In-Silico Characterization of Estrogen Reactivating β-Glucuronidase Enzyme in GIT Associated Microbiota of Normal Human and Breast Cancer Patients

Muccee, Fatima; Ghazanfar, Shahina A.; Ajmal, Wajya; Al-Zahrani, Majid

doi:10.3390/genes13091545

Cited by 16 publications

(11 citation statements)

References 59 publications

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“…Using BCA from the breast microbiome of the 94 datasets, the clustering analysis showed three optimal enterotypes, characterized by higher level of Rothia, Escherichia-shigella, and Psyhcrobacter, respectively. Escherichia-shigella, a member of the Proteobacteria phylum, harbors the β-glucuronidase enzymes whose activities block the conjugation of estrogens, along with other compounds, and leaves them as biologically active hormones, consequently, the elevated levels of circulating estrogens and its metabolites, thus increasing the risk of BC [ 37 , 38 , 39 ]. This insight into the microbial community within the tumor and the adjacent BC tissues may provide fundamental information for future investigations.…”

Section: Discussionmentioning

confidence: 99%

Metagenomics Analysis of Breast Microbiome Highlights the Abundance of Rothia Genus in Tumor Tissues

Kartti

Bendani

Boumajdi

et al. 2023

JPM

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Breast cancer is one of the main global priorities in terms of public health. It remains the most frequent cancer in women and is the leading cause of their death. The human microbiome plays various roles in maintaining health by ensuring a dynamic balance with the host or in the appearance of various pathologies including breast cancer. In this study, we performed an analysis of bacterial signature differences between tumor and adjacent tissues of breast cancer patients in Morocco. Using 16S rRNA gene sequencing, we observed that adjacent tissue contained a much higher percentage of the Gammaproteobacteria class (35.7%) while tumor tissue was characterized by a higher percentage of Bacilli and Actinobacteria classes, with about 18.8% and 17.2% average abundance, respectively. Analysis of tumor subtype revealed enrichment of genus Sphingomonodas in TNBC while Sphingomonodas was predominant in HER2. The LEfSe and the genus level heatmap analysis revealed a higher abundance of the Rothia genus in tumor tissues. The identified microbial communities can therefore serve as potential biomarkers for prognosis and diagnosis, while also helping to develop new strategies for the treatment of breast cancer patients.

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Section: Discussionmentioning

confidence: 99%

Metagenomics Analysis of Breast Microbiome Highlights the Abundance of Rothia Genus in Tumor Tissues

Kartti

Bendani

Boumajdi

et al. 2023

JPM

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“…Potential protein structure errors were detected using the ProSA web server based on the Z-score, and a Z-score > 0 indicates that there may be an error or unstable part in the protein model. Ramachandran plots were generated using UCLA-DOE LAB-SAVES v6.0 (https://saves.mbi.ucla.edu/ (accessed on 16 February 2022) following previous studies [43][44][45][46].…”

Section: Prediction Of Physicochemical Properties and Secondary/terti...mentioning

confidence: 99%

PP19128R, a Multiepitope Vaccine Designed to Prevent Latent Tuberculosis Infection, Induced Immune Responses In Silico and In Vitro Assays

et al. 2023

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Background: Latent tuberculosis infection (LTBI) is the primary source of active tuberculosis (ATB), but a preventive vaccine against LTBI is lacking. Methods: In this study, dominant helper T lymphocyte (HTL), cytotoxic T lymphocyte (CTL), and B-cell epitopes were identified from nine antigens related to LTBI and regions of difference (RDs). These epitopes were used to construct a novel multiepitope vaccine (MEV) based on their antigenicity, immunogenicity, sensitization, and toxicity. The immunological characteristics of the MEV were analyzed with immunoinformatics technology and verified by enzyme-linked immunospot assay and Th1/Th2/Th17 cytokine assay in vitro. Results: A novel MEV, designated PP19128R, containing 19 HTL epitopes, 12 CTL epitopes, 8 B-cell epitopes, toll-like receptor (TLR) agonists, and helper peptides, was successfully constructed. Bioinformatics analysis showed that the antigenicity, immunogenicity, and solubility of PP19128R were 0.8067, 9.29811, and 0.900675, respectively. The global population coverage of PP19128R in HLA class I and II alleles reached 82.24% and 93.71%, respectively. The binding energies of the PP19128R-TLR2 and PP19128R-TLR4 complexes were −1324.77 kcal/mol and −1278 kcal/mol, respectively. In vitro experiments showed that the PP19128R vaccine significantly increased the number of interferon gamma-positive (IFN-γ+) T lymphocytes and the levels of cytokines, such as IFN-γ, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and IL-10. Furthermore, positive correlations were observed between PP19128R-specific cytokines in ATB patients and individuals with LTBI. Conclusions: The PP19128R vaccine is a promising MEV with excellent antigenicity and immunogenicity and no toxicity or sensitization that can induce robust immune responses in silico and in vitro. This study provides a vaccine candidate for the prevention of LTBI in the future.

