Search Results (635)

Background/Objectives: Bladder cancer is a common malignancy with a high rate of recurrence and progression. Recent studies have identified that the urinary microbiome can be a key factor in tumor pathogenesis, progression, and outcomes. This narrative review is designed to summarize current evidence regarding the urobiome and explore its diagnostic and therapeutic potential. Methods: Studies between 2019 and 2024 were identified through the PubMed/MEDLINE and Google Scholar databases. Case reports and non-English-language articles were excluded. Results: The main findings revealed that specific bacteria, viruses, and taxa are linked to bladder cancer presence, progression, and response to immunotherapy treatment. Urinary microbiota differ by tumor type, sex, smoking status, and occupational exposure to toxins. Conclusions: Urinary microbiome and certain types of viruses present in urine may serve as promising tools to enhance bladder cancer diagnosis and predict treatment response. However, larger longitudinal studies are needed to confirm and establish these findings. Furthermore, integration of the urinary microbiome in clinical practice and public health strategies may reduce disease-related burden. Full article

Fecal microbiota transplantation (FMT) promotes growth performance and intestinal development in yellow-feathered broilers, but whether the virome and metabolites contribute to its growth-promoting effect remains unclear. This study removed the microbiota from FMT filtrate using a 0.45 μm filter membrane, retaining the virome and metabolites to perform fecal virome transplantation (FVT), aiming to investigate its regulatory role in broiler growth. Healthy yellow-feathered broilers with high body weights (top 10% of the population) were used as FVT donors. Ninety-six 8-day-old healthy male yellow-feathered broilers (95.67 ± 3.31 g) served as FVT recipients. Recipient chickens were randomly assigned to a control group and an FVT group. The control group was gavaged with 0.5 mL of normal saline daily, while the FVT group was gavaged with 0.5 mL of FVT solution daily. Growth performance, immune and antioxidant capacity, intestinal development and related gene expression, and microbial diversity were measured. The results showed that FVT improved the feed utilization rate of broilers (the feed conversion ratio decreased by 3%; p < 0.05), significantly increased jejunal length (21%), villus height (69%), and crypt depth (84%) (p < 0.05), and regulated the jejunal barrier: insulin-like growth factor-1 (IGF-1) (2.5 times) and Mucin 2 (MUC2) (63 times) were significantly upregulated (p < 0.05). FVT increased the abundance of beneficial bacteria Lactobacillales. However, negative effects were also observed: Immunoglobulin A (IgA), Immunoglobulin G (IgG), Immunoglobulin M (IgM), Interleukin-1 beta (IL-1β), Interleukin-6 (IL-6), Tumor Necrosis Factor-alpha (TNF-α), and Interferon-gamma (IFN-γ) in broilers were significantly upregulated (p < 0.05), indicating immune system overactivation. Duodenal barrier-related genes Mucin 2 (MUC2), Occludin (OCLN), Claudin (CLDN1), and metabolism-related genes solute carrier family 5 member 1 (SLC5A1) and solute carrier family 7 member 9 (SLC7A9) were significantly downregulated (p < 0.05). The results of this trial demonstrate that, besides the microbiota, the gut virome and metabolites are also functional components contributing to the growth-promoting effect of FMT. The differential responses in the duodenum and jejunum reveal spatial heterogeneity and dual effects of FVT on the intestine. The negative effects limit the application of FMT/FVT. Identifying the primary functional components of FMT/FVT to develop safe and targeted microbial preparations is one potential solution. Full article

Codonopsis pilosula polysaccharides have demonstrated multiple biological activities including immune regulation, antitumor, and antioxidant properties. The rapid development and integrated application of multi-omics can facilitate the unraveling of the complex network of immune system regulation. In this study, C. pilosula alkali-extracted polysaccharide (CPAP) were prepared, and their effects on gut microbiota compositions, metabolic pathways, and protein expressions in peripheral blood and solid tumors in mice were further evaluated. The 16S rDNA sequencing results showed that CPAP could effectively promote the enrichment of intestinal Lactobacillus in tumor-bearing mice. In addition, it could be inferred from peripheral blood and solid tumor proteomics results that CPAP might activate T cell-mediated antitumor immune functions by regulating purine metabolism and alleviate tumor-caused inflammation by promoting neutrophil degranulation, finally inducing apoptosis in tumor cells by increasing oxidative stress. These results will provide a theoretical foundation and data support for the further development of CPAP as dietary adjuvants targeting immune deficiency-related diseases. Full article

