Dataset Information

Bile Ductal Transcriptome Identifies Key Pathways and Hub Genes in Clonorchis sinensis-Infected Sprague-Dawley Rats.

ABSTRACT: Clonorchis sinensis is a food-borne trematode that infects more than 15 million people. The liver fluke causes clonorchiasis and chronical cholangitis, and promotes cholangiocarcinoma. The underlying molecular pathogenesis occurring in the bile duct by the infection is little known. In this study, transcriptome profile in the bile ducts infected with C. sinensis were analyzed using microarray methods. Differentially expressed genes (DEGs) were 1,563 and 1,457 at 2 and 4 weeks after infection. Majority of the DEGs were temporally dysregulated at 2 weeks, but 519 DEGs showed monotonically changing expression patterns that formed seven distinct expression profiles. Protein-protein interaction (PPI) analysis of the DEG products revealed 5 sub-networks and 10 key hub proteins while weighted co-expression network analysis (WGCNA)-derived gene-gene interaction exhibited 16 co-expression modules and 13 key hub genes. The DEGs were significantly enriched in 16 Kyoto Encyclopedia of Genes and Genomes pathways, which were related to original systems, cellular process, environmental information processing, and human diseases. This study uncovered a global picture of gene expression profiles in the bile ducts infected with C. sinensis, and provided a set of potent predictive biomarkers for early diagnosis of clonorchiasis.

SUBMITTER: Yoo WG

PROVIDER: S-EPMC7672232 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Bile Ductal Transcriptome Identifies Key Pathways and Hub Genes in Clonorchis sinensis-Infected Sprague-Dawley Rats.

Yoo Won Gi WG Kang Jung-Mi JM Lê Huong Giang HG Pak Jhang Ho JH Hong Sung-Jong SJ Sohn Woon-Mok WM Na Byoung-Kuk BK

The Korean journal of parasitology 20201022 5

Clonorchis sinensis is a food-borne trematode that infects more than 15 million people. The liver fluke causes clonorchiasis and chronical cholangitis, and promotes cholangiocarcinoma. The underlying molecular pathogenesis occurring in the bile duct by the infection is little known. In this study, transcriptome profile in the bile ducts infected with C. sinensis were analyzed using microarray methods. Differentially expressed genes (DEGs) were 1,563 and 1,457 at 2 and 4 weeks after infection. Ma ...[more]

PMID: 33202503

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Project description:Clonorchiasis is an infectious disease caused by helminths of Clonorchis sinensis (C. sinensis). The adult parasite mainly inhabits the bile duct and gall bladder, and results in various complications to the hepatobiliary system. The amount of bile secreted into the intestine is reduced in cases of C. sinensis infection, which may alter the pH of the gut and decrease the amount of surfactant protein D released from the gallbladder. However, the impact of parasitic infection on the human gut microbiome remains unclear. To this end, we examined the gut microbiota composition in 47 modified Kato-Katz thick smear-positive (egg-positive) volunteers and 42 healthy controls from five rural communities. Subjects were grouped into four sub-populations based on age and infection status. High-throughput 16S rRNA gene sequencing revealed significant changes in alpha diversity between EP1 and EN1. The beta diversity showed alterations between C. sinensis-infected subjects and healthy controls. In C. sinensis infected patients, we found the significant reduction of certain taxa, such as Bacteroides and anti-inflammatory Bifidobacterium (P < 0.05). Bacteroides, a predominant gut bacteria in healthy populations, was negatively correlated with the number of C. sinensis eggs per gram (EPG, r = -0.37, P adjust < 0.01 in 20-60 years old group; r = -0.64, P adjust = 0.04 in the 60+ years old group). What's more, the reduction in the abundance of Bifidobacterium, a common probiotic, was decreased particularly in the 60 + years old group (r = -0.50, P = 0.04). The abundance of Dorea, a potentially pro-inflammatory microbe, was higher in infected subjects than in healthy individuals (P < 0.05). Variovorax was a unique bacteria that was only detected in infected subjects. These results clearly demonstrate the significant influence of C. sinensis infection on the human gut microbiota and provided new insights into the control, prevention, diagnosis, and clinical study of clonorchiasis through the human gut microbiota.

Project description:BackgroundAnisakiasis is an emerging public health problem, caused by Anisakis spp. nematode larvae. Anisakiasis presents as variable and unspecific gastrointestinal and/or allergic clinical symptoms, which accounts for the high rate of misdiagnosed cases.Methodology/principal findingsThe aim of this study was to characterize the early cellular (6-72 h p.i.) and molecular (6 h p.i.) immune response and general underlying regulatory mechanism in Anisakis infected rats. Each Sprague-Dawley rat was infected with 10 Anisakis spp. larvae by gastric intubation. Tissues with visible lesions were processed for: i) classic histopathology (HE), immunofluorescence (CD3, iNOS, S100A8/A9), and transmission electron microscopy (TEM); ii) target genes (Il1b, Il6, Il18, Ccl3, Icam1, Mmp9) and microRNA (Rat Immunopathology MIRN-104ZF plate, Quiagen) expression analysis; and iii) global DNA methylation. Histopathology revealed that Anisakis larval migration caused moderate to extensive hemorrhages in submucosal and epimysial/perimysial connective tissue. In stomach and muscle, moderate to abundant mixed inflammatory infiltrate was present, dominated by neutrophils and macrophages, while only mild infiltration was seen in intestine. Lesions were characterized by the presence of CD3+, iNOS+, and S100A8/A9+ cells. The greatest number of iNOS+ and S100A8/A9+ cells was seen in muscle. Il6, Il1b, and Ccl3 showed particularly strong expression in stomach and visceral adipose tissues, but the order of expression differed between tissues. In total, three miRNAs were differentially expressed, two in stomach (miRNA-451 and miRNA-223) and two in intestine (miRNA-451 and miRNA-672). No changes in global DNA methylation were observed in infected tissues relative to controls.Conclusions/significanceAnisakis infection induces strong immune responses in infected rats with marked induction of specific proinflammatory cytokines and miRNA expression. Deciphering the functional role of these cytokines and miRNAs will help in understanding the anisakiasis pathology and controversies surrounding Anisakis infection in humans.

Dataset Information

Bile Ductal Transcriptome Identifies Key Pathways and Hub Genes in Clonorchis sinensis-Infected Sprague-Dawley Rats.

Publications

Bile Ductal Transcriptome Identifies Key Pathways and Hub Genes in Clonorchis sinensis-Infected Sprague-Dawley Rats.

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