Dataset Information

Breast tissue, oral and urinary microbiomes in breast cancer.

ABSTRACT: It has long been proposed that the gut microbiome contributes to breast carcinogenesis by modifying systemic estrogen levels. This is often cited as a possible mechanism linking breast cancer and high-fat, low-fiber diets as well as antibiotic exposure, associations previously identified in population-based studies. More recently, a distinct microbiome has been identified within breast milk and tissue, but few studies have characterized differences in the breast tissue microbiota of patients with and without cancer, and none have investigated distant body-site microbiomes outside of the gut. We hypothesize that cancerous breast tissue is associated with a microbiomic profile distinct from that of benign breast tissue, and that microbiomes of more distant sites, the oral cavity and urinary tract, will reflect dysbiosis as well. Fifty-seven women with invasive breast cancer undergoing mastectomy and 21 healthy women undergoing cosmetic breast surgery were enrolled. The bacterial 16S rRNA gene was amplified from urine, oral rinse and surgically collected breast tissue, sequenced, and processed through a QIIME-based bioinformatics pipeline. Cancer patient breast tissue microbiomes clustered significantly differently from non-cancer patients (p=0.03), largely driven by decreased relative abundance of Methylobacterium in cancer patients (median 0.10 vs. 0.24, p=0.03). There were no significant differences in oral rinse samples. Differences in urinary microbiomes were largely explained by menopausal status, with peri/postmenopausal women showing decreased levels of Lactobacillus. Independent of menopausal status, however, cancer patients had increased levels of gram-positive organisms including Corynebacterium (p<0.01), Staphylococcus (p=0.02), Actinomyces (p<0.01), and Propionibacteriaceae (p<0.01). Our observations suggest that the local breast microbiota differ in patients with and without breast cancer. Cancer patient urinary microbiomes were characterized by increased levels of gram-positive organisms in this study, but need to be further studied in larger cohorts.

SUBMITTER: Wang H

PROVIDER: S-EPMC5675698 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Breast tissue, oral and urinary microbiomes in breast cancer.

Wang Hannah H Altemus Jessica J Niazi Farshad F Green Holly H Calhoun Benjamin C BC Sturgis Charles C Grobmyer Stephen R SR Eng Charis C

Oncotarget 20170814 50

It has long been proposed that the gut microbiome contributes to breast carcinogenesis by modifying systemic estrogen levels. This is often cited as a possible mechanism linking breast cancer and high-fat, low-fiber diets as well as antibiotic exposure, associations previously identified in population-based studies. More recently, a distinct microbiome has been identified within breast milk and tissue, but few studies have characterized differences in the breast tissue microbiota of patients wit ...[more]

PMID: 29152146

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Project description:BackgroundAlthough the vaginal and urinary microbiomes have been increasingly well-characterized in health and disease, few have described the relationship between these neighboring environments. Elucidating this relationship has implications for understanding how manipulation of the vaginal microbiome may affect the urinary microbiome and treatment of common urinary conditions.ObjectiveTo describe the relationship between urinary and vaginal microbiomes using 16S rRNA gene sequencing. We hypothesized that the composition of the urinary and vaginal microbiomes would be significantly associated, with similarities in predominant taxa.Study designThis multicenter study collected vaginal swabs and catheterized urine samples from 186 women with mixed urinary incontinence enrolled in a parent study and 84 similarly aged controls. Investigators decided a priori that if vaginal and/or urinary microbiomes differed between continent and incontinent women, the groups would be analyzed separately; if similar, samples from continent and incontinent women would be pooled and analyzed together. A central laboratory sequenced variable regions 1-3 (v1-3) and characterized bacteria to the genus level. Operational taxonomic unit abundance was described for paired vaginal and urine samples. Pearson's correlation characterized the relationship between individual operational taxonomic units of paired samples. Canonical correlation analysis evaluated the association between clinical variables (including mixed urinary incontinence and control status) and vaginal and urinary operational taxonomic units, using the Canonical correlation analysis function in the Vegan package (R version 3.5). Linear discriminant analysis effect size was used to find taxa that discriminated between vaginal and urinary samples.ResultsUrinary and vaginal samples were collected from 212 women (mean age 53±11 years) and results from 197 paired samples were available for analysis. As operational taxonomic units in mixed urinary incontinence and control samples were related in canonical correlation analysis and since taxa did not discriminate between mixed urinary incontinence or controls in either vagina or urine, mixed urinary incontinence and control samples were pooled for further analysis. Canonical correlation analysis of vaginal and urinary samples indicated that that 60 of the 100 most abundant operational taxonomic units in the samples largely overlapped. Lactobacillus was the most abundant genus in both urine and vagina (contributing on average 53% to an individual's urine sample and 64% to an individual's vaginal sample) (Pearson correlation r=0.53). Although less abundant than Lactobacillus, other bacteria with high Pearson correlation coefficients also commonly found in vagina and urine included: Gardnerella (r=0.70), Prevotella (r=0.64), and Ureaplasma (r=0.50). Linear discriminant analysis effect size analysis identified Tepidimonas and Flavobacterium as bacteria that distinguished the urinary environment for both mixed urinary incontinence and controls as these bacteria were absent in the vagina (Tepidimonas effect size 2.38, P<.001, Flavobacterium effect size 2.15, P<.001). Although Lactobacillus was the most abundant bacteria in both urine and vagina, it was more abundant in the vagina (linear discriminant analysis effect size effect size 2.72, P<.001).ConclusionSignificant associations between vaginal and urinary microbiomes were demonstrated, with Lactobacillus being predominant in both urine and vagina. Abundance of other bacteria also correlated highly between the vagina and urine. This inter-relatedness has implications for studying manipulation of the urogenital microbiome in treating conditions such as urgency urinary incontinence and urinary tract infections.