Background/Objectives: Ulcerative colitis (UC) is characterized by the interplay between immune responses and dysbiosis in disease development. Aiming to provide additional insights into disease development and potential treatment strategies, the present study investigates the local effect of oral treatment with polysaccharides obtained from Auricularia auricula’s submerged culture in an experimental model of DSS-induced colitis and its impact on lesion resolution. Methods: The structure and monosaccharide composition of Auricularia polysaccharides were characterized through Nuclear Magnetic Resonance (NMR). To evaluate the effect of this polysaccharide on the murine model, wild-type and Dectin-1 knockout mice were treated or not with the exopolysaccharide (EPS) while under DSS consumption. During the experimental period, feces samples were collected to evaluate microbial shifts during disease development, and, finally, the colonic tissue was analyzed to assess the inflammatory process and cytokine production. Results: The EPS composition showed a polymeric mixture of glucans and fucogalactomannans. The treatment of the wild-type DSS-induced colitis group improved the inflammatory response by increasing gut–homeostatic cytokines, such as interleukin-10 (IL-10) and tumor necrosis factor-alpha (TNF-α). The Dectin-1 KO mice group did not show the same enhancement after EPS treatment. The microbiome analysis revealed a difference in the genotype, and the treatment modified the DSS microbiome modulation, with nine and four ASVs in WT and Dectin-1 KO mice, respectively. Conclusions: The EPS treatment demonstrated therapeutic potential in treating inflammatory intestinal diseases by modulating cytokine secretion and microbiota composition, which is dependent on the Dectin-1 receptor’s carbohydrate recognition. Full article

Background/Objectives: This study aimed to evaluate the effects of lung injury induced by insoluble uranium oxide particles on gut microbiota and related metabolites in rats. Methods: The rats were randomly divided into six UO₂ dose groups. A rat lung injury model was established through UO₂ aerosol. The levels of uranium in lung tissues were detected by ICP-MS. The expression levels of the inflammatory factors and fibrosis indexes were measured by enzyme-linked immunosorbent assay. Paraffin embedding-based hematoxylin & eosin staining for the lung tissue was performed to observe the histopathological imaging features. Metagenomic sequencing technology and HM700-targeted metabolomics were conducted in lung tissues. Results: Uranium levels in the lung tissues increased with dose increase. The expression levels of Tumor Necrosis Factor-α (TNF-α), Interleukin-1β (IL-1β), Collagen I, and Hydroxyproline (Hyp) in rat lung homogenate increased with dose increase. Inflammatory cell infiltration and the deposition of extracellular matrix were observed in rat lung tissue post-exposure. Compared to the control group, the ratio of Firmicutes and Bacteroides in the gut microbiota decreased, the relative abundance of Akkermansia_mucinphila decreased, and the relative abundance of Bacteroides increased. The important differential metabolites mainly include αlpha-linolenic acid, gamma-linolenic acid, 2-Hydroxybutyric acid, Beta-Alanine, Maleic acid, Hyocholic acid, L-Lysine, L-Methionine, L-Leucine, which were mainly concentrated in unsaturated fatty acid biosynthesis, propionic acid metabolism, aminoacyl-tRNA biosynthesis, phenylalanine metabolism, and other pathways in the UO₂ group compared to the control group. Conclusions: These findings suggest that uranium-induced lung injury can cause the disturbance of gut microbiota and its metabolites in rats, and these changes are mainly caused by Akkermansia_mucinphila and Bacteroides, focusing on unsaturated fatty acid biosynthesis and the propionic acid metabolism pathway. Full article

