Ucar, Mahmut; Celebi, Demet; Celebi, Ozgur; Baser, Sumeyye; Guler, Mustafa Can; Tanyeli, Ayhan; Kılıclıoglu, Metin; Yıldırım, Serkan

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.

Erbaş, Elif; Üstündağ, Hilal; Gedikli, Semin; Gelen, Volkan; Parlak, Seçil Nazife; Çelebi, Demet; Kara, Adem

Polystyrene nanoplastics (PsNPs) represent an emerging environmental threat with potential adverse effects on pancreatic tissue. This study investigated whether probiotic supplementation (PB) could attenuate PsNPs-induced pancreatic injury by modulating oxidative stress, inflammation, and P2X7R/Caspase-1 signaling. Forty male Sprague–Dawley rats were divided into five groups: control, probiotic (PB 1010), PsNPs (100 nm, 10 mg/kg/day), PsNPs + PB 109, and PsNPs + PB 1010. After 35 days of oral administration, oxidative stress markers, inflammatory cytokines, P2X7R/Caspase-1 gene expression, signaling proteins (NF-κB, PI3K, p-PI3K, p38 MAPK, TGF-β), histopathology, and immunohistochemistry (Bcl-2, Caspase-3, Insulin, P2X7 and Caspase-1) were evaluated. PsNPs significantly upregulated P2X7R and Caspase-1 expression (Sp < 0.0001), elevated NF-κB levels (p < 0.0001), increased IL-1β and TNF-α, and induced oxidative stress with elevated MDA, depleted SOD (p < 0.001), and reduced GSH (p < 0.01). Histopathology revealed inflammatory infiltration and cellular degeneration. Insulin immunoreactivity decreased while Caspase-3 increased. Probiotic co-treatment at 101⁰ CFU/day significantly attenuated P2X7R/Caspase-1 upregulation, reduced NF-κB expression, restored SOD activity and GSH levels, normalized cytokines, and preserved Insulin immunoreactivity. PsNPs induce pancreatic injury through P2X7R/Caspase-1/NF-κB signaling activation. Multi-strain probiotic supplementation exerts dose-dependent protective effects by modulating purinergic signaling and restoring antioxidant capacity.