Search Results (174)

Oral diseases such as periodontitis and dental caries, as well as conditions related to oral health such as halitosis, are closely associated with dysbiosis of the oral microbiota and continue to pose significant public health challenges worldwide. With the increasing resistance to existing antibiotics and side effects of chemical disinfectants, probiotics have emerged as promising alternatives for oral healthcare. This study aimed to evaluate the oral health efficacy and probiotic properties of Limosilactobacillus fermentum (L. fermentum) MG4717 isolated from the human oral cavity. L. fermentum MG4717 showed notable antimicrobial activity against the key oral pathogens Streptococcus mutans (S. mutans), Aggregatibacter actinomycetemcomitans (A. actinomycetemcomitans), Porphyromonas gingivalis (P. gingivalis), and Fusobacterium nucleatum (F. nucleatum) and effectively inhibited biofilm formation. Additionally, L. fermentum MG4717 significantly downregulated methionine gamma-lyase (mgl) mRNA expression in P. gingivalis, which is implicated in halitosis and pathogenicity. L. fermentum MG4717 strongly adhered to the KB and HT-29 epithelial cells and exhibited good resilience under simulated gastrointestinal conditions. Whole-genome sequencing (WGS) and average nucleotide identity (ANI) analysis confirmed strain identity (98.73% average nucleotide identity with L. fermentum DSM20052) and the absence of transferable antibiotic resistance genes. Safety assessments revealed no cytotoxicity, hemolytic activity, or bile salt hydrolase activity. These findings suggest that L. fermentum MG4717 has the potential to be used as a safe and effective oral probiotic beneficial for oral health. Full article

Background: Gallbladder hypomotility is a key pathogenic factor in cholelithiasis. Non-invasive interventions to enhance gallbladder contractility remain limited. Ultrasound therapy has shown promise in various muscular disorders, but its effects on gallbladder function are unexplored. Methods: This study employed low-intensity pulsed ultrasound (LIPUS) at a 3 MHz frequency and 0.8 W/cm² intensity with a 20% duty cycle to irradiate the gallbladder region of fasting guinea pigs. Gallbladder contractile function was evaluated through multiple complementary approaches: in vivo assessment via two-dimensional/three-dimensional ultrasound imaging to monitor volumetric changes; quantitative functional evaluation using nuclear medicine scintigraphy (^99mTc-HIDA); and ex vivo experiments including isolated gallbladder muscle strip tension measurements, histopathological analysis, α-smooth muscle actin (α-SMA) immunohistochemistry, and intracellular calcium fluorescence imaging. Results: Ultrasound significantly enhanced gallbladder emptying, evidenced by the volume reduction and increased ejection fraction. Scintigraphy confirmed accelerated bile transport in treated animals. Ex vivo analyses demonstrated augmented contractile force, amplitude, and frequency in ultrasound-treated smooth muscle. Histological examination revealed smooth muscle hypertrophy, α-SMA upregulation, and elevated intracellular calcium levels. Extended ultrasound exposure produced sustained functional improvements without tissue damage. Conclusions: Ultrasound effectively enhances gallbladder contractile function through mechanisms involving smooth muscle structural modification and calcium signaling modulation. These findings establish the experimental foundation for ultrasound as a promising non-invasive therapeutic approach to improve gallbladder motility and potentially prevent gallstone formation. Full article

This study investigated the influence of β-cyclodextrin (βCD) on the micellization behavior of two bile salt surfactants, sodium deoxycholate (NaDC) and sodium cholate (NaC), in aqueous solutions. Tensiometry, conductometric, and spectrofluorimetric techniques were employed to determine critical micelle concentrations (CMCs) in the presence of varying concentrations of βCD, as well as in the presence of inorganic salts (NaCl and CsCl). The results showed that βCD forms inclusion complexes with both bile salts, leading to an increase in their CMCs, consistent with a competitive interaction between micelle formation and complexation. The inclusion constants, determined graphically, revealed stronger complexation for NaDC than NaC, attributed to differences in hydrophobic surface area. Salt addition decreased the CMC of both surfactants, with CsCl having a more pronounced effect. However, salt presence also modulated the inclusion complex formation, suggesting specific ion effects influence the availability and behavior of βCD. These findings contribute to the understanding of bile salt–cyclodextrin interactions and their modulation by electrolytes, with implications for drug delivery and supramolecular chemistry. Full article

