As the incidence of Breast cancer continues to rise globally, understanding the molecular mechanisms by which probiotics can influence cancer cell behavior is crucial. Thisresearch explores the gene regulatory mechanism ofpotential anti-cancer properties of cell-free supernatants derived from Bifidobacterium bifidum and Lactobacillus acidophilus on Breast cancer cell lines, including MCF-7 and MDA-MB-231. We utilized a variety of experimental techniques, including MTT assays, BrdU, flow cytometry, evaluation of caspase activity and BAX/BCL-2 ratio, RT-PCR, Western blot analysis, and mimic miRNA transfection, to evaluate apoptosis induction and uncover the involved gene regulatory mechanisms throughout miRNAs. After exposing the cells with probiotic supernatants for 48 h at concentrations between 0.5 and 40 µg/mL, we observed a significant induction of apoptosis in both cell lines. Our investigation centered on four oncomiRs: miR-21-5p, miR-155-5p, miR-150-5p, and miR-223-3p, revealing notable changes in the levels of miR-155-5p and miR-21-5p. Further analysis indicated that the supernatants increased the expression of their target genes and proteins, PDCD4 and PTEN, which are essential for regulating apoptosis as tumor suppressor factors. we confirmed this gene regulatory properties by transfection of mimic miR-21-5p and miR-155-5p, the anticipated increase in PDCD4 and PTENwas less pronounced in transfected cells. This finding suggests that probiotics can effectively downregulate certain oncomiRs and enhance their target tumor suppressor genes and protein levels. the down-regulation of oncomiRs may display positive effects of probiotics, leading to inhibition of tumor growth and anti-proliferative outcomes. Our results emphasize the intricate relationships among probiotics, miRNAs, and tumor suppressor proteins, highlighting their potential significance in cancer treatment. This study calls for further exploration of these interactions to develop improved therapeutic strategies for Breast cancer through the modulation of cellular pathways by probiotics.
S. Soheili, S. Barez, Seyed davar Siadat et al.· Scientific Reports· 0 citations
The human microbiome is a complex, multikingdom ecosystem where bacteria and fungi cohabit and interact. Despite their ecological and clinical significance, cross-kingdom dynamics remain poorly characterized due to dominant single-kingdom research approaches. To understand the principles structuring multi-kingdom microbial communities, we applied the sparse inference method SpiecEasi to 45 publicly available samples from the gastrointestinal tract, skin, and oral cavity. Bacterial (16S rRNA) and fungal (ITS) sequencing data were processed using QIIME2, managed in phyloseq, and co-occurrence networks were inferred via SpiecEasi with Meinshausen– Bühlmann estimation. To validate robustness, we employed SparCC as a secondary inference method and performed 100 bootstrap iterations. Body site stratification controlled for environmental confounders. Our analysis revealed a microbial network of 5,023 taxa (5,020 bacterial, 3 fungal) connected by 30,478 significant associations. Crucially, we identified 737 robust bacterial–fungal interkingdom interactions (689 positive, 48 negative) confirmed by both inference methods. The network exhibited sparse connectivity (density = 0.0024) and modular structure (modularity = 0.45). Hub analysis identified 15 keystone taxa, including Bacteroides uniformis and Faecalibacterium prausnitzii. Interaction patterns were body-site-specific (P < 0.001), with the gastrointestinal tract showing the highest interkingdom connectivity (385 edges). This study provides systematic evidence that bacterial–fungal interactions are abundant and integral to human microbiome architecture. The discovery of 737 cross-kingdom associations challenges the prevailing single-kingdom paradigm and advocates for an integrated multikingdom perspective. These interactions, particularly those mediated by keystone hubs, represent novel targets for microbiome-based therapeutics and diagnostics. Importance This study challenges the prevailing single-kingdom paradigm in microbiome research by demonstrating that bacterial–fungal interactions are abundant and integral to human microbiome architecture. The discovery of 737 cross-kingdom associations across three body sites provides a foundational resource for understanding multikingdom microbial ecology. The identification of keystone bacterial hubs—particularly Bacteroides uniformis and Faecalibacterium prausnitzii—as central connectors in interkingdom networks opens new avenues for microbiome-based therapeutics and diagnostics. Our integrated analytical framework, combining SpiecEasi and SparCC with body site stratification, offers a robust methodological template for future cross-kingdom studies.
A. Babaei, Seyed davar Siadat· bioRxiv· 0 citations
