Akkermansia muciniphila (A. muciniphila), a health-promoting bacterium in the human gut, is recognized for its role in improving immune function and metabolic health. Recent studies have uncovered its potential use as a therapeutic intervention for cancer treatment. This meta-analysis examines the impact of A. muciniphila, its extracellular vesicles (EVs), and Amuc protein on cancer outcomes in preclinical cancer models. Sixteen studies were included in the analysis through searches of relevant databases as of July 2025. Data on tumor number, volume, weight, and immune responses were extracted and analyzed. A. muciniphila and its derivatives significantly reduced tumor metrics across various cancers, including intestinal, colorectal, prostate, lung, gastric, hepatocellular, and ovarian. The intervention elevated interferon-gamma (IFNγ), CD8⁺ T cells, TNFα, and reduced IL-10 in the tumor microenvironment. Reduced spleen weight and systemic IL-6 levels indicated both local and systemic modulation of inflammation. Dose-specific effects included more substantial reductions in tumor number, size, and spleen weight at low doses (≤ 10⁸ CFU), as well as decreased tumor cell proliferation at high doses (≥ 10⁹ CFU). A. muciniphila and its derivatives exhibit significant potential in reducing cancer metrics. Their effects are mediated by regulating tumor growth, modulating both tumor microenvironment and systemic inflammatory pathways, enhancing immune regulation, and affecting gut microbiota composition. These results suggest that A. muciniphila may be a promising next-generation adjunct therapy for cancer, particularly in its non-live forms. Further exploration of the role of A. muciniphila's outer membrane proteins and metabolites through comprehensive clinical studies could unlock new therapeutic opportunities.
Background: Acute appendicitis is associated with characteristic changes in the intestinal microbiota, but direct sampling of appendiceal contents is invasive and cannot be performed in healthy controls. We therefore evaluated whether rectal swabs could partially capture appendiceal microbiome signatures in adults with acute appendicitis.
Methods: In a prospective cross-sectional study, we enrolled adults with acute appendicitis and healthy volunteers between October 2023 and December 2024. Four types of samples were collected: feces from healthy controls (HC), appendiceal luminal contents from patients with acute appendicitis (AC), intraoperative rectal swabs from patients with acute appendicitis (RS), and initial postoperative feces from patients with acute appendicitis (IF; first stool within 24 h after surgery). 16 S rRNA gene (V3-V4) sequencing was performed, and reads were processed with QIIME2. Alpha and beta diversity, differential taxonomic composition, and PICRUSt2-based functional predictions were compared across matrices. Genus-level and functional concordance between paired AC-RS samples was assessed.
Results: After quality control, 64 AC, 34 RS, 24 IF, and 29 HC samples were included. Phylogenetic diversity (PD whole-tree) was higher in AC and RS than HC, with AC also higher than RS; IF showed lower PD than AC. Bray-Curtis principal coordinate analysis showed AC forming a distinct cluster separated from HC and RS along PC1, whereas IF overlapped with HC and RS. AC, RS, and IF were enriched for Escherichia/Shigella and Fusobacterium and depleted in butyrate-producing genera such as Faecalibacterium compared with HC. In the 21 paired AC-RS cases, genus-level relative abundances and several predicted functional pathways showed concordance, indicating that RS captured many but not all appendiceal dysbiosis features.
Conclusions: Our findings suggest that intraoperative rectal swabs may partially reflect appendiceal microbiome alterations at the genus and pathway levels and may serve as a minimally invasive adjunct for microbiome profiling in acute appendicitis. However, these associations are inferred from 16 S amplicon data in a modestly sized, antibiotic-exposed cohort and should be validated using shotgun metagenomics in larger, clinically stratified populations.
Current improvements in microbiome research have illuminated the serious function of probiotics in modulating host gene expression through epigenetic mechanisms, particularly via the regulation of non-coding RNAs (ncRNAs) such as long non-coding RNAs (lncRNAs) and microRNAs (miRNAs). These regulatory RNAs are essential mediators of gene silencing, chromatin remodeling, and cellular signaling pathways implicated in immunity, inflammation, cancer, and neurodegenerative diseases. This review comprehensively examines current evidence on how specific probiotic strains influence miRNA and lncRNA expression, leading to beneficial outcomes in various pathological and physiological conditions. We explore the underlying molecular mechanisms by which probiotic-derived metabolites, like extracellular vesicles and short-chain fatty acids, interrelate with host transcriptional machinery and ncRNA biogenesis. Special emphasis is placed on disease models including inflammatory bowel disease, colorectal cancer, metabolic syndrome and Alzheimer's disease, highlighting the beneficial possible of targeting the gut microbiota-ncRNA axis. Moreover, we discuss the prospects for personalized microbiome-based interventions, challenges in clinical translation, and future directions for leveraging probiotic-ncRNA interactions in precision medicine. The integration of probiotics into epigenetic therapy represents a promising, non-invasive strategy for modulating gene expression and restoring homeostasis in complex diseases.
Background: Antibiotic resistance poses a major challenge in treating Vibrio cholerae infections. One promising method to counter resistance is the co-administration of antibiotics with non-antibiotic adjuvants to enhance their efficacy. This study investigated the combined action of sodium butyrate (SB) and tetracycline on tetracycline-resistant V. cholerae strains.