Clostridium scindens is a commensal gut bacterium capable of forming the secondary bile acids as well as converting glucocorticoids to androgens. Historically, only two strains, C. scindens ATCC 35704 and C. scindens VPI 12708, have been characterized to any significant extent. The formation of secondary bile acids is important in the etiology of cancers of the GI tract and in the prevention of Clostridioides difficile infection. We determined the presence and absence of bile acid inducible (bai) and steroid-17,20-desmolase (des) genes among C. scindens strains and the features of the pangenome of 34 cultured strains of C. scindens and a set of 200 metagenome-assembled genomes (MAGs) to understand the variability among strains. The results indicate that the C. scindens cultivars have an open pangenome with 12,720 orthologous gene groups and a core genome with 1630 gene families, in addition to 7051 and 4039 gene families in the accessory and unique (i.e., strain-exclusive) genomes, respectively. The pangenome profile including the MAGs also proved to be open. Our analyses reveal that C. scindens strains are distributed into two clades, indicating the possible onset of C. scindens separation into two species, as suggested by gene content, phylogenomic, and average nucleotide identity (ANI) analyses. This study provides insight into the structure and function of the C. scindens pangenome, offering a genetic foundation of significance for many aspects of research on the intestinal microbiota and bile acid metabolism. Full article

Clostridioides difficile Infection (CDI) continues to be a major cause of antibiotic-associated diarrhea and pseudomembranous colitis, fueled in large measure by virulence factors TcdA and TcdB. These giant glucosyltransferase toxins interfere with host cytoskeletal integrity and inflammatory signaling by inhibiting Rho GTPase; however, the detailed structural dynamics, receptor selectivity, and subcellular trafficking mechanisms remain in part unspecified. This review integrates recent insights from cryo-electron microscopy (cryo-EM) and X-ray crystallography to describe the quaternary architecture of TcdA/B, emphasizing conformational changes key to pore formation and endosomal escape. We also examine the genomic heterogeneity of hypervirulent C. difficile strains (e.g., ribotype 027), correlating toxin gene polymorphisms (e.g., tcdC mutations) with increased toxin production and virulence. Mechanistic explanations of toxin-driven inflammasome activation and epithelial barrier dysfunction are situated within host immune evasion mechanisms, including microbiota-derived bile acid regulation of toxin stability. Subsequent innovative therapeutic strategies, encompassing the utilization of engineered neutralizing antibodies that specifically target the autoprocessing domain alongside structure-guided small-molecule inhibitors, are subjected to a rigorous evaluation. By integrating structural biology, systems-level omics, and clinical epidemiology, this review establishes a comprehensive framework for understanding C. difficile toxin pathogenesis and guiding next-generation precision antimicrobials. Full article

Vibrio parahaemolyticus, a halophilic Gram-negative bacterium commonly found in aquatic products, can colonize the human small intestine, causing gastroenteritis and potentially leukemia. As a major intestinal pathogen, it poses a significant threat to public health. This study aims to investigate the phenotypic heterogeneity of V. parahaemolyticus in the low-salinity and bile salt environments of the human intestinal tract and to elucidate its mechanisms of tolerance and pathogenicity using proteomics. The experimental results indicated that under the low salinity and bile salts conditions of the human intestinal environment, the growth, motility, and biofilm formation of the strains were significantly inhibited. Proteomics analysis revealed that, under these conditions, the energy metabolism, chemotaxis system, flagellar motor, and ribosome-related proteins of V. parahaemolyticus were significantly affected, thereby influencing its growth, motility, and biofilm formation. Furthermore, the activation of the secretion system, particularly the T2SS, enhanced the virulence of secreted factors on host cells. Additionally, the activation of the β-lactam resistance pathway increased resistance to the intestinal environment, thereby enhancing the pathogenicity of V. parahaemolyticus. Full article

