Exploring the relationship between gut microbiota and breast cancer risk in European and East Asian populations using Mendelian randomization.

BACKGROUND: Several studies have explored the potential link between gut microbiota and breast cancer; nevertheless, the causal relationship between gut microbiota and breast cancer remains unclear. METHODS: We utilized summary statistics from genome-wide association studies (GWAS) of the gut microbiome from the MiBioGen project with summary data from GWAS on breast cancer from the FinnGen consortium and the IEU database, with the IEU data sourced from the Biobank Japan. Preliminary statistical analyses were conducted using inverse variance weighting (IVW), supplemented by various sensitivity analysis methods, including MR-Egger regression, weighted median, weighted mode, simple median, and simple mode, to ensure the robustness of our findings. Heterogeneity and pleiotropy were assessed to avoid misleading conclusions caused by unconsidered confounders or non-specific effects of genetic variants, ensuring that the results reflect a genuine causal relationship. RESULTS: In European populations, four types of gut microbiota were associated with breast cancer. The genus Erysipelatoclostridium was positively associated with the risk of breast cancer, with an odds ratio (OR) of 1.21 (95% confidence interval [CI] 1.083-1.358), false discovery rate (FDR) = 0.0039. The class Coriobacteriia, order Coriobacteriales, and family Coriobacteriaceae, which belong to the same phylogenetic system, showed a consistent inversely association with breast cancer risk, with an OR of 0.757 (95% CI 0.616-0.930), FDR = 0.0281. In East Asian populations, three types of gut microbiota were related to breast cancer. The Eubacterium ruminantium group was positively associated with breast cancer risk, with an OR of 1.259 (95% CI 1.056-1.499), FDR = 0.0497. The families Porphyromonadaceae and Ruminococcaceae were inversely associated with breast cancer risk, with ORs of 0.304 (95% CI 0.155-0.596), FDR = 0.0005, and 0.674 (95% CI 0.508-0.895), FDR = 0.03173, respectively. However, these two taxa had limited instrumental variables, restricting the statistical power and potentially affecting the interpretation of the results. CONCLUSION: This MR analysis demonstrated a probable causal link between specific gut microbiota and breast cancer. This study, through Mendelian randomization analysis comparing European and East Asian populations, reveals that gut microbiota may influence breast cancer risk differently across populations, providing potential directions for developing targeted prevention and treatment methods.

Nutrition Intervention and Microbiome Modulation in the Management of Breast Cancer.

Breast cancer (BC) is one of the most common cancers worldwide and a leading cause of cancer-related deaths among women. The escalating incidence of BC underscores the necessity of multi-level treatment. BC is a complex and heterogeneous disease involving many genetic, lifestyle, and environmental factors. Growing evidence suggests that nutrition intervention is an evolving effective prevention and treatment strategy for BC. In addition, the human microbiota, particularly the gut microbiota, is now widely recognized as a significant player contributing to health or disease status. It is also associated with the risk and development of BC. This review will focus on nutrition intervention in BC, including dietary patterns, bioactive compounds, and nutrients that affect BC prevention and therapeutic responses in both animal and human studies. Additionally, this paper examines the impacts of these nutrition interventions on modulating the composition and functionality of the gut microbiome, highlighting the microbiome-mediated mechanisms in BC. The combination treatment of nutrition factors and microbes is also discussed. Insights from this review paper emphasize the necessity of comprehensive BC management that focuses on the nutrition-microbiome axis.

Long-term intermittent caloric restriction remodels the gut microbiota in mice genetically prone to breast cancer.

