates of gynecological tumors are on the rise and pose a threat to women's health. Among these tumors, UF are the most common. CC, EC, and OC are the three most common gynecologic malignancies and rank in the top 10 in female cancer incidence. [1]. The occurrence of gynecological tumors is influenced by a variety of factors, including genetics, hormonal imbalances, obesity, persistent HPV infection, and chronic conditions such as endometriosis.
The human microbiome is the microbiome that resides in specific areas of the body [2]. It plays a vital role in maintaining organismal balance and host health. It possesses many important functions, such as nutrient absorption, maintaining the integrity of epithelial barrier, removing harmful substances, regulating inflammation and immune response, and protecting against pathogen invasion [3]. In recent years, with the development of next-generation sequencing technologies, we have gained a deeper understanding of the diversity of the human microbiome. Among them, the gut microbiome is widely studied. The normal gut microbiome consists mainly of the phyla Bacteroidetes and Firmicutes [4]. The dominant microbiota in the gut of healthy individuals produces short-chain fatty acids by fermenting carbohydrates, proteins and peptides. These SCFAs help maintain an acidic gut environment, promote the growth of beneficial bacteria and inhibit the colonization of potential pathogens. In addition, SCFA helps maintain gut barrier function, stimulates intestinal epithelial cell regeneration, and promotes the production of antimicrobial peptides and mucus. In summary, a healthy gut microbiome plays an important role in suppressing chronic inflammation, obesity, metabolic syndrome and cancer-related diseases[5].
Microbial communities exists in a symbiotically balanced manner within the host.However, several factors can influence the composition of the microbiome, such as medication, obesity, diet, exercise, race, geography, and genetics [5]. Intestinal dysbiosis refers to a decline in diversity and stability of the gut microbiota, leading to the overgrowth of opportunistic pathogens and the production of specific bacterial by-products, and immunological and metabolic disturbances. Studies have linked intestinal dysbiosis to inflammatory bowel disease, diabetes, obesity, metabolic syndrome, cancer, and more [5]. Recently, the relationship between gut microbiota and tumors has become a hot topic. Previous studies have confirmed the role of microbial dysbiosis in gastrointestinal tumors, such as colorectal and liver cancer. In addition to the digestive tract, the gut microbiota is also associated with skin, mouth, lung and reproductive cancers [7]. The mechanisms by which microbes drive cancer are multifaceted. In gynecological tumors, intestinal dysbiosis, in addition to regulating inflammatory responses, plays a critical role in gynecological tumors through DNA damage, effects on estrogen levels, and production of toxins and metabolites associated with gut bacteria[8].
The gut microbiome affects the carcinogenesis of gynecological tumors. By comparing the differences in gut microbiota composition between UF patients and healthy individuals, we found a decrease in the abundance of Bifidobacteria scardovii, Ligilactobacillus saerimneri, and Lactococcus raffinolactis, while the abundance of Pseudomonas stutzeri and Prevotella amnii were increased [9]. Zq Wang et al.'s study, using 16S rRNA sequencing analysis, showed a significant increase in the abundance of Proteobacteria in the gut microbiota of CC patients compared to the control, while the abundance of Firmicutes was relatively reduced [10]. After adjusting for age and race, Prevotella, Porphyromonas, and Dialister were significantly enriched, while Bacteroides, Alistipes, and Lachnospiracea were decreased in CC[11]. Ss Zhao et al. Identified the differences in gut microbiota between EC patients and healthy individuals. The study found Ruminococcus were enriched in EC and could serve as prognostic biomarkers, providing new targets for clinical treatment [12]. Some bacterial metabolites also impact the development of EC: butyrate exhibits anti-inflammatory and anti-tumor effects, while the overexpression of tryptophan decarboxylase is associated with poor prognosis in EC [13]. Proteobacteria and Veillonella were more abundant among breast cancer and ovarian cancer patients with cachexia [14]. Chambers et al.'s study demonstrated that dysbiosis of the gut microbiota in OC can lead to tumor progression and resistance to cisplatin chemotherapy [15].
However, these findings are mainly based on cross-sectional studies and cannot determine causation. Establishing causality can improve our understanding of gynecological tumor development mechanisms and potentially guide the development of microbial interventions. Therefore, elucidating the causal relationship between gut microbiota and gynecological tumors is critical. Mendelian randomization explores causal relationships between risk factors and outcomes, often unaffected by confounding and reverse causality, by integrating aggregated data from GWAS and using genetic variation as IVs [16]. Hence, the purpose of this study is to explore the causal relationship between gut microbiota and gynecological tumors and to provide a theoretical basis for the development of potential therapeutic targets for gynecological tumors.