The gut microbiota, a dynamic and metabolically active microbial ecosystem, plays a pivotal role in regulating host digestion, immune homeostasis, metabolism, and hormone signaling. Among its specialized functions, the estrobolome (a collection of bacterial genes involved in estrogen metabolism) has emerged as a key regulator of systemic estrogen levels. Through microbial β-glucuronidase activity, estrogens undergo deconjugation and reabsorption, influencing the pathogenesis of hormone-receptor-positive breast cancers. Disruption of the gut microbial balance, termed dysbiosis, can result from dietary changes, antibiotic use, environmental toxins, and psychosocial stress. Dysbiosis alters intestinal permeability, immune responses, and microbial metabolite profiles, contributing to chronic inflammation and endocrine disruption. Mechanistic links between gut microbiota and breast cancer include altered estrogen recirculation, immunomodulation, shifts in microbial metabolites (e.g., SCFAs, bile acids, tryptophan derivatives), and stress-mediated signaling through the microbiota–gut–brain axis. Accumulating preclinical and clinical evidence reveals distinct microbial signatures in breast cancer patients, supporting a causal or contributory role of gut dysbiosis in tumorigenesis. In parallel, biotics (including probiotics, prebiotics, synbiotics, and postbiotics) offer promising avenues for modulating the microbiota. Certain strains of Lactobacillus (L.) and Bifidobacterium (B.) exhibit anti-inflammatory and estrogen-modulating effects, while dietary fibers and microbial metabolites may enhance epithelial integrity and immunocompetence. This review critically examines the interplay between gut microbiota and breast cancer, elucidates the mechanistic pathways involved, and evaluates the current evidence on microbiota-targeted interventions. We also highlight research gaps, safety considerations, and the potential for integrating microbiome modulation into personalized oncologic care. This review uniquely integrates mechanistic pathways with those supported by preclinical and clinical evidence on biotics, highlighting microbiome-based precision strategies for breast cancer prevention and management.

The gut microbiota a dynamic and metabolically active microbial ecosystem plays a pivotal role in regulating host digestion, immune homeostasis, metabolism, and hormone signaling. Among its specialized functions, the estrobolome (a collection of bacterial genes involved in estrogen metabolism) has emerged as a key regulator of systemic estrogen levels. Through microbial β-glucuronidase activity, estrogens undergo deconjugation and reabsorption, influencing the pathogenesis of hormone-receptor-positive breast cancers. Disruption of the gut microbial balance, termed dysbiosis, can result from dietary changes, antibiotic use, environmental toxins, and psychosocial stress. Dysbiosis alters intestinal permeability, immune responses, and microbial metabolite profiles contributing to chronic inflammation and endocrine disruption. Mechanistic links between gut microbiota and breast cancer include altered estrogen recirculation, immunomodulation, shifts in microbial metabolites (e.g., SCFAs, bile acids, tryptophan derivatives), and stress-mediated signaling through the microbiota-gut-brain axis. Accumulating preclinical and clinical evidence reveals distinct microbial signatures in breast cancer patients, supporting a causal or contributory role of gut dysbiosis in tumorigenesis. In parallel, biotics (including probiotics, prebiotics, synbiotics, and postbiotics) offer promising avenues for microbiota modulation. Certain strains of Lactobacillus and Bifidobacterium exhibit anti-inflammatory and estrogen-modulating effects, while dietary fibers and microbial metabolites may enhance epithelial integrity and immunocompetence. This review critically examines the interplay between gut microbiota and breast cancer, elucidates mechanistic pathways, and evaluates current evidence on microbiota-targeted interventions. We also highlight research gaps, safety considerations, and the potential for integrating microbiome modulation into personalized oncologic care.

Summary: Back ground: Tissue differentiation and organogenesis are exclusively embryonic-phase activities, and these two activities are strictly under the control of the embryonic proteome, the developing embryo is a prime source of molecules for regenerative therapy. Many ex-vivo rudimentary organoid culture studies confirmed the inherent biological function of embryonic factors. Before using embryonic proteins for in vivo therapies, their safety should be confirmed first. Hence, we aimed for an in vivo study to inject rat embryonic proteome extract (EPE) through the intravenous route and investigate the impact on immunological, biochemical, and hematological parameters in the adult rats. Methods: In this study, we isolated rat embryonic proteins from the 14 ^th , 16th, and 19 ^th embryonic days by homogenization of embryos and isolated protein extracts through ultra-centrifugation. Six pairs of rats have been taken; six are allotted for control, and six are for the embryonic extract injection. The isolated embryonic protein extract was injected intravenously into the treatment group of rats and the normal saline into the control group. After the injections, blood samples are collected from both the treated and control groups to analyse immunological markers Il6, CRP, biochemical parameters creatinine, urea, sugar, proteins, albumin, globulin, and hematological parameters total leucocyte count, neutrophils, and lymphocyte percentage Result: After the EPE injection, biochemical parameters, immunological markers, and hematological parameters were analyzed in both control and treated groups. All the above mentioned parameters are within normal limits. Statistical analyses were done using the t-test for unequal variance (p< 0.05). We observed no significant difference between the control and treated groups, so in vivo injections of embryonic protein extract is safe for the use of in vivo regenerative therapies. Conclusion: Despite extensive in vitro studies confirmed the biological function of embryonic growth factors for organ differentiations and rudimentary organoids, but in vivo clinical applications are not yet started because of immunogenicity, heterogeneity, and tumorigeniety. In our study we injected EPE intravenously and showed that EPE is non-immunogenic, non-heterogeneic, and non-tumorigenic. This study concludes that EPE is safe for in vivo injection, so that further studies can be continued for intra-organ injections for organ regenerative therapy.

Seronegative rheumatoid arthritis (negRA) is difficult to diagnose due to the absence of rheumatoid factor and anticitrullinated peptide antibodies. This observational case–control study analysed urine samples from 35 negRA patients and 25 healthy controls using integrated liquid chromatography–quadrupole time-of-flight mass spectrometry and gas chromatography–mass spectrometry. Data were processed using mass spectrometry–data independent analysis and evaluated with multivariate approaches, including orthogonal partial least squares discriminant analysis and receiver operating characteristic curve analysis. We identified distinct urinary metabolic alterations in negRA, with four metabolites showing moderate-to-excellent diagnostic accuracy (area under the curve: 0.78–0.91). Pathway analysis using the Kyoto Encyclopedia of Genes and Genomes indicated the involvement of redox regulation and nucleotide/cofactor metabolism. These findings support the potential of urine metabolomics as a non-invasive tool for biomarker discovery in negRA and warrant validation in larger cohorts.