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Background: Schistosomiasis is still one of the most serious parasitic diseases. Evidence showed that the metabolite profile in serum can potentially act as a marker for parasitic disease diagnosis and evaluate disease progression and prognosis. However, the serum metabolome in patients with Schistosoma japonicum infection is not well defined. In this study, we investigated the metabolite profiles of patients with chronic and with advanced S. japonicum infection., Methods: The sera of 33 chronic S. japonicum patients, 15 patients with advanced schistosomiasis and 17 healthy volunteers were collected. Samples were extracted for metabolites and analyzed with ultra-performance liquid chromatography-mass spectrometry (UPLC-MS)., Results: We observed significant differences in metabolite profiles in positive and negative ion modes between patients with advanced and chronic S. japonicum infection. In patients with chronic S. japonicum infection, 199 metabolites were significantly upregulated while 207 metabolites were downregulated in advanced infection. These differential metabolites were mainly concentrated in steroid hormone biosynthesis, cholesterol metabolism and bile secretion pathways. We also found that certain bile acid levels were significantly upregulated in the progression from chronic to advanced S. japonicum infection. In receiver operator characteristic (ROC) analysis, we identified three metabolites with area under the curve (AUC) > 0.8, including glycocholic (GCA), glycochenodeoxycholate (GCDCA) and taurochenodeoxycholic acid (TCDCA) concentrated in cholesterol metabolism, biliary secretion and primary bile acid biosynthesis., Conclusions: This study provides evidence that GCA, GCDCA and TCDCA can potentially act as novel metabolite biomarkers to distinguish patients in different stages of S. japonicum infection. This study will contribute to the understanding of the metabolite mechanisms of the transition from chronic to advanced S. japonicum infection, although more studies are needed to validate this potential role and explore the underlying mechanisms., (© 2024. The Author(s).)

This study intends to use the basic information and blood routine of schistosomiasis patients to establish a machine learning model for predicting liver fibrosis. We collected medical records of Schistosoma japonicum patients admitted to a hospital in China from June 2019 to June 2022. The method was to screen out the key variables and six different machine learning algorithms were used to establish prediction models. Finally, the optimal model was compared based on AUC, specificity, sensitivity and other indicators for further modeling. The interpretation of the model was shown by using the SHAP package. A total of 1049 patients' medical records were collected, and 10 key variables were screened for modeling using lasso method, including red cell distribution width-standard deviation (RDW-SD), Mean corpuscular hemoglobin concentration (MCHC), Mean corpuscular volume (MCV), hematocrit (HCT), Red blood cells, Eosinophils, Monocytes, Lymphocytes, Neutrophils, Age. Among the 6 different machine learning algorithms, LightGBM performed the best, and its AUCs in the training set and validation set were 1 and 0.818, respectively. This study established a machine learning model for predicting liver fibrosis in patients with Schistosoma japonicum. The model could help improve the early diagnosis and provide early intervention for schistosomiasis patients with liver fibrosis., (© 2024. The Author(s).)

Background: Schistosomiasis, a neglected tropical disease, remains an important public health problem. Although there are various methods for diagnosing schistosomiasis, many limitations still exist. Early diagnosis and treatment of schistosomiasis can significantly improve survival and prognosis of patients., Methodology: Circulating cell-free (cf)DNA has been widely used in the diagnosis of various diseases. In our study, we evaluated the diagnostic value of circulating cfDNA for schistosomiasis caused by Schistosoma japonicum. We focused on the tandem sequences and mitochondrial genes of S. japonicum to identify highly sensitive and specific targets for diagnosis of Schistosomiasis japonica., Results: Through data screening and analysis, we ultimately identified four specific tandem sequences (TD-1, TD-2, TD-3. and TD-4) and six mitochondrial genes (COX1(1), COX1(2), CYTB, ATP6, COX3, and ND5). We designed specific primers to detect the amount of circulating cfDNA in S. japonicum-infected mouse and chronic schistosomiasis patients. Our results showed that the number of tandem sequences was significantly higher than that of the mitochondrial genes. A S. japonicum infection model in mice suggested that infection of S. japonicum can be diagnosed by detecting circulating cfDNA as early as the first week. We measured the expression levels of circulating cfDNA (TD-1, TD-2, and TD-3) at different time points and found that TD-3 expression was significantly higher than that of TD-1 or TD-2. We also infected mice with different quantities of cercariae (20 s and 80 s). The level of cfDNA (TD-3) in the 80 s infection group was significantly higher than in the 20 s infection group. Additionally, cfDNA (TD-3) levels increased after egg deposition. Meanwhile, we tested 42 patients with chronic Schistosomiasis japonica and circulating cfDNA (TD-3) was detected in nine patients., Conclusions: We have screened highly sensitive targets for the diagnosis of Schistosomiasis japonica, and the detection of circulating cfDNA is a rapid and effective method for the diagnosis of Schistosomiasis japonica. The levels of cfDNA is correlated with cercariae infection severity. Early detection and diagnosis of schistosomiasis is crucial for patient treatment and improving prognosis., (© 2024. The Author(s).)