In our previous studies on the liver proteome of Holstein cows, the acyl-CoA oxidase 2 (ACOX2) gene was identified as a promising candidate for milk traits, being involved in the processes of fatty acid metabolism and bile acid formation. Herein, we evaluated its genetic effects on milk production traits in 922 Chinese Holstein cows. By sequencing the entire coding region and 2000 bp of the 5′ and 3′ flanking sequences of the ACOX2 gene, we identified a total of five SNPs, including one SNP in the 5′ UTR, one in intron 5, and three in the 3′ flanking region. Using an animal model, we found that the SNPs rs109066086, rs109665171, and rs454339362 were significantly associated with at least one of the milk production traits, including 305-day milk yield, milk fat yield, milk protein yield, milk fat percentage, and milk protein percentage in the first lactation (p ≤ 4.03 × 10⁻²). And in the second lactation, all five SNPs were significantly associated with at least three of the milk production traits (p ≤ 1.17 × 10⁻²). We also found that in the second lactation, the SNP rs209677248 had a high phenotypic variance rate for milk protein percentage, with a value of 4.90%. With Haploview 4.2, it was observed that the four SNPs formed two haplotype blocks, which were significantly associated with the 305-day milk, fat, and protein yields (p ≤ 1.03 × 10⁻²; p ≤ 8.60 × 10⁻³; p ≤ 3.20 × 10⁻³). In addition, it was predicted that the T allele in the SNP rs109066086 created TFBSs for transcription factors NC2R2 and TFAP4, thereby potentially affecting ACOX2 expression. Overall, our results provide the first confirmation of the genetic effects of the ACOX2 gene on milk yield and composition traits in dairy cattle and revealed the referable molecular markers for genomic selection. Full article

Background and Clinical Significance: Progressive familial intrahepatic cholestasis (PFIC) refers to a heterogeneous group of autosomal recessive disorders consisting of mutations of hepatocyte transporting-system genes involved in bile formation. The exact prevalence remains unknown but is estimated at 1 in 500.000 for PFIC 3, caused by mutations in the ABCB4 gene. We report three cases of PFIC 3 from the patient’s sister, brother, and cousin, diagnosed in our Pediatric Department in 2022–2023. Case Presentation: Case 1: A 10-year-old girl was admitted for jaundice and abdominal pain. She was diagnosed with severely advanced hepatic cirrhosis and massive cholestasis. Genetic testing showed ABCB4 homozygous mutation. She rapidly developed fulminant liver failure, and a living donor liver transplant was performed. Case 2: A 6-year-old brother was previously diagnosed with cholestatic hepatitis of unknown cause back in 2018 and presented with similar features (generalized jaundice, severe pruritus with generalized scratching lesions); symptoms had progressively developed from the first year of life. He also exhibited particular facial features (big forehead, twisted ear lobe, straight nose). He received cadaveric liver transplantation. Case 3: Nephew of first two children, a 3-year-5-month-old boy, was admitted for failure to thrive and a one-year history of jaundice, pruritus, and splenomegaly. He was tested positive for homozygous ABCB4 mutation. He is currently under medical treatment with stable liver function. Conclusions: The clinical significance of this particular homozygous variant identified in ABCB4 in our series of cases (c.2534G>T (p.Gly845Val)) was uncertain up to this case report. The present data provide convincing evidence as to the correlation between this mutation and the clinical phenotype of PFIC 3. Full article

A biofilm is a community of microbial cells which are enclosed in an external matrix and separated by a network of water channels attached to natural or artificial surfaces. Biofilms formed inside biliary stents consist of a mixed spectrum of bacterial communities, most of which usually originate from the intestines. The patency of biliary stents is the most important problem. Stent occlusion can threaten the health and even life of patients. The main cause of this phenomenon is bile sludge, which is an excellent environment for the multiplication and existence of microorganisms. Due to the great clinical importance of maintaining the patency of biliary stents, several methods have been developed to prevent the accumulation of sludge and the subsequent formation of biofilm; these include, among others, the use of anti-adhesive materials, coating the inner surface of stents with metal cations (silver, copper) or other antimicrobial substances, the implementation of biodegradable drug-eluting biliary stents and the development of a new stent design with an anti-reflux effect. This article presents the latest information on the formation of biofilms in biliary stents, as well as historical and future methods of prevention. Full article