Objectives: Colorectal cancer (CRC) is a leading cause of cancer-related mortality, driven by chronic inflammation, gut microbiota dysbiosis, and complex tumor microenvironment interactions. Current therapies are limited by systemic toxicity and poor tumor accumulation. This study aimed to develop a ROS/enzyme dual-responsive oral drug delivery system, KGM-CUR/PSM microspheres, to achieve precise drug release in CRC and enhance tumor-specific drug accumulation, which leverages high ROS levels in CRC and the β-mannanase overexpression in colorectal tissues. Methods: In this study, we synthesized a ROS-responsive prodrug polymer (PSM) by conjugating polyethylene glycol monomethyl ether (mPEG) and mesalazine (MSL) via a thioether bond. CUR was then encapsulated into PSM using thin-film hydration to form tumor microenvironment-responsive micelles (CUR/PSM). Subsequently, konjac glucomannan (KGM) was employed to fabricate KGM-CUR/PSM microspheres, enabling targeted delivery for colorectal cancer therapy. The ROS/enzyme dual-response properties were confirmed through in vitro drug release studies. Cytotoxicity, cellular uptake, and cell migration were assessed in SW480 cells. In vivo efficacy was evaluated in AOM/DSS-induced CRC mice, monitoring tumor growth, inflammatory markers (TNF-α, IL-1β, IL-6, MPO), and gut microbiota composition. Results: In vitro drug release studies demonstrated that KGM-CUR/PSM microspheres exhibited ROS/enzyme-responsive release profiles. CUR/PSM micelles demonstrated significant anti-CRC efficacy in cytotoxicity assays, cellular uptake studies, and cell migration assays. In AOM/DSS-induced CRC mice, KGM-CUR/PSM microspheres significantly improved survival and inhibited CRC tumor growth, and effectively reduced the expression of inflammatory cytokines (TNF-α, IL-1β, IL-6) and myeloperoxidase (MPO). Histopathological and microbiological analyses revealed near-normal colon architecture and microbial diversity in the KGM-CUR/PSM group, confirming the system’s ability to disrupt the “inflammation-microbiota-tumor” axis. Conclusions: The KGM-CUR/PSM microspheres demonstrated a synergistic enhancement of anti-tumor efficacy by inducing apoptosis, alleviating inflammation, and modulating the intestinal microbiota, which offers a promising stimuli-responsive drug delivery system for future clinical treatment of CRC. Full article

REG3A, a prominent member of the human regenerating islet-derived (REG) lectin family, plays a pivotal and multifaceted role in immune defense, inflammation, and cancer biology. Primarily expressed in gastrointestinal epithelial cells, REG3A reinforces barrier integrity, orchestrates mucosal immune responses, and regulates host–microbiota interactions. It also functions as a potent non-enzymatic antioxidant, protecting tissues from oxidative stress. REG3A expression is tightly regulated by inflammatory stimuli and is robustly induced during immune activation, where it limits microbial invasion, dampens tissue injury, and promotes epithelial repair. Beyond its antimicrobial and immunomodulatory properties, REG3A contributes to the resolution of inflammation and the maintenance of tissue homeostasis. However, its role in cancer is highly context-dependent. In some tumor types, REG3A fosters malignant progression by enhancing cell survival, proliferation, and invasiveness. In others, it acts as a tumor suppressor, inhibiting growth and metastatic potential. These opposing effects are likely dictated by a combination of factors, including the tissue of origin, the composition and dynamics of the tumor microenvironment, and the stage of disease progression. Additionally, the secreted nature of REG3A implies both local and systemic effects, further modulated by organ-specific physiology. Experimental variability may also reflect differences in methodologies, analytical tools, and model systems used. This review synthesizes current knowledge on the pleiotropic functions of REG3A, emphasizing its roles in epithelial defense, immune regulation, redox homeostasis, and oncogenesis. A deeper understanding of REG3A’s pleiotropic effects could open up new therapeutic avenues in both inflammatory disorders and cancer. Full article