Project description:Aim: The gut microbiome plays a crucial role in colorectal cancer (CRC) tumorigenesis, but compositions of microorganisms have been inconsistent in previous studies due to the different types of specimens. We investigated the microbiomes and resistomes of CRC patients with colonic biopsy tissue and intestinal lavage fluid (IVF). Methods: Paired samples (biopsy tissue and IVF) were collected from 20 patients with CRC, and their gut microbiomes and resistomes were measured by shotgun metagenomics. Clinical and laboratory data were recorded. Bioinformatics (KneadData, Kraken2, and FMAP) and statistical analysis were done using the R (v4.0.2) software. Results: Bacterial diversity in IVF was higher than in tissue samples, and bacterial operational taxonomic units (OTUs) were 2,757 in IVF vs. 197 in tissue. β-diversity showed distinct clusters in paired samples. The predominant bacteria in IVF were phylum Proteobacteria, while the predominant bacteria of tissue were phylum Actinobacteria. Twenty-seven representative bacteria were selected to form six bacterial clusters, which showed only Firmicutes Cluster 1, and the Bacteroidetes Cluster 1 were significantly more abundant in the IVF group than those in the tissue group (p < 0.05). The Firmicutes Cluster 2, Bacteroidetes Cluster 2, Pathogen Cluster, and Prevotella Cluster were not significantly different between IVF and tissue (p > 0.05). Correlation analysis revealed that some bacteria could have effects on metabolic and inflammatory parameters of CRC patients. A total of 1,295 antibiotic resistance genes (ARGs) were detected in the gut microbiomes, which conferred multidrug resistance, as well as resistance to tetracycline, aminoglycoside, and more. Co-occurrence patterns revealed by the network showed mainly ARG-carrying bacteria to be similar between IVF and tissue, but leading bacteria located in the hub differed between IVF and tissue. Conclusion: Heterogeneity of microbiota is particularly evident when studied with IVF and tissue samples, but bacterial clusters that have close relationships with CRC carcinogenesis are not significantly different, using IVF as an alternative to tissue for gut microbiome, and resistome assessment may be a feasible method.

Project description:BackgroundPhthalates, known endocrine disruptors, may play a role in breast carcinogenesis. Few studies have examined phthalates in relation to breast cancer (BC), and, to our knowledge, none have considered survival following BC.ObjectivesWe examined 11 urinary phthalate metabolites, individually and as molar sum groupings, in association with BC incidence and subsequent survival.MethodsOur study includes 710 women diagnosed with first primary BC in 1996-1997 and 598 women without BC from Long Island, New York. Within 3 mo of diagnosis, participants provided spot urine samples. Nine phthalate metabolites were measured in all women; two [monocarboxyoctyl phthalate (MCOP) and monocarboxy-isononyl phthalate (MCNP)] were measured in 320 women with and 205 without BC. Women with BC were followed since diagnosis using the National Death Index; during follow-up (median=17.6 y), we identified 271 deaths (98 BC related). We examined creatinine-corrected metabolite concentrations in association with: BC, using logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) and all-cause/BC-specific mortality, using Cox regression to estimate hazard ratios (HRs) and 95% CIs. We also examined effect modification by body mass index (BMI) and estrogen receptor (ER) status.ResultsThe highest (vs. lowest) quintiles of mono(3-carboxypropyl) phthalate (MCPP), monobenzyl phthalate (MBzP), MCNP, and MCOP were associated with BC ORs ranging from 0.71-0.73. The highest (vs. lowest) quintiles of mono(2-ethylhexyl) phthalate (MEHP) and MCOP were associated with BC-specific mortality HRs of 0.54 (95% CI: 0.28, 1.04) and 0.55 (95% CI: 0.23, 1.35), respectively. For BC-specific mortality, interactions were significant between BMI and mono(2-ethyl-5-oxyhexyl) phthalate (MEOHP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), and mono(2-ethyl-5-carboxypentyl) phthalate (MECPP), with positive associations among women with BMI<25 and inverse associations among women with BMI≥25.0 kg/m2.ConclusionsConsistent with laboratory evidence, we observed inverse associations between urinary concentrations of several phthalate metabolites and BC and subsequent survival; however, these results should be interpreted with caution given that biospecimen collection among women with BC occurred after diagnosis, which may be of particular concern for our case-control findings. https://doi.org/10.1289/EHP2083.

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Breast tissue, oral and urinary microbiomes in breast cancer.

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Breast tissue, oral and urinary microbiomes in breast cancer.

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