The discovery and design of antiviral agents have gained unprecedented significance due to the emergence of global health threats. The use of synthetic chemistry has enabled the modification of existing molecules and the creation of entirely novel compounds. In our laboratory, we have enzymatically synthesized a novel bioconjugate, lithocholic acid oleate (LO), derived from lithocholic acid (LCA), a bile acid that has been proven by researchers to exhibit antiviral activity in vitro. The study presented herein describes the preparative synthesis, formulation, and evaluation of LO both in vitro and in vivo for its antiviral activity against human herpes simplex virus 1 (HSV-1) as a model of viral infection. Evaluation of cytotoxicity using A549 cells indicated that a combination of LO (400 μM) and LCA (30 μM) exhibited a favorable safety profile while effectively inhibiting HSV-1 infection comparable to acyclovir treatment. Furthermore, in the in vivo assay, animals treated with an oily formulation containing 7% LO; 0.50% LCA; and 3% oleic acid (OA), 48 h prior to virus exposure, showed results even superior to a 5% acyclovir commercial formulation in terms of scar formation and wound recovery. These promising results enable the development of new preventive products against HSV-1 and probably other viruses. Full article

Various prenatal and postnatal factors such as gestational age, mode of delivery, sex, antibiotic exposure, feeding type, duration of feed and other exposures associated with the hospital environment can drive the formation of gut microbiota. In the current study, we examined the role of all these factors in the gut microbiota of healthy Indian preterm infants admitted to NICU in the first four weeks of life. Preterm neonates admitted to the NICU from April 2023 and October 2023 were recruited and fecal samples were collected weekly once beginning from the seventh day till the 30th day of life. 16s rRNA gene sequencing was performed on the NovaSeq 6000 platform. The PICRUSt2 tool was used to predict the functional profiles of the gut microbiome. A total of 61 samples were collected from 16 preterm infants. Alpha and beta diversity showed the administration of probiotics, postnatal age, mode of delivery, and sex of infants as major contributors to altered microbial diversity in preterm infants. The MaAsLin2 analysis showed that the supplementation of probiotics increased Bifidobacterium levels. PICRUSt2 analysis revealed that probiotic supplementation increased the bacterial genes responsible for bile acid metabolism and glycosphingolipid synthesis. Probiotics and postnatal age are responsible for alterations of the gut microbial composition in healthy preterm infants. Full article

Gallstone disease (GSD) is a common gastrointestinal disorder affecting approximately 10–20% of the global adult population, characterized by the presence of gallstones, predominantly cholesterol-based, in the gallbladder and/or biliary ducts. While many patients remain asymptomatic, more than 20% develop clinical symptoms such as abdominal pain, nausea, vomiting, jaundice, and anorexia, potentially leading to severe complications like acute cholecystitis and biliary pancreatitis. GSD has a significant genetic predisposition, with the variable prevalence of the disease according to ethnicity being highest in American and European countries and lowest in Asian and African populations. Numerous genes encoding membrane transporters involved in bile metabolism are associated with GSD, including in particular members of ATP-binding cassette transporters and others, which affect bile lithogenicity and contribute to the development of gallstones. Specific mutations in these genes are linked to an increased risk of gallstone formation, especially in individuals with certain hereditary conditions such as hemolytic diseases, thyroid disorders, and hyperparathyroidism. Advances in genetic studies have identified new variants that influence the risk of cholelithiasis, although the exact mechanisms remain partially understood in many cases. This review briefly summarizes the genetic causes of cholelithiasis, highlighting various pathogenetic mechanisms. It presents the currently used treatments and the potential implications of widely applied genetic diagnostics. Full article