OBJECTIVES: Gut microbiota dysbiosis is among the risk factors for breast cancer development, together with genetic background and dietary habits. However, caloric restriction has been shown to remodel the gut microbiota and slow tumor growth. Here, we investigated whether the gut microbiota mediates the preventive effects of long-term chronic or intermittent caloric restriction on breast cancer predisposition. METHODS: 10-week-old transgenic breast cancer-prone mice were randomly assigned to dietary groups (ad libitum, chronic caloric restriction, and intermittent caloric restriction groups) and fed up to week 81. Stool samples were collected at weeks 10 (baseline), 17 (young), 49 (adult), and 81 (old). 16S rRNA gene sequencing was performed to identify the gut microbiota profile of the different groups. In order to investigate the breast cancer gut microbiota profile within genetically predisposed individuals regardless of diet, mammary tumor-bearing mice and mammary tumor-free but genetically prone mice were selected from the ad libitum group (n = 6). RESULTS: Intermittent caloric restriction increased the microbial diversity of adult mice and modified age-related compositional changes. A total of 13 genera were differentially abundant over time. Pathogenic Mycoplasma was enriched in the re-feeding period of the old intermittent caloric restriction group compared with baseline. Furthermore, mammary tumor-free mice showed shared gut microbiota characteristics with mammary tumor-bearing mice, suggesting an early link between genetic predisposition, gut microbiota, and breast cancer development. CONCLUSIONS: Our study revealed the role of gut microbes in the preventive effects of caloric restriction against breast cancer development, implying the significance of diet and microbiome interplay.

Elucidating the Intricate Roles of Gut and Breast Microbiomes in Breast Cancer Metastasis to the Bone.

BACKGROUND: Breast cancer is the most predominant and heterogeneous cancer in women. Moreover, breast cancer has a high prevalence to metastasize to distant organs, such as the brain, lungs, and bones. Patients with breast cancer metastasis to the bones have poor overall and relapse-free survival. Moreover, treatment using chemotherapy and immunotherapy is ineffective in preventing or reducing cancer metastasis. RECENT FINDINGS: Microorganisms residing in the gut and breast, termed as the resident microbiome, have a significant influence on the formation and progression of breast cancer. Recent studies have identified some microorganisms that induce breast cancer metastasis to the bone. These organisms utilize multiple mechanisms, including induction of epithelial-mesenchymal transition, steroid hormone metabolism, immune modification, bone remodeling, and secretion of microbial products that alter tumor microenvironment, and enhance propensity of breast cancer cells to metastasize. However, their involvement makes these microorganisms suitable as novel therapeutic targets. Thus, studies are underway to prevent and reduce breast cancer metastasis to distant organs, including the bone, using chemotherapeutic or immunotherapeutic drugs, along with probiotics, antibiotics or fecal microbiota transplantation. CONCLUSIONS: The present review describes association of gut and breast microbiomes with bone metastases. We have elaborated on the mechanisms utilized by breast and gut microbiomes that induce breast cancer metastasis, especially to the bone. The review also highlights the current treatment options that may target both the microbiomes for preventing or reducing breast cancer metastases. Finally, we have specified the necessity of maintaining a diverse gut microbiome to prevent dysbiosis, which otherwise may induce breast carcinogenesis and metastasis especially to the bone. The review may facilitate more detailed investigations of the causal associations between these microbiomes and bone metastases. Moreover, the potential treatment options described in the review may promote discussions and research on the modes to improve survival of patients with breast cancer by targeting the gut and breast microbiomes.

A Clustering Study of Sociodemographic Data, Dietary Patterns, and Gut Microbiota in Healthy and Breast Cancer Women Participating in the MICROMA Study.

SCOPE: This work is part of the clinical study NCT03885648 registered in ClinicalTrials.gov, aimed at studying the relationship among breast cancer, microbiota, and exposure to environmental pollutants. As a first step, we characterized and evaluated risk factors of the participants. METHODS AND RESULTS: A case-control study was designed with breast cancer (cases, n = 122) and healthy women (controls, n = 56) recruited in two hospitals of Andalusia (Southern Spain). Participants answered questionnaires of Mediterranean diet adherence and food frequency. Data were collected from medical histories and microbiota was analyzed on stool samples. Most cases (78.2%) were diagnosed as stages I and II. Cases had higher age, body mass index (BMI), glucose, cholesterol, and potassium values than controls. Cases exhibited higher adherence to the Mediterranean diet and their food consumption was closer to that dietary pattern. A hierarchical cluster analysis revealed that the Bacillota/Bacteroidota ratio was the most relevant variable in women with breast cancer, which was higher in this group compared with controls. CONCLUSION: Although cases exhibited higher adherence to the Mediterranean diet compared with controls, they presented features and microbiota alterations typical of the metabolic syndrome, probably due to their higher BMI and reflecting changes in their lifestyle around the time of diagnosis.

Exploring the Relationship between MicroRNAs, Intratumoral Microbiota, and Breast Cancer Progression in Patients with and without Metastasis.

