Gut microbial diversity and genus-level differences identified in cervical cancer patients versus healthy controls

Abstract

Objectives: The aim of this study was to characterize variation in the gut microbiome of women with locally advanced cervical cancer and compare it to healthy controls.

Methods: We characterized the 16S rDNA fecal microbiome in 42 cervical cancer patients and 46 healthy female controls. Shannon diversity index (SDI) was used to evaluate alpha (within sample) diversity. Beta (between sample) diversity was examined using principle coordinate analysis (PCoA) of unweighted Unifrac distances. Relative abundance of microbial taxa was compared between samples using Linear Discriminant Analysis Effect Size (LEfSe).

Results: Within cervical cancer patients, bacterial alpha diversity was positively correlated with age (p = 0.22) but exhibited an inverse relationship in control subjects (p < 0.01). Alpha diversity was significantly higher in cervical cancer patients as compared to controls (p < 0.05), though stratification by age suggested this relationship was restricted to older women (>50 years; p < 0.01). Beta diversity (unweighted Unifrac; p < 0.01) also significantly differed between cervical cancer patients and controls. Based on age- and race-adjusted LEfSe analysis, multiple taxa significantly differed between cervical cancer patients and controls. Prevotella, Porphyromonas, and Dialister were significantly enriched in cervical cancer patients, while Bacteroides, Alistipes and members of the Lachnospiracea family were significantly enriched in healthy subjects.

Conclusion: Our study suggests differences in gut microbiota diversity and composition between cervical cancer patients and controls. Associations within the gut microbiome by age may reflect etiologic/clinical differences. These findings provide rationale for further study of the gut microbiome in cervical cancer.

Keywords: Cervical cancer; Gut microbiota; Gynecologic cancer; Microbiome.

Figure 1.

The fecal microbiota of individuals with cervical cancer. The Shannon diversity index showed a trend to increase with age in cervical cancer subjects but did not reach statistical significance. B) Bacterial community composition does not vary between younger and older individuals with cervical cancer as determined by PCoA of the unweighted UniFrac distance. C) Stacked bar plot of the top 10 most abundant order-level bacteria in cervical cancer patients. Each bar represents a single participant and is labeled with subject age.

Figure 2.

The fecal microbiota of individuals with cervical cancer by demographics. Alpha diversity (within sample diversity) was measured using the Shannon diversity index and Beta diversity (between sample diversity) was determined by unweighted Unifrac. No differences were observed in either metric by race (A,D), histology (B,E) or cancer stage (C,F).

Figure 3.

The fecal microbiota of individuals with cervical cancer is statistically significantly different from that of healthy individuals. A) Overall alpha diversity, as assessed by Shannon diversity in cervical cancer patient’s vs. controls. B) Alpha diversity, as assessed by Shannon diversity in cervical cancer patient’s vs. controls stratified by age group. C) Shannon alpha-diversity index decreased with age in control subjects (p < 0.01). D,E) Beta diversity, as assessed by unweighted UniFrac, demonstrates significant compositional differences at the community level in cervical cancer patients vs. controls regardless of age.

Figure 4.

LEfSe analysis identified the most differentially abundant taxa between cervical cancer and healthy controls. A,B,C) Histogram of the linear discriminant analysis (LDA) scores unadjusted (A), and adjusted for age (B) and race (C) demonstrates significant compositional differences across a range of taxa in cervical cancer patients (green) vs. controls (red). LEfSe was restricted to p < 0.05 for class and subclass analysis and a minimum LDA score of 3.0.