The beneficial effect of consuming fruits and vegetables in the prevention of chronic non-communicable diseases and healthy aging is well known. This is attributed to food and vegetable antioxidant and fiber content. The aim of this publication is to communicate the results of recent research on pectin in humans, to propose an increased consumption of fruits and vegetables, or their possible use as a food supplement. A comprehensive narrative review was conducted considering recent publications on pectin. The description of starch, pectin, the physicochemical changes caused by pectin, and the effect of pectin on the activity of amylase are reported. Dietary fiber and gut microbiota in human health are also described, with the production of saturated fatty acids with fewer than six carbon atoms. Finally, health effects such as anti-hyperglycemic and anti-hyperlipidemic activities, preventing and controlling obesity and heart disease, are analyzed, as well as other health effects in tumors, the gastrointestinal tract, and immunity. Considering the beneficial effects of pectin in health and the low consumption throughout the world, it is recommended to promote the consumption of fruits and vegetables to increase pectin intake in the human diet. Full article

As tumor research has deepened, the deregulation of cellular metabolism has emerged as yet another recognized hallmark of cancer. Tumor cells adapt different biochemical pathways to support their rapid growth, proliferation, and invasion, resulting in distinct anabolic and catabolic activities compared with healthy tissues. Certain metabolic shifts, such as altered glucose and glutamine utilization and increased de novo fatty acid synthesis, are critical early on, while others may become essential only during metastasis. These metabolic adaptations are closely shaped by, and in turn remodel, the tumor microenvironment, creating favorable conditions for their spread. Anticancer metabolic strategies should integrate pharmacological approaches aimed at inhibiting specific biochemical pathways with well-defined dietary interventions as adjunctive therapies, considering also the role of gut microbiota in modulating diet and treatment responses. Given the established link between the consumption of foods rich in saturated fatty acids and sugars and an increased cancer risk, the effects of diet cannot be ignored. However, current evidence from controlled and multicenter clinical trials remains insufficient to provide definitive clinical recommendations. Further research using modern omics methods, such as metabolomics, proteomics, and lipidomics, is necessary to understand the changes in the metabolic profiles of various cancers at different stages of their development and to determine the potential for modifying these profiles through pharmacological agents and dietary modifications. Therefore, clinical trials should combine standard treatments with novel approaches targeting metabolic reprogramming, such as inhibition of specific enzymes and transporters or binding proteins, alongside the implementation of dietary restrictions that limit nutrient availability for tumor growth. However, to optimize therapeutic efficacy, a precision medicine approach should be adopted that balances the destruction of cancer cells with the protection of healthy ones. This approach, among others, should be based on cell type-specific metabolic profiling, which is crucial for personalizing oncology treatment. Full article

Colorectal cancer (CRC) is a multifactorial disease increasingly recognized for its complex interplay with the gut microbiota. The disruption of microbial homeostasis—dysbiosis—has profound implications for intestinal barrier integrity and host immune function. Pathogenic bacterial species such as Fusobacterium nucleatum, Escherichia coli harboring polyketide synthase (pks) island, and enterotoxigenic Bacteroides fragilis are implicated in CRC through mechanisms involving mucosal inflammation, epithelial barrier disruption, and immune evasion. These pathogens promote pro-tumorigenic inflammation, enhance DNA damage, and suppress effective anti-tumor immunity. Conversely, commensal and probiotic bacteria, notably Lactobacillus and Bifidobacterium species, exert protective effects by preserving epithelial barrier function and priming host immune responses. These beneficial microbes can promote the maturation of dendritic cells, stimulate CD8⁺ T cell cytotoxicity, and modulate regulatory T cell populations, thereby enhancing anti-tumor immunity. The dichotomous role of the microbiota underscores its potential as both a biomarker and a therapeutic target in CRC. Recent advances in studies have explored microbiota-modulating strategies—ranging from dietary interventions and prebiotics to fecal microbiota transplantation (FMT) and microbial consortia—as adjuncts to conventional therapies. Moreover, the composition of the gut microbiome has been shown to influence the responses to immunotherapy and chemotherapy, raising the possibility of microbiome-informed precision oncology therapy. This review synthesizes the current findings on the pathogenic and protective roles of bacteria in CRC and evaluates the translational potential of microbiome-based interventions in shaping future therapeutic paradigms. Full article