Breast cancer (BC) continues to pose a significant burden on global cancer-related morbidity and mortality, primarily driven by metastasis. However, the combined influence of microRNAs (miRNAs) and intratumoral microbiota on BC metastasis remains largely unexplored. In this study, we aimed to elucidate the interplay between intratumoral microbiota composition, miRNA expression profiles, and their collective influence on metastasis development in BC patients by employing 16S rRNA sequencing and qPCR methodologies. Our findings revealed an increase in the expression of miR-149-5p, miR-20b-5p, and miR-342-5p in metastatic breast cancer (Met-BC) patients. The Met-BC patients exhibited heightened microbial richness and diversity, primarily attributed to diverse pathogenic bacteria. Taxonomic analysis identified several pathogenic and pro-inflammatory species enriched in Met-BC, contrasting with non-metastatic breast cancer (NonMet-BC) patients, which displayed an enrichment in potential probiotic and anti-inflammatory species. Notably, we identified and verified a baseline prognostic signature for metastasis in BC patients, with its clinical relevance further validated by its impact on overall survival. In conclusion, the observed disparities in miRNA expression and species-level bacterial abundance suggest their involvement in BC progression. The development of a prognostic signature holds promise for metastasis risk assessment, paving the way for personalized interventions and improved clinical outcomes in BC patients.

Breast Cancer: Extracellular Matrix and Microbiome Interactions.

Breast cancer represents the most prevalent form of cancer and the leading cause of cancer-related mortality among females worldwide. It has been reported that several risk factors contribute to the appearance and progression of this disease. Despite the advancements in breast cancer treatment, a significant portion of patients with distant metastases still experiences no cure. The extracellular matrix represents a potential target for enhanced serum biomarkers in breast cancer. Furthermore, extracellular matrix degradation and epithelial-mesenchymal transition constitute the primary stages of local invasion during tumorigenesis. Additionally, the microbiome has a potential influence on diverse physiological processes. It is emerging that microbial dysbiosis is a significant element in the development and progression of various cancers, including breast cancer. Thus, a better understanding of extracellular matrix and microbiome interactions could provide novel alternatives to breast cancer treatment and management. In this review, we summarize the current evidence regarding the intricate relationship between breast cancer with the extracellular matrix and the microbiome. We discuss the arising associations and future perspectives in this field.

The immunoregulatory role of gut microbiota in the incidence, progression, and therapy of breast cancer.

Breast cancer (BrCa) is the most prevalent malignant tumor in women and one of the leading causes of female mortality. Its occurrence and progression are influenced by various factors, including genetics, environment, lifestyle, and hormones. In recent years, the gut microbiota has been identified as a significant factor affecting BrCa. The gut microbiota refers to the collective population of various microorganisms in the human gastrointestinal tract. Gut microbiota is closely associated with human health and disease development, participating in crucial physiological functions such as digestion, metabolism, immune response, and neural regulation. It has been found to influence the occurrence and treatment of BrCa through a variety of mechanisms. This article aims to review the immunomodulatory role of the gut microbiota in the development and treatment of BrCa.

The impact of intestinal and mammary microbiomes on breast cancer development: A review on the microbiota and oestrobolome roles in tumour microenvironments.

Microbiota affects carcinogenesis by altering energy equilibrium, increasing fat mass, synthesizing small signaling molecules, and formulating and regulating immune response and indigestible food ingredient, xenobiotic, and pharmaceutical compound metabolism. The intestinal microbiome can moderate oestrogen and other steroid hormone metabolisms, and secrete bioactive metabolites that are important for tumour microenvironment. Specifically, the breast tissue microbiome could become altered and lead to breast cancer development. The study of oestrobolome, the microbiomic component that metabolizes oestrogens, can contribute to better breast cancer understanding and subsequent treatment. Investigating oestrobolome-related oestrogen metabolism mechanisms in immune system regulation can shed light on how intestinal microorganisms regulate tumour microenvironment. Intestinal and regional breast microbiomes can determine treatment lines and serve as possible biomarkers for breast cancer. The aim of this study is to summarise current evidence on the role of microbiome in breast cancer progression with particular interest in therapeutic and diagnostic implementation.

Diet Modulates the Gut Microbiome, Metabolism, and Mammary Gland Inflammation to Influence Breast Cancer Risk.

