Nosocomial infections in patients with severe acute pancreatitis (SAP) are frequently driven by impaired intestinal barrier function, which facilitates bacterial translocation and contributes to adverse clinical outcomes. Saccharomyces boulardii (S. boulardii) can reconstitute gut microbiota composition. We investigated whether S. boulardii combined with enteral nutrition (EN) affects the microbiome and nosocomial infections in SAP.

This study is a single centre, open-label randomized controlled trial. We included 50 patients with SAP in a Chinese gastroenterology intensive care unit (ICU), randomized to Probiotic group (S. boulardii and EN) or the Control group (EN). Throat/oropharyngeal and rectal swabs were collected from patients with SAP on days 0, 1, 3, 6, 9, 12, and 15 of ICU admission. The primary endpoints were nosocomial infection and fungemia, whereas the secondary endpoints were ICU mortality, 28-day mortality, ICU stay, and length of hospital stay. All samples were subjected to full-length 16 s rRNA and internal transcribed spacer (ITS) sequencing. Multivariate analysis was performed using normalized microbial and corresponding clinical data.

After data processing, 213 16S rRNA and 120 ITS samples were analysed. S. boulardii prevented nosocomial infections (0/27 in the Probiotic group vs 5/23 in the Control group; P < 0.05). Intestinal fungi were closely associated with nosocomial infections. Bioinformatic analysis showed that S. boulardii prevented nosocomial infections by reducing intestinal bacterial perturbation and inhibiting the proliferation of Enterococcus in the intestine, and Candida in the respiratory tract and intestines.

S. boulardii in patients with SAP may positively alter the respiratory and intestinal microbiome and decrease the incidence of nosocomial infections.

This study was approved by the Ethics Committee of Xinqiao Hospital, Army Medical University, Chongqing China (2021-yd030–01), which was retrospectively registered at the Chinese Clinical Trial Registry (ChiCTR2200056011, Date of Registration: 30/01/2022 https://www.chictr.org.cn/showproj.html?proj=151215).

To investigate the efficacy of zingerone（Zin）on dextran sodium sulfate（DSS）-induced colitis in mice and its potential immunomodulatory mechanism.

SPF C57BL/6 male mice aged 6 to 8 weeks were divided into control group（Water）, model group（DSS）, and Zin intervention group（DSS+Zin）, with 5 mice in each group. Acute ulcerative colitis model was constructed using DSS solution, and the changes in body weight, disease activity index（DAI）, colon length, and histopathological scores were compared among the groups. RT-qPCR and corresponding reagents and kits were employed to detect the mRNA and protein expression of inflammatory cytokines in the colonic tissue, respectively. The effects of Zin on T cell subsets and on the expression of transcription factor RORγt were determined by flow cytometry in vitro and in vivo. Moreover, the transcriptional activity of RORγt and activity of Rorc promoter were examined using dual-luciferase reporter system.

As compared with the control group, the mice in the DSS group showed shorter colon length, higher scores of DAI and histopathological index（P<0.05）, with increased mRNA levels of IL-17A, IL-21, IL-22, IL-6, IL-1 β and IFN-γ（P<0.05）, while decreased mRNA level of TGF-β（P<0.05）. The protein levels of IL-17A, IL-17F, IL-22, and IFN-γ were also upregulated in the DSS group（P<0.05）. However, Zin treatment significantly relieved the above clinical symptoms and reversed the expression of above inflammatory factors（P<0.05）. Flow cytometry indicated that Zin inhibited the differentiation of Th17 cells and the expression of RORγt, and promoted the differentiation of Treg cells both in vitro and in vivo（P<0.05）, but the differentiation of Th1 subset was not affected. The dual-luciferase reporter assay demonstrated that the transcriptional activity of RORγt and Rorc promoter activity were remarkably suppressed after Zin treatment（P<0.05）.

Zin alleviates DSS-induced colitis in mice by regulating the balance of Th17/Treg cells and inhibiting RORγt expression.