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Abstract
BackgroundIncreasing evidence suggests that gut microbiota play a role in the pathogenesis of breast cancer. The composition and functional capacity of gut microbiota associated with breast cancer have not been studied systematically.MethodsWe performed a comprehensive shotgun metagenomic analysis of 18 premenopausal breast cancer patients, 25 premenopausal healthy controls, 44 postmenopausal breast cancer patients, and 46 postmenopausal healthy controls.ResultsMicrobial diversity was higher in breast cancer patients than in controls. Relative species abundance in gut microbiota did not differ significantly between premenopausal breast cancer patients and premenopausal controls. In contrast, relative abundance of 45 species differed significantly between postmenopausal patients and postmenopausal controls: 38 species were enriched in postmenopausal patients, including Escherichia coli, Klebsiella sp_1_1_55, Prevotella amnii, Enterococcus gallinarum, Actinomyces sp. HPA0247, Shewanella putrefaciens, and Erwinia amylovora, and 7 species were less abundant in postmenopausal patients, including Eubacterium eligens and Lactobacillus vaginalis. Acinetobacter radioresistens and Enterococcus gallinarum were positively but weakly associated with expression of high-sensitivity C-reactive protein; Shewanella putrefaciens and Erwinia amylovora were positively but weakly associated with estradiol levels. Actinomyces sp. HPA0247 negatively but weakly correlated with CD3+CD8+ T cell numbers. Further characterization of metagenome functional capacity indicated that the gut metagenomes of postmenopausal breast cancer patients were enriched in genes encoding lipopolysaccharide biosynthesis, iron complex transport system, PTS system, secretion system, and beta-oxidation.ConclusionThe composition and functions of the gut microbial community differ between postmenopausal breast cancer patients and healthy controls. The gut microbiota may regulate or respond to host immunity and metabolic balance. Thus, while cause and effect cannot be determined, there is a reproducible change in the microbiota of treatment-naive patients relative to matched controls.
Highlights
Increasing evidence suggests that gut microbiota play a role in the pathogenesis of breast cancer
Taxonomic characterization of gut microbiota in breast cancer patients and healthy controls A total of 133 stool samples were sequenced from premenopausal breast cancer patients (n = 18), premenopausal healthy controls (n = 25), postmenopausal breast cancer patients (n = 44), and postmenopausal healthy controls (n = 46)
The premenopausal breast cancer patients and controls were similar for age, BMI, and ethnicity (P > 0.05, Table 1); the postmenopausal breast cancer patients and controls were similar for age, BMI, age at menopause, and ethnicity (P > 0.05, Table 1)
Summary
Increasing evidence suggests that gut microbiota play a role in the pathogenesis of breast cancer. Increasing evidence suggests that microbe-host interactions have the potential to influence or serve as a biomarker of breast cancer pathogenesis [24, 25]. A comparison of 11 breast cancer patients and 7 healthy controls revealed differences in the gut microbiota, with Clostridia, Enterobacterium, Lactobacilli, Bacteroides, and Escherichia coli enriched in patients [24]. A comparison of 48 postmenopausal breast cancer case patients and 48 healthy controls [25] revealed an altered, less diverse gut microbiota in patients: Clostridiales, Clostridiaceae, Faecalibacterium, and Ruminococcaceae were enriched in patients, while Dorea and Lachnospiraceae were relatively less abundant in patients. Microbiota diversity correlated with total estrogen levels, suggesting that gut microbiota may be implicated in breast cancer by responding to or affecting estrogen metabolism
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