Gut Microbiota Dynamics during Chemotherapy in Epithelial Ovarian Cancer Patients Are Related to Therapeutic Outcome

Abstract

Epithelial ovarian cancer (EOC) is one of the most lethal and silent gynecological tumors. Despite appropriate surgery and chemotherapy, relapse occurs in over half of patients with a poor prognosis. Recently, the gut microbiota (GM) was hypothesized to influence the efficacy of anticancer therapies, but no data are available in EOC. Here, by 16S rRNA gene sequencing and inferred metagenomics, we profiled the GM of EOC patients at diagnosis and reconstructed its trajectory along the course of neoadjuvant or adjuvant chemotherapy up to follow-up. Compared to healthy subjects, the GM of EOC patients appeared unbalanced and severely affected by chemotherapy. Strikingly, discriminating patterns were identified in relation to the therapeutic response. Platinum-resistant patients showed a marked temporal reduction in GM diversity and increased instability with loss of health-associated taxa and increased proportions of Coriobacteriaceae and Bifidobacterium. Notably, most of these microorganisms are lactate producers, suggesting increased lactate production as supported by inferred metagenomics. In contrast, the GM of platinum-sensitive patients appeared overall more diverse and stable and enriched in lactate utilizers from the Veillonellaceae family. In conclusion, we identified potential GM signatures of therapeutic outcome in EOC patients, which could open up new opportunities for cancer prognosis and treatment.

Analysis of microbiome in gastrointestinal stromal tumors: Looking for different players in tumorigenesis and novel therapeutic options

“…Indeed, several reports show that alpha diversity is usually higher in normal tissues and benign lesions when compared with tumor. 35 , 36 , 37 , 38 Moreover, higher alpha diversity is often associated with prolonged overall survival in cancer patients 39 , 40 , 41 , 42 ; however, we did not observe significant differences between LR and HR/MET GISTs, which generally show shorter overall survival. 43 …”

Gut Microbiota Characteristics Are Associated With Severity of Acute Radiation-Induced Esophagitis

“…We found that patients in the mild ARIE subgroup had significantly higher abundances of Roseburia , Veillonella , Prevotella_9 , Megasphaera , and Ruminococcus_2 , genera associated with the production of short-chain fatty acids (SCFAs) ( de la Cuesta-Zuluaga et al, 2017 ; Louis and Flint, 2017 ; D’Amico et al, 2021 ), including butyrate, propionate, and acetate. Many studies have examined butyrate due to its anti-inflammatory and anti-cancer effects.…”

Gut Microbes in Gynecologic Cancers: Causes or Biomarkers and Therapeutic Potential

“…This means that an imbalance in GM diminishes the original protective effect and promotes the development of colorectal cancer ( 14 ). Also, GM may affect the efficacy of drugs during cancer treatment by targeting the immune response and disrupting the chemotherapeutic drug sensitivity ( 15 , 16 ). At present, immunotherapy for cancer is a major hot topic in cancer treatment.…”

“…The advert effects of chemotherapy on GM, e.g. dysbiosis, are more prevalent in patients ( 16 ) and animal ( 40 ) models bearing ovarian cancers. In addition, compared to platinum-sensitive patients, platinum-resistant patients showed a more pronounced dysbiosis of GM, with a decrease in the health-related groups and an increase in the proportion of lactic acid-producing bacteria including Coriobacteriaceae and Bifidobacterium ( 16 ).…”

“…dysbiosis, are more prevalent in patients ( 16 ) and animal ( 40 ) models bearing ovarian cancers. In addition, compared to platinum-sensitive patients, platinum-resistant patients showed a more pronounced dysbiosis of GM, with a decrease in the health-related groups and an increase in the proportion of lactic acid-producing bacteria including Coriobacteriaceae and Bifidobacterium ( 16 ). In addition to reduced platinum sensitivity, animal studies have revealed that the destruction of GM contributes to the growth of ovarian malignancies and reduces mice survival ( 41 ).…”