Background: Schistosoma infection is a significant public health issue, affecting over 200 million individuals and threatening 700 million people worldwide. The species prevalent in China is Schistosoma japonicum. Recent studies showed that both gut microbiota and metabolome are closely related to schistosomiasis caused by S. japonicum, but clinical study is limited and the underlying mechanism is largely unclear. This study aimed to explore alterations as well as function of gut microbiota and metabolite profile in the patients with S. japonicum infection., Methods: This study included 20 patients diagnosed with chronic schistosomiasis caused by S. japonicum, eight patients with advanced schistosomiasis caused by S. japonicum and 13 healthy volunteers. The fresh feces of these participators, clinical examination results and basic information were collected. 16S ribosomal RNA gene sequencing was used to investigate gut microbiota, while ultraperformance liquid chromatography-mass spectrometry (UHPLC-MS) was applied to explore the metabolome of patients in different stages of schistosomiasis., Results: The study found that gut microbiota and metabolites were altered in patients with different stages of S. japonicum infection. Compared with healthy control group, the gut microbial diversity in patients with chronic S. japonicum infection was decreased significantly. However, the diversity of gut microbiota in patients with chronic schistosomiasis was similar to that in patients with advanced schistosomiasis. Compared with uninfected people, patients with schistosomiasis showed decreased Firmicutes and increased Proteobacteria. As disease progressed, Firmicutes was further reduced in patients with advanced S. japonicum infection, while Proteobacteria was further increased. In addition, the most altered metabolites in patients with S. japonicum infection were lipids and lipid-like molecules as well as organo-heterocyclic compounds, correlated with the clinical manifestations and disease progress of schistosomiasis caused by S. japonicum., Conclusions: This study suggested that the gut microbiota and metabolome altered in patients in different stages of schistosomiasis, which was correlated with progression of schistosomiasis caused by S. japonicum. This inter-omics analysis may shed light on a better understanding of the mechanisms of the progression of S. japonicum infection and contribute to identifying new potential targets for the diagnosis and prognosis of S. japonicum infection. However, a large sample size of validation in clinic is needed, and further study is required to investigate the underlying mechanism., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Immune cells are important for the development of schistosomiasis japonica and are also critical for the treatment of schistosomiasis. The immune cells in the peripheral blood help assess the immune state. The peripheral lymphocytes in schistosomiasis mansoni were well studied; however, immune cells in patients with different stages of schistosomiasis japonica are not well analysed. Here, we performed a preliminary study to explore characteristics of peripheral lymphocyte subsets in patients with different stages of schistosomiasis japonica. 135 patients with Schistosoma japonicum infection and 25 healthy volunteers were included in this study, including 84 patients with chronic S. japonicum infection and 51 patients with advanced S. japonicum infection. Flow cytometry analysis was performed to evaluate peripheral lymphocytes including T cells, B cells, and natural killer (NK) cells. Blood routine and liver function test data were analysed. Ultrasound examination was used to access liver fibrosis according to the World Health Organization standard about ultrasound in schistosomiasis. Demographic data analysis suggested there was no difference in age and gender in patients with S. japonicum infection and health control group. Liver function tests showed that patients with advanced schistosomiasis had a higher incidence of liver function abnormality and blood lipid than those with chronic schistosomiasis. Blood routine results reflected that haemoglobin, red blood cells, platelets, as well as lymphocytes in the advanced group were significantly less than that in the chronic group. Furthermore, flow cytometry analysis indicated that the percentage of CD4 + T cells was lower in the advanced group, but the percentage of CD19 + B cells was higher in the advanced group. In addition, the number of CD3 + T cells, CD3 + CD4 + T cells, CD3 + CD8 + T cells, and NK cells was less in the advanced group when compared with those in the chronic group. In addition, there was a correlation between the decrease in CD4 + T cells and more severe fibrosis on ultrasound images. Our results indicated that the immune state in the peripheral is different in different stages of S. japonicum infection. Lymphocyte subset analysis has potential to facilitate differential diagnosis of different stages of schistosomiasis japonica and even to be a prognostic factor., (© 2023 John Wiley & Sons Ltd.)