Several studies indicate a strong link between obesity and the risk of breast cancer. Obesity decreases gut microbial biodiversity and modulates Bacteroidetes-to-Firmicutes phyla proportional abundance, suggesting that increased energy-harvesting capacity from indigestible dietary fibers and elevated lipopolysaccharide bioavailability may promote inflammation. To address the limited evidence linking diet-mediated changes in gut microbiota to breast cancer risk, we aimed to determine how diet affects the microbiome and breast cancer risk. For ten weeks, female 3-week-old BALB/c mice were fed six different diets (control, high-sugar, lard, coconut oil, lard + flaxseed oil, and lard + safflower oil). Fecal 16S sequencing was performed for each group. Diet shifted fecal microbiome populations and modulated mammary gland macrophage infiltration. Fecal-conditioned media shifted macrophage polarity and inflammation. In our DMBA-induced breast cancer model, diet differentially modulated tumor and mammary gland metabolism. We demonstrated how dietary patterns change metabolic outcomes and the gut microbiota, possibly contributing to breast tumor risk. Furthermore, we showed the influence of diet on metabolism, inflammation, and macrophage polarity. This study suggests that dietary-microbiome interactions are key mediators of breast cancer risk. Prevention Relevance: Our study demonstrates the impact of diet on breast cancer risk, focusing on the interplay between diet, the gut microbiome, and mammary gland inflammation.

Prevotella copri exhausts intrinsic indole-3-pyruvic acid in the host to promote breast cancer progression: inactivation of AMPK via UHRF1-mediated negative regulation.

Emerging evidence has revealed the novel role of gut microbiota in the development of cancer. The characteristics of function and composition in the gut microbiota of patients with breast cancer patients has been reported, however the detailed causation between gut microbiota and breast cancer remains uncertain. In the present study, 16S rRNA sequencing revealed that Prevotella, particularly the dominant species Prevotella copri, is significantly enriched and prevalent in gut microbiota of breast cancer patients. Prior-oral administration of P. copri could promote breast cancer growth in specific pathogen-free mice and germ-free mice, accompanied with sharp reduction of indole-3-pyruvic acid (IPyA). Mechanistically, the present of excessive P. copri consumed a large amount of tryptophan (Trp), thus hampering the physiological accumulation of IPyA in the host. Our results revealed that IPyA is an intrinsic anti-cancer reagent in the host at physiological level. Briefly, IPyA directly suppressed the transcription of UHRF1, following by the declined UHRF1 and PP2A C in nucleus, thus inhibiting the phosphorylation of AMPK, which is just opposite to the cancer promoting effect of P. copri. Therefore, the exhaustion of IPyA by excessive P. copri strengthens the UHRF1-mediated negative control to inactivated the energy-controlling AMPK signaling pathway to promote tumor growth, which was indicated by the alternation in pattern of protein expression and DNA methylation. Our findings, for the first time, highlighted P. copri as a risk factor for the progression of breast cancer.

Intratumoral Microbiota: Unraveling their Oncogenic Impact on Cancer Progression With Focus on Breast Cancer Therapeutic Outcomes.

The gut microbiota has been implicated in many cancers through the secretion of blood-traveling metabolites or activation of oncogenic signaling. Currently, specific microbial signatures have been detected in the human breast, which are different from other microbial-rich compartments, such as the intestine and skin. Changes in the breast microbiome profile have been shown to positively or negatively correlate with breast cancer development, progression, and therapeutic outcomes. However, studies regarding the role and underlying mechanism of intratumoral microbiota in breast cancer have remained concealed. This review aimed to provide an overview of the role of the intratumoral microbiome in tumorigenesis and tumor progression, and how these intratumoral microbiota affect breast cancer. We also discuss the potential of using the intratumoral microbiome as a biomarker or treatment alternative in breast cancers.

Multiomics-based molecular subtyping based on the commensal microbiome predicts molecular characteristics and the therapeutic response in breast cancer.

