Elucidating the roles of the mammary and gut microbiomes in breast cancer development

The mammary microbiome is a newly characterized bacterial niche that might offer biological insight into the development of breast cancer. Together with in-depth analysis of the gut microbiome in breast cancer, current evidence using next-generation sequencing and metabolic profiling suggests compositional and functional shifts in microbial consortia are associated with breast cancer. In this review, we discuss the fundamental studies that have progressed this important area of research, focusing on the roles of both the mammary tissue microbiome and the gut microbiome. From the literature, we identified the following major conclusions, (I) There are unique breast and gut microbial signatures (both compositional and functional) that are associated with breast cancer, (II) breast and gut microbiome compositional and breast functional dysbiosis represent potential early events of breast tumor development, (III) specific breast and gut microbes confer host immune responses that can combat breast tumor development and progression, and (IV) chemotherapies alter the microbiome and thus maintenance of a eubiotic microbiome may be key in breast cancer treatment. As the field expectantly advances, it is necessary for the role of the microbiome to continue to be elucidated using multi-omic approaches and translational animal models in order to improve predictive, preventive, and therapeutic strategies for breast cancer

Composition and Functional Potential of the Human Mammary Microbiota Prior to and following Breast Tumor Diagnosis

Microbiota studies have reported changes in the microbial composition of the breast upon cancer development. However, results are inconsistent and limited to the later phases of cancer development (after diagnosis). We analyzed and compared the resident bacterial taxa of histologically normal breast tissue (healthy, H, n = 49) with those of tissues donated prior to (prediagnostic, PD, n = 15) and after (adjacent normal, AN, n = 49, and tumor, T, n = 46) breast cancer diagnosis (n total = 159). DNA was isolated from tissue samples and submitted for Illumina MiSeq paired-end sequencing of the V3-V4 region of the 16S gene. To infer bacterial function in breast cancer, we predicted the functional bacteriome from the 16S sequencing data using PICRUSt2. Bacterial compositional analysis revealed an intermediary taxonomic signature in the PD tissue relative to that of the H tissue, represented by shifts in Bacillaceae, Burkholderiaceae, Corynebacteriaceae, Streptococcaceae, and Staphylococcaceae. This compositional signature was enhanced in the AN and T tissues. We also identified significant metabolic reprogramming of the microbiota of the PD, AN, and T tissue compared with the H tissue. Further, preliminary correlation analysis between host transcriptome profiling and microbial taxa and genes in H and PD tissues identified altered associations between the human host and mammary microbiota in PD tissue compared with H tissue. These findings suggest that compositional shifts in bacterial abundance and metabolic reprogramming of the breast tissue microbiota are early events in breast cancer development that are potentially linked with cancer susceptibility

Associations between infant fungal and bacterial dysbiosis and childhood atopic wheeze in a nonindustrialized setting.

BACKGROUND: Asthma is the most prevalent chronic disease of childhood. Recently, we identified a critical window early in the life of both mice and Canadian infants during which gut microbial changes (dysbiosis) affect asthma development. Given geographic differences in human gut microbiota worldwide, we studied the effects of gut microbial dysbiosis on atopic wheeze in a population living in a distinct developing world environment. OBJECTIVE: We sought to determine whether microbial alterations in early infancy are associated with the development of atopic wheeze in a nonindustrialized setting. METHODS: We conducted a case-control study nested within a birth cohort from rural Ecuador in which we identified 27 children with atopic wheeze and 70 healthy control subjects at 5 years of age. We analyzed bacterial and eukaryotic gut microbiota in stool samples collected at 3 months of age using 16S and 18S sequencing. Bacterial metagenomes were predicted from 16S rRNA data by using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States and categorized by function with Kyoto Encyclopedia of Genes and Genomes ontology. Concentrations of fecal short-chain fatty acids were determined by using gas chromatography. RESULTS: As previously observed in Canadian infants, microbial dysbiosis at 3 months of age was associated with later development of atopic wheeze. However, the dysbiosis in Ecuadorian babies involved different bacterial taxa, was more pronounced, and also involved several fungal taxa. Predicted metagenomic analysis emphasized significant dysbiosis-associated differences in genes involved in carbohydrate and taurine metabolism. Levels of the fecal short-chain fatty acids acetate and caproate were reduced and increased, respectively, in the 3-month stool samples of children who went on to have atopic wheeze. CONCLUSIONS: Our findings support the importance of fungal and bacterial microbiota during the first 100 days of life on the development of atopic wheeze and provide additional support for considering modulation of the gut microbiome as a primary asthma prevention strategy

Asthma and the microbiome: defining the critical window in early life

Asthma is a chronic inflammatory immune disorder of the airways affecting one in ten children in westernized countries. The geographical disparity combined with a generational rise in prevalence, emphasizes that changing environmental exposures play a significant role in the etiology of this disease. The microflora hypothesis suggests that early life exposures are disrupting the composition of the microbiota and consequently, promoting immune dysregulation in the form of hypersensitivity disorders. Animal model research supports a role of the microbiota in asthma and atopic disease development. Further, these model systems have identified an early life critical window, during which gut microbial dysbiosis is most influential in promoting hypersensitivity disorders. Until recently this critical window had not been characterized in humans, but now studies suggest that the ideal time to use microbes as preventative treatments or diagnostics for asthma in humans is within the first 100 days of life. This review outlines the major mouse-model and human studies leading to characterization of the early life critical window, emphasizing studies analyzing the intestinal and airway microbiotas in asthma and atopic disease. This research has promising future implications regarding childhood immune health, as ultimately it may be possible to therapeutically administer specific microbes in early life to prevent the development of asthma in children.Medicine, Faculty ofScience, Faculty ofOther UBCMicrobiology and Immunology, Department ofPediatrics, Department ofReviewedFacult

Analysis of Microbial Water Contamination, Soil Microbial Community Structure, and Soil Respiration in a Collaborative First-Year Students as Scholars Program (SAS)

The persistence of college students in STEM majors after their first-year of college is approximately 50%, with underrepresented populations displaying even higher rates of departure. For many undergraduates, their first-year in college is defined by large class sizes, poor access to research faculty, and minimal standing in communities of scholars. Pepperdine University and Whittier College, funded by a National Science Foundation award to Improve Undergraduate Stem Education (NSF IUSE), partnered in the development of first-year classes specifically geared to improve student persistence in STEM and academic success. This Students as Scholars Program (SAS) engaged first-year undergraduates in scholarly efforts during their first semester in college with a careful approach to original research design and mentoring by both faculty and upperclassmen experienced in research. Courses began by introducing hypothesis formulation and experimental design partnered with the scientific focus of each course (ecological, biochemical, microbiological). Students split into research teams, explored the primary literature, designed research projects, and executed experiments over a 6–7 week period, collecting, analyzing, and interpreting data. Microbiology-specific projects included partnerships with local park managers to assess water quality and microbial coliform contamination at specified locations in a coastal watershed. In addition, students explored the impact of soil salinity on microbial community structure. Analysis of these samples included next-generation sequencing and microbiome compositional analysis via collaboration with students from an upper division microbiology course. This cross-course collaboration facilitated additional student mentoring opportunities between upperclassmen and first-year students. This approach provided first-year students an introduction to the analysis of complex data sets using bioinformatics and statistically reliable gas-exchange replicates. Assessment of the impact of this program revealed students to view the research as challenging, but confidence building as they take their first steps as biology majors. In addition, the direct mentorship of first-year students by upperclassmen and faculty was viewed positively by students. Ongoing assessments have revealed SAS participants to display a 15% increased persistence rate in STEM fields when compared to non-SAS biology majors