Comprehensive profiles and diagnostic value of menopausal-specific gut microbiota in premenopausal breast cancer

Abstract

In Western countries, breast cancer tends to occur in older postmenopausal women. However, in Asian countries, the proportion of younger premenopausal breast cancer patients is increasing. Increasing evidence suggests that the gut microbiota plays a critical role in breast cancer. However, studies on the gut microbiota in the context of breast cancer have mainly focused on postmenopausal breast cancer. Little is known about the gut microbiota in the context of premenopausal breast cancer. This study aimed to comprehensively explore the gut microbial profiles, diagnostic value, and functional pathways in premenopausal breast cancer patients. Here, we analyzed 267 breast cancer patients with different menopausal statuses and age-matched female controls. The α-diversity was significantly reduced in premenopausal breast cancer patients, and the β-diversity differed significantly between breast cancer patients and controls. By performing multiple analyses and classification, 14 microbial markers were identified in the different menopausal statuses of breast cancer. Bacteroides fragilis was specifically found in young women of premenopausal statuses and Klebsiella pneumoniae in older women of postmenopausal statuses. In addition, menopausal-specific microbial markers could exhibit excellent discriminatory ability in distinguishing breast cancer patients from controls. Finally, the functional pathways differed between breast cancer patients and controls. Our findings provide the first evidence that the gut microbiota in premenopausal breast cancer patients differs from that in postmenopausal breast cancer patients and shed light on menopausal-specific microbial markers for diagnosis and investigation, ultimately providing a noninvasive approach for breast cancer detection and a novel strategy for preventing premenopausal breast cancer.

The involvement of oncobiosis and bacterial metabolite signaling in metastasis formation in breast cancer

“…Multiple microbial compartments undergo oncobiotic transformation during breast cancer, including breast tissue [55,56], milk ducts [57], the inherent microbiome of the breast carcinoma [54,[58][59][60][61][62][63][64][65][66][67][68][69][70][71][72], the distal gut [51,52,[73][74][75][76][77][78][79][80][81][82][83][84][85][86][87][88][89], and the urinary microbiome [54,90]. However, no differences in the microbiome of the nipple [57,69] and the oral microbiome [54] between healthy individuals and breast cancer patients have been detected.…”

“…Ubiquinone biosynthesis Jasmonic acid biosynthesis Beta oxidation LPS biosynthesis Glyoxylate cycle [75] Meta cleavage pathway of aromatic compounds Aromatic biogenic amine degradation Androstenedione degradation [87] LPS biosynthesis Ubiquinone and other terpenoid-quinone biosynthesis Folate biosynthesis Aminobenzoate degradation Biotin metabolism Glutathione metabolism Penicillin and cephalosporin biosynthesis D-Arginine and D-ornithine metabolism N-glycan biosynthesis Isoquinoline alkaloid biosynthesis Styrene degradation TCA cycle Geraniol degradation Indole alkaloid biosynthesis Glycolysis/gluconeogenesis Glycerophospholipid metabolism [89] with the receptor status, grade, and stage. The intratumoral expression of AHR, PXR, and TGR5 decreases in TNBC cases compared to ER + cases [81,97].…”

“…Alpha diversity increased in patients [ 84 ] 200 BC patients (stages I–II) and 67 controls 16S rRNA gene sequencing Alpha diversity lower in premenopausal patients, no difference in the postmenopausal cohort; beta diversity is different. Bacteroidetes proportions increased in BC patients [ 87 ] 76 BC patients (35 stage II/III, 21 stage I), 336 healthy volunteers Comprehensive shotgun sequencing 52 units, mostly at the species level, decreased, while 38 units increased in breast cancer patients compared to healthy volunteers. 11 species increased in stage II/III patients, while 21 species increased in stage I patients [ 86 ] 83 invasive BC patients, 19 patients with benign breast tumors 16S rRNA gene sequencing No difference in alpha and beta diversity indices.…”

“…Howe and co-workers [ 76 ] reported increases in alpha diversity indices in a Pten-deficient mouse model backing the observations of Zhu and colleagues [ 75 ] and Bobin-Dubigeon and co-workers [ 84 ]. No differences in alpha diversity were reported in [ 87 ] and [ 89 ]. However, the multiple observations make lower alpha diversity more likely.…”

“…Our current understanding indicates that these metabolites only represent the tip of the iceberg. Multiple studies [ 75 , 87 , 89 ] identified imputed pathways that were differentially regulated in the oncobiome and eubiome in breast cancer patients (Table 5 ). In addition to the metabolic changes, a large set of transport systems are dysregulated in bacteria [ 75 ].…”