The gut microbiota has been demonstrated to be correlated with the clinical phenotypes of diseases, including cancers. However, there are few studies on clinical subtyping based on the gut microbiota, especially in breast cancer (BC) patients. Here, using machine learning methods, we analysed the gut microbiota of BC, colorectal cancer (CRC), and gastric cancer (GC) patients to identify their shared metabolic pathways and the importance of these pathways in cancer development. Based on the gut microbiota-related metabolic pathways, human gene expression profile and patient prognosis, we established a novel BC subtyping system and identified a subtype called "challenging BC". Tumours with this subtype have more genetic mutations and a more complex immune environment than those of other subtypes. A score index was proposed for in-depth analysis and showed a significant negative correlation with patient prognosis. Notably, activation of the TPK1-FOXP3-mediated Hedgehog signalling pathway and TPK1-ITGAE-mediated mTOR signalling pathway was linked to poor prognosis in "challenging BC" patients with high scores, as validated in a patient-derived xenograft (PDX) model. Furthermore, our subtyping system and score index are effective predictors of the response to current neoadjuvant therapy regimens, with the score index significantly negatively correlated with both treatment efficacy and the number of immune cells. Therefore, our findings provide valuable insights into predicting molecular characteristics and treatment responses in "challenging BC" patients.

A high-fat diet promotes cancer progression by inducing gut microbiota-mediated leucine production and PMN-MDSC differentiation.

A high-fat diet (HFD) is a high-risk factor for the malignant progression of cancers through the disruption of the intestinal microbiota. However, the role of the HFD-related gut microbiota in cancer development remains unclear. This study found that obesity and obesity-related gut microbiota were associated with poor prognosis and advanced clinicopathological status in female patients with breast cancer. To investigate the impact of HFD-associated gut microbiota on cancer progression, we established various models, including HFD feeding, fecal microbiota transplantation, antibiotic feeding, and bacterial gavage, in tumor-bearing mice. HFD-related microbiota promotes cancer progression by generating polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs). Mechanistically, the HFD microbiota released abundant leucine, which activated the mTORC1 signaling pathway in myeloid progenitors for PMN-MDSC differentiation. Clinically, the elevated leucine level in the peripheral blood induced by the HFD microbiota was correlated with abundant tumoral PMN-MDSC infiltration and poor clinical outcomes in female patients with breast cancer. These findings revealed that the "gut-bone marrow-tumor" axis is involved in HFD-mediated cancer progression and opens a broad avenue for anticancer therapeutic strategies by targeting the aberrant metabolism of the gut microbiota.

Marine seaweed endophytic fungi-derived active metabolites promote reactive oxygen species-induced cell cycle arrest and apoptosis in human breast cancer cells.

BACKGROUND: Endophytic fungi have an abundant sources rich source of rich bioactive molecules with pivotal pharmacological properties. Several studies have found that endophytic fungi-derived bioactive secondary metabolites have antiproliferative, anti-oxidant, and anti-inflammatory properties, but the molecular mechanism by which they induce cell cycle arrest and apoptosis pathways is unknown. This study aimed to determine the molecular mechanism underlying the anticancer property of the endophytic fungi derived active secondary metabolites on human breast cancer cells. METHODS: In this study, we identified four endophytic fungi from marine seaweeds and partially screened its phytochemical properties by Chromatography-Mass Spectrometry (GC-MS) analysis. Moreover, the molecular mechanism underlying the anticancer property of these active secondary metabolites (FA, FB, FC and FE) on human breast cancer cells were examined on MCF-7 cells by TT assay, Apoptotic assay by Acridine orang/Ethidium Bromide (Dual Staining), DNA Fragmentation by DAPI Staining, reactive oxygen species (ROS) determination by DCFH-DA assay, Cell cycle analysis was conducted Flow cytometry and the apoptotic signalling pathway was evaluated by westernblot analysis. Doxorubicin was used as a positive control drug for this experiment. RESULTS: The GC-MS analysis of ethyl acetate extract of endophytic fungi from the marine macro-algae revealed the different functional groups and bioactive secondary metabolites. From the library, we observed the FC (76%), FB (75%), FA (73%) and FE (71%) have high level of antioxidant activity which was assessed by DPPH scavenging assay. Further, we evaluated the cytotoxic potentials of these secondary metabolites on human breast cancer MCF-7 cells for 24 h and the IC50 value were calculated (FA:28.62 ± 0.3 µg/ml, FB:49.81 ± 2.5 µg/ml, FC:139.42 ± µg/ml and FE:22.47 ± 0.5 µg/ul) along with positive control Doxorubicin 15.64 ± 0.8 µg/ml respectively by MTT assay. The molecular mechanism by which the four active compound induced apoptosis via reactive oxygen species (ROS) and cell cycle arrest in MCF-7 cells was determined H2DCFDA staining, DAPI staining, Acridine orange and ethidium bromide (AO/EtBr) dual staining, flowcytometry analysis with PI staining and apoptotic key regulatory proteins expression levels measured by westernblot analysis. CONCLUSION: Our findings, revealed the anticancer potential of endophytic fungi from marine seaweed as a valuable source of bioactive compounds with anticancer properties and underscore the significance of exploring marine-derived endophytic fungi as a promising avenue for the development of novel anticancer agents. Further investigations are necessary to isolate and characterize specific bioactive compounds responsible for these effects and to validate their therapeutic potential in preclinical and clinical settings.