Deciphering the spatiotemporal distribution of bacteria during breast cancer progression may provide critical insights for developing bacterial-based therapeutic strategies. Using a murine breast cancer model, we longitudinally profiled the microbiota in breast tumor tissue, mammary gland, spleen, and cecal contents at 3-, 5-, and 7- weeks post-tumor implantation through 16S rRNA gene sequencing. Breast tumor progression was associated with lung metastasis and splenomegaly, accompanied by distinct tissue-specific microbial dynamics. While alpha diversity remained stable in tumors, mammary tissue, and cecal contents, it significantly increased in the spleen (p < 0.05). Longitudinal analysis revealed a progressive rise in Firmicutes and a decline in Proteobacteria abundance within tumors, mammary tissue, and cecum, whereas the spleen microbiota displayed unique phylum-level compositional shifts. Tissue- and time-dependent microbial signatures were identified at phylum, genus, and species levels during breast tumor progression. Strikingly, the spleen microbiota integrated nearly all genera enriched in other sites, suggesting its potential role as a microbial reservoir. Gut-associated genera (Lactobacillus, Desulfovibrio, Helicobacter) colonized both cecal contents and the spleen, with Lactobacillus consistently detected across all tissues, suggesting microbial translocation. The spleen exhibited uniquely elevated diversity and compositional shifts, potentially driving splenomegaly. These results delineated the trajectory of microbiota translocation and colonization, and demonstrated tissue-specific microbial redistribution during breast tumorigenesis, offering valuable implications for advancing microbiome-targeted cancer therapies. Full article

Colorectal cancer (CRC) is one of the most prevalent and lethal oncological diseases worldwide, with a concerning rise in incidence, particularly in developing countries. Recent advances in genetic sequencing have revealed that the gut microbiome plays a crucial role in CRC development. Mechanisms such as chronic inflammation, metabolic alterations, and oncogenic pathways have demonstrated that dysbiosis, a disruption of the gut microbiome, is linked to CRC. Associations have been found between tumor progression, treatment resistance, and pathogenic microbes such as Fusobacterium nucleatum and Escherichia coli. A promising approach for CRC prevention and treatment is microbiome manipulation through interventions such as probiotics, prebiotics, fecal microbiota transplantation, and selective antibiotics. This article explores how gut microbiome alterations influence CRC pathogenesis and examines microbiome modulation strategies currently used as adjuncts to traditional treatments. Advances in artificial intelligence, single-cell and spatial transcriptomics, and large-scale initiatives such as the ONCOBIOME Project are paving the way for the identification of microbiome-derived biomarkers for early CRC detection and personalized treatment. Despite promising progress, challenges such as interindividual variability, causal inference, and regulatory hurdles must be addressed. Future integration of microbiome analysis into multi-omics frameworks holds great potential to revolutionize precision oncology in CRC management. Full article

