Gut Microbiome Associations With Depressive Symptoms in Women With Gynecologic Cancer: A Longitudinal Study

Abstract

About one-quarter of women diagnosed with gynecologic cancer experience depressive symptoms. While the precise mechanism remains unclear, little is known about the association between gut microbiota and depressive symptoms in gynecologic cancer. Thus, this study aimed to evaluate the associations between gut microbiota and depressive symptoms in women with gynecologic cancer over cancer treatment. Thirty-seven women with cervical or endometrial cancer were followed at pre-treatment (T0), 6–8 weeks (T1), and 6 months post-radiation (T2). Depressive symptoms were assessed using the Patient Health Questionnaire-9 (PHQ-9). Rectal swabs were collected at each visit and sequenced for the V4 region of the 16S rRNA gene. MaAsLin2 models evaluated cross-sectional associations between gut microbial taxa and depressive symptoms at each time point, whereas GEE models assessed longitudinal associations over the course of cancer treatment. The patients had an average age of 60 years, and 43% were Black. At baseline (T0), 24% of patients exhibited depressive symptoms, which decreased to 21% at T1 and further to 13% at T2. GEE models showed that lower α-diversity (Shannon index, p = 0.05), dissimilar β-diversity (Bray-Curtis distance, p = 0.02), and reduced abundance of the genus Ruminococcus (p = 0.02) were predictive factors associated with depressive symptoms throughout cancer treatment. Higher depressive symptoms were longitudinally associated with lower gut microbial Shannon diversity, dissimilar microbial community composition, and lower abundance of the genus Ruminococcus. Larger longitudinal studies using shotgun metagenomic sequencing are needed to validate these findings and further elucidate the microbial mechanisms underlying depressive symptoms in women with gynecologic cancers.