Objectives: In hepatopancreatic diseases, stenting is widely employed to manage cholangitis and obstructive jaundice. Stent materials are primarily categorized as plastic or metal. Plastic stents have notable advantages, such as reduced likelihood of peripheral bile duct obstruction, a lower cost, and the ease of replacement compared to metallic stents. However, their patency period is shorter due to narrower diameters. Plastic stents are typically composed of materials like polyurethane or polyethylene. To improve patency, new dual-layer stents combine polyurethane with polytetrafluoroethylene (PTFE). PTFE, used in the inner layer, is expected to prevent biofilm formation. This study aimed to assess the clinical efficacy of this dual-layer stent. Methods: A retrospective analysis was performed on 48 cases (Group R) using REGULUS^® from November 2022 to November 2023 and 30 cases (Group IS) using inside-type plastic stents from January 2020 to November 2023 for malignant hilar and intrahepatic bile duct obstructions. Stent patency and clinical outcomes were compared between the groups. Results: There was no significant difference in the recurrent biliary obstruction (RBO) rate between the groups (p = 0.644). The time to recurrent biliary obstruction (TRBO) was 74 days in Group R and 118 days in Group IS, with no significant difference (p = 0.219). Conclusions: The dual-layer stent placed across the papilla demonstrated comparable clinical outcomes to inside-type stents. The PTFE inner layer likely reduces biofilm formation, enhancing patency. Across-the-papilla placement may facilitate reinterventions in challenging cases, broadening stent options. Full article

Lactobacillus, a genus of lactic acid bacteria, is known to coexist symbiotically in the female vaginal microbiota and has gained attention as a potential probiotic with benefits for female reproductive health. This study aimed to evaluate the probiotic potential of Lactobacillus gasseri BELG74(BELG74), isolated from the vaginal microbiota of Korean women, in promoting vaginal health through growth ability, pH reduction, lactic acid production, and antimicrobial activity. Among 36 Lactobacillus gasseri strains, BELG74 demonstrated the highest growth capacity at 1.84 × 10⁹ CFU/mL and the lowest pH of 3.84. BELG74 produced the most lactic acid at a concentration of 20.12 g/L, which correlated with anti-pathogenic activity against Gardnerella vaginalis, Fannyhessea vaginae, and Candida albicans of more than 90%. It also showed high acid resistance (92.2%) and bile resistance (25.3%), ensuring its survival through the gastrointestinal tract. Furthermore, BELG74 exhibited strong biofilm formation and adhesion capacity of 28.7% to HeLa cells, making it effective in colonizing the vaginal environment and suppressing pathogenic bacteria. The reduction of IL-1β by 63% suggested anti-inflammatory effects. Additionally, BELG74 effectively neutralized trimethylamine and ammonia by over 99.9%, suggesting its ability to reduce unpleasant vaginal odors. These findings indicate that BELG74 could be a promising probiotic for improving vaginal health, with further clinical studies needed to confirm these benefits. Full article

Background: Cholesterol gallstone disease (CGS) is often accompanied by gallbladder contraction dysfunction and chronic inflammation, but effective therapeutic options remain limited. This study investigates whether a low-intensity pulsed ultrasound (LIPUS) treatment can improve gallbladder motility and alleviate chronic inflammation while exploring the underlying mechanisms. Methods: Gallbladder motility was assessed through in vitro and in vivo contraction tests, while bile condition was evaluated by observing bile crystal clearance. Tissue analysis and Western blotting were performed to examine the expression of the cholecystokinin A receptor (CCKAR) and α-smooth muscle actin (α-SMA) as markers of gallbladder smooth muscle health and the inflammatory microenvironment. Blood cholesterol levels were measured via biochemical assays. Results: LIPUS treatment obviously enhanced gallbladder contractility in response to CCK-8 stimulation and accelerated bile crystal clearance. It also reduced inflammatory cell infiltration and tissue edema, and promoted new capillary formation in the gallbladder, mitigating the progression of CGS. Furthermore, LIPUS restored CCKAR expression and improved the thickness of the gallbladder smooth muscle layer, providing a structural basis for increased smooth muscle contractility. Conclusion: LIPUS improves gallbladder motility and reduces chronic inflammation in CGS by enhancing CCKAR expression and smooth muscle integrity. These findings highlight the potential of LIPUS as a non-invasive therapeutic approach for managing CGS. Full article