Background/Objectives: Breast cancer (BC) is the leading cause of cancer incidence and mortality among women and the recent identification of a resident mammary microbiota has highlighted its potential role in breast carcinogenesis. Given that environmental and socioeconomic factors influence both BC prevalence and tumor-associated bacterial composition, this study aimed to evaluate the compositional and functional features of the mammary microbiota in cancerous (oncobiome) and adjacent healthy BC tissues from patients living in urban and rural areas. Methods: Microbiota composition in both the oncobiome and adjacent healthy BC tissues was analyzed using 16S rRNA sequencing. Results: Significant variations in breast oncobiome composition were observed among BC patients from urban and rural areas. A statistically significant β dispersion among breast oncobiome of patients from urban or rural areas was highlighted. Specifically, the genera Selenomonas, Centipeda, Leptotrichia, Neisseria and Porphyromonas were found exclusively in BC tissues of patients from rural areas. Additionally, bacteria from the Neisseriaceae, Porphyromonadaceae, and Selenomonadaceae families, as well as the Selenomonas genus, were significantly enriched in the oncobiome of rural BC patients. Furthermore, the results of the PICRUSt2 (phylogenetic investigation of communities by reconstruction of unobserved states) revealed a significant increase in phospholipid biosynthesis pathways in breast oncobiome of patients from rural areas compared to those from urban areas. Conclusions: This study provides evidence of distinct compositional and functional differences in the breast oncobiome between BC patients from rural and urban areas. These findings suggest that environmental factors influence local microbiome composition, potentially contributing to BC development and/or progression. Full article

Periodontitis is an inflammatory disease that affects the periodontal supporting tissues. Its cardinal clinical manifestations encompass gingival inflammation, periodontal pocket formation, and alveolar bone resorption. Urolithin A (UA), a gut microbiota-derived metabolite of ellagitannins, is known for its anti-inflammatory and osseous-protective properties. Nonetheless, the impact of UA on periodontitis remains unknown. To investigate the preventive effect of UA, we employed a lipopolysaccharide (LPS)-induced inflammation model in RAW 264.7 mouse macrophages, a receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation model, and a ligature-induced periodontitis model in mice. The expression of inflammatory factors (tumor necrosis factor-α, TNF-α; interleukin-6, IL-6) was analyzed to assess anti-inflammatory efficacy. Bone loss in mice with periodontitis was assessed through histological and imaging techniques, including haematoxylin and eosin staining to evaluate alveolar bone morphology, Masson’s trichrome staining to visualize collagen fiber distribution, and micro-computed tomography scanning to quantify bone structural parameters. Additionally, we investigated the underlying mechanisms by examining osteoclast activity through tartrate-resistant acid phosphatase staining and the expression levels of proteins RANKL and osteoprotegerin (OPG). We found that UA reduced IL-6 and TNF-α levels in vitro and in vivo, inhibited osteoclast differentiation, and decreased the RANKL/OPG ratio in periodontitis mice. Full article

Background: Symbiotic gut microbiota can enhance cancer therapy efficacy, while treatment-induced dysbiosis may reduce effectiveness or increase toxicity. Our preclinical study compared the anticancer effects and impact on fecal microbiota and metabolites of two water-soluble SN-38 derivatives (BN-MePPR and BN-MOA), with those observed after treatment with Irinotecan, and the FOLFOX regimen in NOD scid gamma mice bearing patient-derived colon adenocarcinoma xenografts (CRC PDX). Methods: Five individual experiments with Irinotecan and its derivatives and eight individual experiments with FOLFOX were conducted using eight CRC PDX models. Chemotherapeutics were administered intraperitoneally 4–5 times at 5-day intervals. Fecal samples were collected before and after treatment. Microbiota composition was analyzed by 16S rRNA gene (V3–V4 regions) sequencing. Mass spectrometry was used to quantify short-chain fatty acids (SCFAs) and amino acids (AAs). Results: All treatments significantly inhibited tumor growth versus controls. However, no significant changes were observed in gut microbiota α- and β-diversity between treated and untreated groups. Tumor progression in controls was associated with increased abundance of Marvinbryantia, Lactobacillus, Ruminococcus, and [Eubacterium] nodatum group. FOLFOX-treated mice showed increased Marvinbryantia, Bacteroides, and Candidatus Arthromitus, and decreased Akkermansia. No distinct taxa changes were found in the Irinotecan or derivative groups. SCFA levels remained unchanged across groups, while BN-MePPR, BN-MOA, and Irinotecan all increased AA concentrations. Conclusions: Contrary to earlier toxicological data, these findings indicate a relatively limited impact of the tested chemotherapeutics on the gut microbiome and metabolome, emphasizing the importance of research method selection in preclinical studies. Full article