Ozgur Celebi

Diarrhea-predominant irritable bowel syndrome (IBS-D) is a functional gastrointestinal disorder associated with gut microbiota dysbiosis, intestinal barrier dysfunction, and low-grade inflammation. This study aimed to evaluate the effects of Akkermansia muciniphila Muc T (ATCC BAA-835) on gut microbiota composition, intestinal barrier integrity, and TLR4/NF-κB/NLRP2-mediated inflammatory signaling in a stress-induced rat model of IBS-D. IBS-D was induced in rats using combined chronic and acute stress paradigms. Animals received A. muciniphila supplementation during the experimental period. Serum inflammatory cytokines and tight junction–related proteins were quantified by ELISA. Protein expression levels of TLR4, NF-κB, and NLRP2 were assessed by Western blotting. Gut microbiota composition was analyzed using 16 S rRNA gene sequencing of fecal samples. Histopathological and immunofluorescence analyses were performed to assess tissue inflammation and cellular damage. IBS-D rats exhibited increased inflammatory cytokine levels, impaired tight junction protein expression, activation of the TLR4/NF-κB/NLRP2 pathway, and significant alterations in gut microbiota diversity. A. muciniphila supplementation significantly attenuated inflammatory responses, restored intestinal barrier–associated proteins, and suppressed inflammatory signaling. Microbiota analysis revealed partial correction of dysbiosis, including increased abundance of beneficial taxa such as Faecalibacterium prausnitzii. A. muciniphila alleviates IBS-D–associated intestinal inflammation and barrier dysfunction by modulating gut microbiota composition and inflammatory signaling pathways, supporting its potential as a microbiota-based therapeutic strategy for IBS-D.

Antibiotic resistance is one of the most important problems threatening global public health by complicating the treatment of infections worldwide. The increase in resistant microorganisms creates a serious economic and social burden on healthcare systems and increasingly limits treatment options. Conscious use of antibiotics, infection control measures and the development of alternative treatment strategies are vital to ensure sustainability in health. Klebsiella pneumoniae is the most common gram-negative bacterium among urinary tract infections. Treatment of infections has become difficult due to the resistance to beta-lactam antibiotics. Bee venom (BV) and nanovesicle fractions isolated from BV are bioactive compounds with antimicrobial and antibiofilm activity. The aim of this study was to determine the antimicrobial and antibiofilm effects of BVand bee venom-derived nanovesicle fractions against the nosocomial infection agent K. pneumoniae, and to evaluate CTX-M PCR band detection under the tested conditions. Minimum inhibitory concentration (MIC), antibiofilm activity, fractional inhibition concentrations (FIC), CTX-M PCR band detection, and viability rates in L929 cells were evaluated for both BVand the bee venom-derived nanovesicle fraction against K. pneumoniae. MIC value of nanovesicle fractions isolated from BVwas determined as 1.95 mg/L. In combination with piperacillin and tazobactam, a synergistic effect was detected with a value of 0.5. Antibiofilm activity was measured with the highest absorbance value of 0.163 and 0.094 for BV nanovesicle fractions. A detectable CTX-M PCR band was observed in the BVgroup at 0.5× MIC, whereas no detectable band was observed at both concentrations by day 4. In the bee venom-derived nanovesicle fraction group, no detectable CTX-M PCR band was observed at 2× MIC and 0.5× MIC under the tested conditions. In contrast, detectable CTX-M PCR bands were observed in the piperacillin-tazobactam group. It was reported that the combination groups decreased the viability rate in L929 cell lines. The bee venom-derived nanovesicle fraction showed antimicrobial, antibiofilm, and PCR-based detection findings under the tested conditions, supporting the need for further investigation in broader in vitro and in vivo models.

Candida albicans is an opportunistic pathogen that can cause invasive infections, especially under conditions of immunosuppression and dysbiosis. Its presence alongside Pseudomonas aeruginosa and Escherichia coli may lead to polymicrobial biofilm-related infections. Due to rising antimicrobial resistance, alternative therapies are being explored, including luteolin, a natural flavonoid with reported in vitro antimicrobial activity. This study evaluated the in vitro antimicrobial and antibiofilm effects of luteolin against C. albicans, E. coli, and P. aeruginosa, both individually and in combination. Methods involved determining minimum inhibitory concentrations, using scanning electron microscopy, fibroblast viability tests, ELISA-based cytokine measurements, and RT-qPCR analysis of key biofilm- and quorum-sensing-related genes (luxS, lasI, and ALS1). MIC values were 0.011 mg/mL for individual strains and 0.046 mg/mL for the polymicrobial mixture. Luteolin treatment reduced microbial adherence and improved fibroblast viability compared to infected controls. Infection increased IL-1β levels and decreased IL-10 levels, effects that luteolin partially reversed. RT-qPCR showed downregulation of selected biofilm-related genes at 2×MIC. These findings demonstrate luteolin's measurable antimicrobial and anti-biofilm effects in vitro under controlled laboratory conditions, supporting further validation in preclinical models to assess translational potential.

Pancreatic cancer, characterized by its aggressive progression and limited therapeutic options, remains a malignancy with high mortality rates. This study evaluates the potential of bacterial extracellular vesicles (EVs) as immunotherapeutic carriers, focusing on Neisseria elongata-derived exosomes conjugated with a methanol extract of Cassia fistula, a plant with known anticancer properties. The cytotoxic and apoptotic effects of this complex were systematically analyzed using the PANC-1 pancreatic cancer cell line. MTT and LDH assays revealed a concentration-dependent reduction in cell viability and enhanced cytotoxicity. Mechanistic analyses demonstrated upregulation of pro-apoptotic BAX/BCL-2 ratio and modulation of PTEN/AKT signaling pathways, indicating activation of intrinsic apoptosis. Furthermore, increased levels of the pro-inflammatory cytokine IL-1β and suppression of anti-inflammatory IL-10 suggested immunomodulatory effects. Elevated reactive oxygen species (ROS) levels corroborated the induction of oxidative stress-mediated apoptosis. These results underscore the dual functionality of Neisseria elongata exosomes as both drug carriers and biological response modifiers. The biocompatibility and targeting efficiency of bacterial EVs position them as a novel therapeutic platform for gastrointestinal cancers. This study provides the first preclinical evidence supporting the use of non-pathogenic bacterial exosomes in oncology, highlighting their translational potential for improving treatment outcomes in pancreatic cancer.

Bacterial outer membrane vesicles (OMVs) are emerging as natural nanocarriers for cancer therapy due to their ability to deliver bioactive molecules and to penetrate the tumor microenvironment. This study investigated the combined effects of Escherichia coli-derived OMVs and Myristica fragrans extract on pancreatic ductal adenocarcinoma (PDAC) cells. OMVs (50 µg/mL) and M. fragrans extract (IC₅₀: 25 µg/mL) significantly reduced PANC-1 cell viability and increased LDH release after 24 h of treatment (p < 0.01). The combination treatment induced oxidative stress, evidenced by increased total oxidant status and decreased antioxidant capacity. Molecular analysis showed upregulation of PTEN expression, reduced phosphorylated AKT levels, and an increased IL-1β/IL-10 ratio. These changes elevated the Bax/Bcl-2 ratio and activated caspase-3, indicating induction of apoptosis (p < 0.01). Our findings suggest that OMVs can effectively deliver M. fragrans phytochemicals to cancer cells, modulating oxidative balance and triggering apoptosis through the PTEN/AKT signaling pathway. This study provides preclinical evidence that combinations of microbial vesicles and plant extracts may enhance therapeutic efficacy against PDAC.