Introduction: Liver fibrosis is a poor outcome of patients with schistosomiasis, impacting the quality of life and even survival. Eggs deposited in the liver were the main pathogenic factors of hepatic fibrosis in Schistosomiasis japonica. However, the mechanism of hepatic fibrosis in schistosomiasis remains not well defined and there is no effective measure to prevent and treat schistosome-induced hepatic fibrosis., Methods: In this study, we applied single-cell sequencing to primarily explore the mechanism of hepatic fibrosis in murine schistosomiasis japonica (n=1) and normal mouse was served as control (n=1)., Results: A total of 10,403 cells were included in our analysis and grouped into 18 major cell clusters. Th2 cells and NKT cells were obviously increased and there was a close communication between NKT cells and FASLG signaling pathway. Flow cytometry analysis indicated that the expression of Fasl in NKT cells, CD8+ T cell and NK cell were higher in SJ groups. Arg1 , Retnla and Chil3 , marker genes of alternatively activated macrophages (M2), were mainly expressed in mononuclear phagocyte(1) (MP(1)), suggesting that Kupffer cells might undergo M2-like polarization in fibrotic liver of schistosomiasis. CXCL and CCL signaling pathway analysis with CellChat showed that Cxcl16-Cxcr6, Ccl6-Ccr2 and Ccl5-Ccr5 were the most dominant L-R and there were close interactions between T cells and MPs., Conclusion: Our research profiled a preliminary immunological network of hepatic fibrosis in murine schistosomiasis japonica, which might contribute to a better understanding of the mechanisms of liver fibrosis in schistosomiasis. NKT cells and CXCL and CCL signaling pathway such as Cxcl16-Cxcr6, Ccl6-Ccr2 and Ccl5-Ccr5 might be potential targets to alleviate hepatic fibrosis of schistosomiasis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhang, Li, Li, Jiang, Guo, Zhou, Zhou and Ming.)

Background: Schistosoma japonicum infection is an important public health problem, imposing heavy social and economic burdens in 78 countries worldwide. However, the mechanism of transition from chronic to advanced S. japonicum infection remains largely unknown. Evidences suggested that gut microbiota plays a role in the pathogenesis of S. japonicum infection. However, the composition of the gut microbiota in patients with chronic and advanced S. japonicum infection is not well defined. In this study, we compared the composition of the intestinal flora in patients with chronic and advanced S. japonicum infection., Methods: The feces of 24 patients with chronic S. japonicum infection and five patients with advanced S. japonicum infection from the same area were collected according to standard procedures, and 16S rRNA sequencing technology was used to analyze the intestinal microbial composition of the two groups of patients., Results: We found that alteration occurs in the gut microbiota between the groups of patients with chronic and advanced S. japonicum infections. Analysis of alpha and beta diversity indicated that the diversity and abundance of intestinal flora in patients with advanced S. japonicum infection were lower than those in patients with chronic S. japonicum infection. Furthermore, Prevotella 9, Subdoligranulum, Ruminococcus torques, Megamonas and Fusicatenibacter seemed to have potential to discriminate different stages of S. japonicum infection and to act as biomarkers for diagnosis. Function prediction analysis revealed that microbiota function in the chronic group was focused on translation and cell growth and death, while that in the advanced group was concentrated on elevating metabolism-related functions., Conclusions: Our study demonstrated that alteration in gut microbiota in different stages of S. japonicum infection plays a potential role in the pathogenesis of transition from chronic to advanced S. japonicum infection. However, further validation in the clinic is needed, and the underlying mechanism requires further study., (© 2022. The Author(s).)