Microbiota enterotoxigenic Bacteroides fragilis-secreted BFT-1 promotes breast cancer cell stemness and chemoresistance through its functional receptor NOD1.

Tumor-resident microbiota in breast cancer promotes cancer initiation and malignant progression. However, targeting microbiota to improve the effects of breast cancer therapy has not been investigated in detail. Here, we evaluated the microbiota composition of breast tumors and found that enterotoxigenic Bacteroides fragilis (ETBF) was highly enriched in the tumors of patients who did not respond to taxane-based neoadjuvant chemotherapy. ETBF, albeit at low biomass, secreted the toxic protein BFT-1 to promote breast cancer cell stemness and chemoresistance. Mechanistic studies showed that BFT-1 directly bound to NOD1 and stabilized NOD1 protein. NOD1 was highly expressed on ALDH+ breast cancer stem cells (BCSCs) and cooperated with GAK to phosphorylate NUMB and promote its lysosomal degradation, thereby activating the NOTCH1-HEY1 signaling pathway to increase BCSCs. NOD1 inhibition and ETBF clearance increase the chemosensitivity of breast cancer by impairing BCSCs.

Association between oral microbiome and breast cancer in the east Asian population: A Mendelian randomization and case-control study.

BACKGROUND: The causal relationship between breast cancer (BC) and the oral microbiome remains unclear. In this case-control study, using two-sample Mendelian randomization (MR), we thoroughly explored the relationship between the oral microbiome and BC in the East Asian population. METHODS: Genetic summary data related to oral microbiota and BC were collected from genome-wide association studies involving participants of East Asian descent. MR estimates were generated by conducting various analyses. Sequencing data from a case-control study were used to verify the validity of these findings. RESULTS: MR analysis revealed that 30 tongue and 37 salivary bacterial species were significantly associated with BC. Interestingly, in both tongue and salivary microbiomes, we observed the causal effect of six genera, namely, Aggregatibacter, Streptococcus, Prevotella, Haemophilus, Lachnospiraceae, Oribacterium, and Solobacterium, on BC. Our case-control study findings suggest differences in specific bacteria between patients with BC and healthy controls. Moreover, sequencing data confirmed the MR analysis results, demonstrating that compared with the healthy control group, the BC group had a higher relative abundance of Pasteurellaceae and Streptococcaceae but a lower relative abundance of Bacteroidaceae. CONCLUSIONS: Our MR analysis suggests that the oral microbiome exerts a causative effect on BC risk, supported by the sequencing data of a case-control study. In the future, studies should be undertaken to comprehensively understand the complex interaction mechanisms between the oral microbiota and BC.

Microbiologic Profile of Nipple Swab Culture and its Association With Postoperative Complications in Prosthetic Breast Reconstruction.

BACKGROUND: In breast surgeries, a lactiferous duct leading to lactic glands of breast parenchyma allows direct contamination by normal bacterial flora of the nipple-areola complex. Complete blockage of nipple flora from the intraoperative field is almost impossible. OBJECTIVES: We aimed to analyze the microbiological profile of nipple flora of breast cancer patients who underwent an implant-based immediate breast reconstruction after a total mastectomy, and to evaluate the association of nipple bacterial flora with postoperative complications. METHODS: A retrospective chart review was performed of patients who underwent an implant-based immediate breast reconstruction after a total mastectomy. A nipple swab culture was performed preoperatively. Patient demographics, surgical characteristics, and complications were compared between positive and negative nipple swab culture groups. Microbiological profile data including antibacterial resistance were collected. RESULTS: Among 128 breasts, 60 cases (46.9%) had positive preoperative nipple swab culture results. Staphylococcus epidermidis accounted for 41.4% of microorganisms isolated. A multivariate logistic regression analysis of postoperative complications revealed that the presence of nipple bacterial flora was a risk factor for capsular contracture. Seven cases of postoperative infection were analyzed. In 2 cases (40% of pathogen-proven infection), the causative pathogen matched the patient's nipple bacterial flora, which was methicillin-resistant S. epidermidis in both cases. CONCLUSIONS: Nipple bacterial flora was associated with an increased risk of capsular contracture. Preoperative analysis of nipple bacterial flora can be an informative source for treating clinically diagnosed postoperative infections. More studies are needed to determine the effectiveness of active antibiotic decolonization of the nipple.