Results: The combined activity of SB and antibiotics was assessed on eight V. cholerae clinical isolates using the Fractional Inhibitory Concentration Index (FICI), with SB-Tetracycline showing strong synergy (FICI: 0.09-0.5). Functional and mechanistic studies, including time-kill kinetics, live/dead staining, SEM-based morphological analysis, and fluorometric assays, demonstrated a synergistic antibacterial effect of SB and Tetracycline. This effect was associated with increased membrane permeability, disruption of membrane integrity, dissipation of the proton motive force, and suppression of efflux activity. These changes collectively led to membrane damage, enhanced intracellular accumulation of Tetracycline, decreased intracellular ATP levels, and ultimately, bacterial cell death. Moreover, GM1-CT ELISA and fluorescence microscopy revealed the synergistic anti-virulence activity of the SB- Tetracycline combination. Finally, the combination of SB and Tetracycline showed enhanced efficacy in animal models compared with monotherapy.
Conclusion: The observed SB-Tetracycline synergy provides a promising therapeutic approach to overcome tetracycline resistance in V. cholerae, offering a potential adjunct strategy for the management of antibiotic-resistant cholera infections.
Ulcerative Colitis (UC) is a chronic illness that commonly demands the use of medication, sometimes for long term. In a DSS mouse model, we examined 5-aminosalicylic acid (5ASA) in comparison to a defined polyphenol-rich herbal mixture CSPG: Cirsium japonicum, Scutellaria baicalensis, Paeonia japonica, and Glycyrrhizae radix, using a two-phase approach. In phase 1 (days 1-14, without DSS stimulation), the herbal formula CSPG produced a more gut-friendly preventive profile compared to 5ASA in non-inflammatory condition:Unlike 5-ASA, which decreases microbial diversity as previously reported, CSPG preserved overall diversity and maintained protective taxa such as Ruminococcaceae uncultured ; and reduced inflammatory metabolites (uracil, glyceric acid, succinic acid) more effectively than 5ASA. Next, in phase 2 (days 15-24, with DSS inflammatory stimulation), CSPG matched first-line 5-ASA in suppressing inflammation (reduced colon shortening and procalcitonin). Its PI3K-Akt upregulation-together with NF-κB repression-was associated with more continuous ZO-1/ZO-2/occludin proteins expression and normalization of claudin-2 and MUC1/MUC2/MUC4, indicating barrier-repair capacity, a result supported by in vitro HT-29 experiments. Simultaneously, CSPG corrected DSS-induced dysbiosis more effectively than 5ASA: it increased SCFA-linked taxa (Prevotellaceae UCG-001 and Ruminococcus; 5ASA also rose but to a lesser extent), and reduced inflammation-associated groups ( [Eubacterium] siraeum group, and Erysipelotrichaceae). CSPG restored SCFAs and elevated glycine, proline, pyruvate, and myo-inositol, while reducing succinate and uracil-with stronger effects than 5-ASA for pyruvate, myo-inositol, and succinate, and comparable effects for butyrate. Although CSPG is not a single-target, rationally designed drug like 5ASA, it achieved comparable anti-inflammatory and barrier-repair effects and, unlike 5ASA, also improved gut microbiota composition and metabolite profiles, indicating potential advantages for long-term UC management.
Background: Brevilin A (Br) has shown potential in modulating inflammatory bowel disease (IBD). Our study aims to explore its mechanism of anti-inflammatory action.
Methods: Colitis was induced in C57BL/6 mice with dextran sulfate sodium (DSS), followed by treatment with or without Br(20 mg/kg). Fecal microbiota and metabolites were profiled by metagenomic sequencing and liquid chromatography-mass spectrometry (LC-MS), respectively. Furthermore, to delineate the essential role of the gut microbiota, we employed antibiotic-treated (microbiota-depleted) mice in our investigation of Br's mechanism of action.
Results: Br significantly alleviated DSS-induced colitis and modulated the gut microbiota profile. Specifically, Br enriched beneficial bacteria such as Lactobacillus, while suppressing pathogenic bacteria including Escherichia coli and Clostridium perfringens. Metabolomic analysis revealed that Br significantly altered bacterial metabolites, including 7-Oxolithocholic Acid, Kudinoside A, Veratrine, and Soyasaponin. These metabolites were linked to key pathways such as GPCR signaling, DNA damage response, aminoacyl-tRNA biosynthesis, riboflavin metabolism, and central carbon metabolism in cancer. Transcriptomic profiling indicated that Br inhibited the TNF-α signaling pathway, and this inhibition was confirmed as TNF-α overexpression reversed its anti-inflammatory effects. Furthermore, the therapeutic effects of Br were partially recapitulated in microbiota-depleted mice through fecal microbiota transplantation from Br-treated donors.
Conclusion: Br's ability to regulate gut microbiota and metabolites, improve gut barrier function, and eliminate inflammation by inhibiting TNF-α highlights its potential as a novel therapeutic medicine for IBD. Future research should focus on further exploring its mechanisms and clinical applications.
Background: Critical illness often leads to the development of intestinal dysbiosis, which can have a significant impact on disease outcome. Intestinal barrier dysfunction is a common problem in intensive care unit patients, particularly those with sepsis. Despite its importance, early and reliable diagnosis of barrier dysfunction and evaluation of therapeutic options remain lacking in clinical practice. Given that intestinal hyperpermeability is associated with increased translocation of luminal antigens and subsequent priming of naïve T cells, we hypothesized that analysis of circulating peripheral antigen-reactive T cells could provide insight into the functionality of the intestinal barrier.
Results: To test this hypothesis, 70 ICU patients were enrolled, including those with sepsis, those not meeting sepsis criteria, and COVID-19 patients, as well as 20 healthy volunteers. We identified a sepsis-specific T-helper cell signature in peripheral blood using the antigen-reactive T-cell enrichment (ARTE) technique followed by flow cytometric analysis. This signature was characterized by an expansion of gut trophic Bifidobacterium longum-reactive T-helper cells, indicating significant intestinal barrier dysfunction during sepsis.
Conclusion: This approach allows the study of intestinal barrier functionality and provides a means to monitor the effects of potential therapeutic interventions over time using blood samples.
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