Background: Liver fibrosis is thought to have a close relationship with lipid profile. The possible association between lipids and liver fibrosis of different etiologies has been widely explored. However, the association between lipids and liver fibrosis in patients infected with Schistosoma japonicum remains unclear. In the present study we undertook a preliminary exploration of the association between lipid profile and liver fibrosis, and developed a new predictive index for liver fibrosis in S. japonicum-infected patients., Methods: A total of 1503 patients diagnosed with S. japonicum at Xiangyue Hospital, China were enrolled in this retrospective study. The patients were divided into two groups, i.e., those with and those without liver fibrosis, by two experienced schistosomiasis specialists, according to the results of liver ultrasound examination. Demographic, clinical, and laboratory data were collected. Multivariable logistic models were used to estimate the independent associations between lipid profile and liver fibrosis. Receiver operating characteristic (ROC) curves were used to assess the discriminative ability of the new index in predicting liver fibrosis in patients with schistosomiasis., Results: Logistic regression analysis showed that high-density lipoprotein (HDL) [adjusted odds ratio (aOR), 95% confidence interval (CI) 7.334, 5.051-10.649; P < 0.001], low-density lipoprotein (LDL) (aOR, 95% CI 0.434, 0.370-0.509; P < 0.001), hemoglobin (HB) (aOR, 95% CI 0.979, 0.971-0.987; P < 0.001) and platelets (PLT) (aOR, 95% CI 0.996, 0.994-0.999; P < 0.001) were independently associated with liver fibrosis in patients with schistosomiasis. ROC analysis indicated that the combination of HDL, LDL and HB levels [(HDL × 100)/(LDL × HB)] had a higher area under the ROC curve (AUC = 0.773), and thus may better predict liver fibrosis than the aspartate transaminase-to-platelet ratio index (AUC = 0.608) and fibrosis index based on four factors (AUC = 0.624)., Conclusions: To the best of our knowledge, this is the first study to report that HDL, LDL, HB and PLT levels are independently associated with liver fibrosis in patients with schistosomiasis. (HDL × 100)/(LDL × HB) outperformed the aspartate transaminase-to-platelet ratio index and fibrosis index based on four factors in terms of ROC, and thus could be a new predictive index for liver fibrosis. These findings may help clinicians to more easily and effectively diagnose liver fibrosis in patients with schistosomiasis., (© 2022. The Author(s).)

Background: Organ transplantation is currently an effective method for treating organ failure. Long-term use of immunosuppressive drugs has huge side effects, which severely restricts the long-term survival of patients. Schistosoma can affect the host's immune system by synthesizing, secreting, or excreting a variety of immunomodulatory molecules, but its role in transplantation was not well defined. In order to explore whether Schistosoma -related products can suppress rejection and induce long-term survival of the transplant, we used soluble egg antigen (SEA) of Schistosoma japonicum in mouse skin transplantation models., Materials and Methods: Each mouse was intraperitoneally injected with 100 μg of SEA three times a week for four consecutive weeks before allogenic skin transplant. Skin transplants were performed on day 0 to observe graft survival. Pathological examination of skin grafts was conducted 7 days post transplantation. The skin grafts were subjected to mRNA sequencing. Bioinformatics analysis was conducted and the expression of hub genes was verified by qPCR. Flow cytometry analysis was performed to evaluate the immune status and validate the results from bioinformatic analysis., Results: The mean survival time (MST) of mouse skin grafts in the SEA-treated group was 11.67 ± 0.69 days, while that of the control group was 8.00 ± 0.36 days. Pathological analysis showed that Sj SEA treatment led to reduced inflammatory infiltration within skin grafts 7 days after allogenic skin transplantation. Bioinformatics analysis identified 86 DEGs between the Sj SEA treatment group and the control group, including 39 upregulated genes and 47 downregulated genes. Further analysis revealed that Sj SEA mediated regulation on cellular response to interferon-γ, activation of IL-17 signaling and chemokine signaling pathways, as well as cytokine-cytokine receptor interaction. Flow cytometry analysis showed that SEA treatment led to higher percentages of CD4 + IL-4 + T cells and CD4 + Foxp3 + T cells and decreased CD4 + IFN-γ + T cells in skin transplantation., Conclusion: Sj SEA treatment suppressed rejection and prolonged skin graft survival by regulating immune responses. Sj SEA treatment might be a potential new therapeutic strategy to facilitate anti-rejection therapy and even to induce tolerance., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Jiang, Li, Zhang, Zhou, Guo, Zhou, Ming.)

