Gut Microbiota and Transcriptomics Reveal the Effect of Human Norovirus Bioaccumulation on Oysters (Crassostrea gigas).

Human norovirus (HuNoV) is a major foodborne pathogen that causes acute viral gastroenteritis, and oysters are one of the main carriers of HuNoV transmission. While progress has been made toward understanding the pattern of oyster-bioaccumulated HuNoV, the response of oysters to HuNoV bioaccumulation, including changes in gene expression and gut microbiota, is unclear. In this study, histo-blood group antigen (HBGA)-like molecule expression and gene regulation features and the HuNoV-microbiome interactions of oysters during HuNoV bioaccumulation were characterized. With the prolongation of bioaccumulation time, the HuNoV content and expression of type A HBGA-like molecules in oysters increased and stabilized. HuNoV also altered the expression of immunity- and glycosphingolipid biosynthesis-related genes. Prolonged bioaccumulation of HuNoV can reduce the abundance and change the composition of the oyster gut microbiota. In particular, with the extension of bioaccumulation time, the abundance of Blautia, Agathobacter, Faecalibacterium, Terrisporobacter, Bifidobacterium, Lactobacillus, and Ruminococcus decreased, while the abundance of Vibrio and Alphaproteobacteria increased. This study provides potential candidates for identifying functional genes involved in the bioaccumulation of HuNoV in oysters. More importantly, it provides the first description of the changes in gut microbiota during HuNoV bioaccumulation in oysters. IMPORTANCE The role of the oyster gut microbiota in HuNoV bioaccumulation is poorly understood. This study revealed, for the first time, the changes in gut microbiota and gene expression of oysters with HuNoV bioaccumulation. This study enriches the understanding of the impact of HuNoV bioaccumulation on oysters and provides a new direction for the study of the molecular mechanism of HuNoV bioaccumulation in oysters.

Contamination, bioaccumulation mechanism, detection, and control of human norovirus in bivalve shellfish: A review.

Human norovirus (HuNoV) is a major foodborne pathogen that causes acute viral gastroenteritis, and bivalve shellfish are one of the main carriers of HuNoV transmission. A comprehensive understanding of bivalve shellfish-related HuNoV outbreaks focusing on contamination factors, bioaccumulation mechanisms, and pre- and post-harvest interventions is essential for the development of effective strategies to prevent contamination of shellfish. This review comprehensively surveys the current knowledge on global contamination and non-thermal treatment of HuNoV in bivalve shellfish. HuNoV contamination in bivalve shellfish is significantly related to the season and water. While evaluating the water quality of shellfish-inhabited waters is a key intervention, the development of non-heat treatment technology to effectively inactivate the HuNoV in bivalve shellfish while maintaining the flavor and nutrition of the shellfish is also an important direction for further research. Additionally, this review explores the bioaccumulation mechanisms of HuNoV in bivalve shellfish, especially the mechanism underlying the binding of histo-blood group antigen-like molecules and HuNoV. The detection methods for infectious HuNoV are also discussed. The establishment of effective methods to rapidly detect infectious HuNoV and development of biological components to inactivate or prevent HuNoV contamination in shellfish also need to be studied further.

Asparaginyl endopeptidase enhances pancreatic ductal adenocarcinoma cell invasion in an exosome-dependent manner and correlates with poor prognosis.

Pancreatic cancer is one of the most lethal types of cancer; owing to low early detection rates and high metastasis rates, it is associated with an extremely poor prognosis. Therefore, a better understanding of the molecular mechanisms that underlie its metastasis and the identification of potential prognostic biomarkers are urgently required. Although high expression levels of asparaginyl endopeptidase (AEP) have been detected in various types of solid tumor, the expression and functions of AEP in pancreatic carcinomas have yet to be determined. The present study aimed to examine the putative functions of AEP in pancreatic carcinoma. Immunohistochemical analysis revealed that AEP was highly expressed in pancreatic cancer tissues compared with adjacent normal tissues. Patients with high AEP expression exhibited a significantly shorter overall survival time. Results from multivariate Cox regression analysis revealed that AEP was an independent prognostic factor for overall survival. Gain- and loss-of-function experiments demonstrated that knockdown of AEP expression significantly reduced the invasive ability of pancreatic cancer cells, whereas overexpression of AEP increased the invasive ability. In addition, AEP was detected in exosomes that were derived from cultured pancreatic ductal adenocarcinoma cells (PDACs) and in the serum from patients with PDAC. The Matrigel-Transwell invasion assay revealed that exosomes enriched with AEP were able to enhance the invasive ability of PDAC cells, whereas exosomes lacking AEP decreased the invasive ability. Furthermore, results from the present study suggested that AEP may be crucial for activation of the phosphoinositide 3-kinase/RAC­α serine/threonine-protein kinase signaling pathway in PDAC cells. The present study data indicated that high AEP expression may be important for pancreatic carcinoma progression in an exosome-dependent manner, and that AEP may be an independent indicator of poor prognosis in patients with PDAC and may be a novel prognostic biomarker or therapeutic target in pancreatic carcinoma.