Tiopronin

The H9N2 subtype of avian influenza virus remains a major threat to poultry production and public health, creating a need for effective vaccines that induce mucosal immunity. Oral immunization is attractive for poultry because it is convenient and suitable for mass application, but its efficacy is often limited by antigen degradation in the gastrointestinal tract and poor intestinal uptake. In this study, we developed a mannosylated chitosan-poly(lactic-co-glycolic acid) nanoemulsion loaded with Ganoderma lucidum triterpenes (MPG) as an oral mucosal adjuvant and delivery system, and subsequently incorporated inactivated H9N2 virus to prepare an oral inactivated vaccine. The MPG nanoemulsion showed a mean particle size of 439.7 ± 2.7 nm, with a negative zeta potential, good stability, protection under simulated gastric conditions, rapid release under intestinal conditions, favorable mucoadhesive properties and a promising immunostimulatory activity in vitro. Broiler chickens were orally immunized twice, and immune responses and protective efficacy were evaluated. Compared with the other groups, the MPG-adjuvanted vaccine significantly increased serum hemagglutination inhibition antibody titers and intestinal H9N2-specific secretory immunoglobulin A levels. After homologous challenge, vaccinated chickens showed reduced oropharyngeal viral shedding and milder lung lesions. In jejunal tissue, the MPG-adjuvanted vaccine increased the RNA expression of immunoglobulin A, polymeric immunoglobulin receptor, J-chain, IL-17, TNF-α, and IL-10, suggesting enhanced intestinal antibody transport and local immune responses. These results indicate that MPG improves the oral adjuvant activity of Ganoderma lucidum triterpenes and enhances both systemic and intestinal immune responses to an inactivated H9N2 vaccine. This strategy may provide a practical approach for oral mucosal vaccination against H9N2 in poultry.

Recent research highlights the pivotal role of gut microbiota and bile acids as modulators of metabolic homeostasis in type 2 diabetes (T2D). The concomitant use of probiotics and ursodeoxycholic acid (UDCA) may potentiate glycemic and lipid control via complementary mechanisms.

To evaluate the metabolic effects of probiotic supplementation and its combination with UDCA in metformin-treated T2D patients.

In this monocentric, prospective, randomized, double-blind, controlled trial, 90 patients with T2D on metformin therapy were randomized into three groups: metformin-only (MG), metformin plus probiotic (MPG), and metformin plus probiotic plus UDCA (MPUG). The intervention lasted 4 weeks. Primary outcomes included changes in fasting glucose, postprandial glucose and HbA1c. Secondary outcomes included lipid profile, C-reactive protein (CRP), and fecal levels of probiotics and UDCA. Two visits were conducted during the study - at the beginning and at the end. Visits involved patient interviews, clinical data collection, anthropometric measurements, blood biochemical analyses, and stool sample analysis for the presence of probiotic culture and UDCA concentrations.

After 4 weeks, the MPUG group showed a significant reduction in fasting glucose (−1.7 mmol/L; 95% CI: −2.2 to −1.2), postprandial glucose (−1.3 mmol/L; 95% CI: −1.8 to −0.7), and HbA1c (−0.49%; 95% CI: −0.66 to −0.31) compared to the MG group. Total cholesterol and LDL cholesterol were also significantly reduced, while HDL increased. The concentration of Lactobacillus rhamnosus GG was highest in the MPUG group. No serious adverse events were reported.

Co-administration of probiotics and UDCA for four weeks in metformin-treated T2D patients significantly improves short-term glycemic control and lipid profiles. These promising results warrant validation in larger, longer-term clinical trials.