Correlation between Anxiety, Depression, and Intestinal Flora in Breast Cancer Patients: Based on 16S rRNA Sequence Analysis.

Objective: To explore intestinal flora differences in species diversity, community structure, and abundance of breast cancer and non-breast cancer populations with anxiety and depression and the corresponding group without anxiety and depression by 16S rRNA high-throughput sequencing technology. Method: Breast cancer and non-breast cancer participants were recruited based on the inclusion and exclusion criteria as the research subjects. The study employed the anxiety self-assessment scale and the depression self-rating scale in the questionnaire survey to collect data. Results: The scores of anxiety and depression of the four groups are as follows: In the breast cancer with anxiety and/or depression (BCAD) group, the anxiety score is 58.80 ± 5.27 and the depression score is 59.60 ± 4.94. In the breast cancer without anxiety and/or depression (BCWAD) group, the anxiety score is 36.53 ± 4.52 and the depression score is 38.20 ± 3.78. In the non-breast cancer group with anxiety and/or depression (HAD) group, the anxiety score is 57.87 ± 4.53 and the depression score is 59.13 ± 5.24. In the non-breast cancer group without anxiety and depression (HWAD) group, the anxiety score is 35.13 ± 5.28 and the depression score is 32.33 ± 4.37. Conclusion: The intestinal flora of the breast cancer patients is significantly different from those of non-breast cancer patients, suggesting that there is an internal relationship between the changes in the intestinal flora and the occurrence and development of breast cancer. People with anxiety and depression without breast cancer show changes in their intestinal flora, suggesting that the changes of the intestinal flora can indeed trigger anxiety and depression. For the breast cancer patients with anxiety and depression, the intestinal flora shows a decrease in diversity and abundance, suggesting that the intestinal flora of the breast cancer patients with anxiety and depression undergo further changes. Thus the intestinal flora can become a new tool for monitoring, preventing, and treating the breast cancer and negative emotions.

Depression promotes breast cancer progression by regulating amino acid neurotransmitter metabolism and gut microbial disturbance.

INTRODUCTION: Breast cancer (BC) is the most prevalent type of cancer and has the highest mortality among women worldwide. BC patients have a high risk of depression, which has been recognized as an independent factor in the progression of BC. However, the potential mechanism has not been clearly demonstrated. METHODS: To explore the correlation and mechanism between depression and BC progression, we induced depression and tumor in BC mouse models. Depression was induced via chronic unpredictable mild stress (CUMS) and chronic restraint stress (CRS). Amino acid (AA) neurotransmitter-targeted metabonomics and gut microbiota 16S rDNA gene sequencing were employed in the mouse model after evaluation with behavioral tests and pathological analysis. RESULTS: The tumors in cancer-depression (CD) mice grew faster than those in cancer (CA) mice, and lung metastasis was observed in CD mice. Metabonomics revealed that the neurotransmitters and plasma AAs in CD mice were dysregulated, namely the tyrosine and tryptophan pathways and monoamine neurotransmitters in the brain. Gut microbiota analysis displayed an increased ratio of Firmicutes/Bacteroides. In detail, the abundance of f_Lachnospiraceae and s_Lachnospiraceae increased, whereas the abundance of o_Bacteroidales and s_Bacteroides_caecimuris decreased. Moreover, the gut microbiota was more closely associated with AA neurotransmitters than with plasma AA. CONCLUSION: Depression promoted the progression of BC by modulating the abundance of s_Lachnospiraceae and s_Bacteroides_caecimuris, which affected the metabolism of monoamine neurotransmitters in the brain and AA in the blood.