Schistosomiasis is a widespread helminth disease that poses a heavy social and economic burden on people worldwide. Advanced schistosomiasis often develops into schistosome-associated liver fibrosis, the pathogenesis of which remains unclear. This study aimed preliminarily to profile immune cells of schistosome-associated liver fibrosis using single-cell RNA sequencing. Three patient groups were enrolled, including an Schistosomiasis japonicum (SJ) group (n = 1), a chronic liver failure (CLF) group (n = 3) and a healthy control (HC) group (n = 2), revealing 17 cell clusters out of 20 093 cells. From these limited datasets, it was observed that T cell(1), mononuclear phagocytes-1 and dendritic cells (DCs) were higher in the SJ group. CAVIN2 + MP(2) was the predominant cell type in the MP subset of the SJ group (53%), and was higher than that in both the CLF (8%) and HC (1%) groups. Kupffer cell marker genes (CD163, MARCO and TIMD4) were enriched in caveolae-associated protein 2 (CAVIN2) + MP(2), which was also an important source of TGFB1. The KEGG pathways of CAVIN2 + MP(2) indicated that they were associated with lysosome, endocytosis, phagosome and antigen processing and presentation. The preliminary study showed that granzyme B (GZMB) + T cell(1) and ankyrin repeat domain-containing protein 36B + T cell(3) were the most common T cells in the SJ group (50% and 32%, respectively). The KEGG pathways of GZMB + T cell(1) were mainly related to natural killer cell-mediated cytotoxicity. The percentage of ring1 and YY1 binding protein (RYBP) + DC(1) was higher in the SJ group (57%) than in the CLF (16%) and HC (6%) groups. The KEGG pathway of RYBP + DC(1) was related to Fc gamma R-mediated phagocytosis and antigen processing and presentation. Overall, CAVIN2 + Kupffer cells were the main source of TGFB1, consisting primarily of mononuclear phagocytes in the livers of the SJ group subjects and potentially playing an irreplaceable role in hepatic fibrosis of schistosomiasis., (© 2021 The Authors. Immunology & Cell Biology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc.)

The parasites and eggs of helminths, including schistosomes, are associated with factors that can modulate the nature and outcomes of host immune responses, particularly enhancing type 2 immunity and impairing the effects of type 1 and type 17 immunity. The main species of schistosomes that cause infection in humans are capable of generating a microenvironment that allows survival of the parasite by evasion of the immune response. Schistosome infections are associated with beneficial effects on chronic immune disorders, including allergies, autoimmune diseases, and alloimmune responses. Recently, there has been increasing research interest in the role of schistosomes in immunoregulation during human infection, and the mechanisms underlying these roles continue to be investigated. Further studies may identify potential opportunities to develop new treatments for immune disease. In this review, we provide an update on the advances in our understanding of schistosome-associated modulation of the cells of the innate and adaptive immune systems as well as the potential role of schistosome-associated factors as therapeutic modulators of immune disorders, including allergies, autoimmune diseases, and transplant immunopathology. We also discuss potential opportunities for targeting schistosome-induced immunoregulation for future translation to the clinical setting., (Copyright © 2020 American Society for Microbiology.)

Background: Schistosoma japonicum (S. japonicum) is the main species of Schistosoma prevalent in China. Myeloid-derived suppressor cells (MDSCs) are important immunoregulatory cells and generally expand in parasite infection, but there is little research relating to MDSCs in Schistosoma infection. Methods: Fifty-six S. japonicum-infected patients were included in this study. MDSCs and percentages and absolute cell numbers of lymphocyte subsets, including CD3+ T cells, CD4+ T cells, CD8+ T cells, B cells and natural killer (NK) cells were detected using flow cytometry. The degree of liver fibrosis was determined using color Doppler ultrasound. Results: Patients infected with S. japonicum had a much higher percentage of MDSCs among peripheral blood mononuclear cells (PBMCs) than the healthy control. Regarding subpopulations of MDSCs, the percentage of granulocytic myeloid-derived suppressor cells (G-MDSCs) was clearly increased. Correlation analysis showed that the absolute cell counts of T-cell subsets correlated negatively with the percentages of MDSCs and G-MDSCs among PBMCs. The percentage of G-MDSCs in PBMCs was also significantly higher in patients with liver fibrosis diagnosed by color doppler ultrasound (grade > 0), and the percentage of G-MDSCs in PBMCs and liver fibrosis grading based on ultrasound showed a positive correlation. Conclusion: S. japonicum infection contributes to an increase in MDSCs, especially G-MDSCs, whose proliferation may inhibit the number of CD4+ T cells in peripheral blood. Meanwhile, there is a close relationship between proliferation of G-MDSCs and liver fibrosis in S. japonicum-infected patients.

Correction to: Parasites & Vectors (2022) 15:268 https://doi.org/10.1186/s13071-022-05359... Following publication of the original article [[1]], the authors flagged an error in the legend of Fig. Reference 1 Liu Y, Zhang P, Li J, Li H, Zhou C, Zhang Y, Ming Y. Association between serum lipid profile and liver fibrosis in patients infected with Schistosoma japonicum. [Extracted from the article]