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“…As mentioned in the previous section, the gut microbiome is an important player in estrogen metabolism. Since 80% of breast cancer cases are estrogen receptor-positive, the deconjugation of estrogens by the gut microbiome is of relevance [ 19 , 57 , 58 , 59 , 60 , 61 ]. Aside from being more abundant in the gut of breast cancer patients, Clostridiales reactivates estrogens and increases their serum levels [ 45 ].…”

Section: Gut Microbiome and Cancermentioning

confidence: 99%

The Gut Microbiome and Female Health

Siddiqui

Makhlouf

Alharbi

et al. 2022

Biology

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The possession of two X chromosomes may come with the risk of various illnesses, females are more likely to be affected by osteoarthritis, heart disease, and anxiety. Given the reported correlations between gut microbiome dysbiosis and various illnesses, the female gut microbiome is worthy of exploration. Herein, we discuss the composition of the female gut microbiota and its dysbiosis in pathologies affecting the female population. Using PubMed, we performed a literature search, using key terms, namely: “gut microbiome”, “estrogen”, “menopause”, “polycystic ovarian syndrome”, “pregnancy”, and “menstruation”. In polycystic ovarian syndrome (PCOS), the abundance of Bacteroides vulgatus, Firmicutes, Streptococcus, and the ratio of Escherichia/Shigella was found to be increased while that of Tenericutes ML615J-28, Tenericutes 124-7, Akkermansia, Ruminococcaceae, and Bacteroidetes S24-7 was reduced. In breast cancer, the abundance of Clostridiales was enhanced, while in cervical cancer, Prevotella, Porphyromonas, and Dialister were enhanced but Bacteroides, Alistipes, and members of Lachnospiracea, were decreased. In ovarian cancer, Prevotella abundance was increased. Interestingly, the administration of Lactobacillus acidophilus, Bifidobacterium bifidum, Lactobacillus reuteri, and Lactobacillus fermentum ameliorated PCOS symptoms while that of a mix of Bifidobacterium lactis W51, Bifidobacterium bifidum W23, Lactobacillus brevis W63, Bifidobacterium lactis W52, Lactobacillus salivarius W24, Lactobacillus acidophilus W37, Lactococcus lactis W19, Lactobacillus casei W56, and Lactococcus lactis W58 alleviated vascular malfunction and arterial stiffness in obese postmenopausal women, and finally, while further research is needed, Prevotella maybe protective against postmenopausal bone mass loss. As several studies report the therapeutic potential of probiotics and since the gut microbiota of certain female pathological states has been relatively characterized, we speculate that the administration of certain bacterial species as probiotics is warranted, as novel independent or adjunct therapies for various female pathologies.

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In-Silico Characterization of Estrogen Reactivating β-Glucuronidase Enzyme in GIT Associated Microbiota of Normal Human and Breast Cancer Patients

Cited by 16 publications

References 59 publications

Metagenomics Analysis of Breast Microbiome Highlights the Abundance of Rothia Genus in Tumor Tissues

Metagenomics Analysis of Breast Microbiome Highlights the Abundance of Rothia Genus in Tumor Tissues

PP19128R, a Multiepitope Vaccine Designed to Prevent Latent Tuberculosis Infection, Induced Immune Responses In Silico and In Vitro Assays

The Gut Microbiome and Female Health

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