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Alterations of the Mice Gut Microbiome via Schistosoma japonicum Ova-Induced Granuloma.

ABSTRACT: Schistosomiasis, also called bilharziasis, is a neglected tropical disease induced by Schistosoma spp. that causes hundreds of millions of infections. Although Schistosoma ova-induced granulomas commonly cause inflammation, hyperplasia, ulceration, micro abscess formation, and polyposis, the role of the egg granuloma on the gut microbiome remains unclear. To explore the role, gut microbial communities in mice infected with Schistosoma japonicum were surveyed. Female C57BL/6 and BALB/c mice were exposed to cercariae of S. japonicum for 45 and 65 days and then sacrificed. Intestinal contents and feces were collected, DNA was extracted, and high-throughput 16S rRNA gene-based pyrosequencing was used to provide a comparative analysis of gut microbial diversity. The intestinal mucosal tissues were also examined. Histopathologic analysis demonstrated that the basic structure of the colonic mucosa was damaged by ova-induced granuloma. Regarding the gut microbiome, 2,578,303 good-quality sequences were studied and assigned to 25,278 Operational Taxonomic Units (OTUs) at a threshold of 97% similarity. The average number of OTUs for C57BL/6 and BALB/c were 545 and 530, respectively. At the phylum level, intestinal microbial communities were dominated by Firmicutes, Bacteroidetes, Proteobacteria, and Verrucomicrobia. Infection with S. japonicum modified bacterial richness in the fecal associated microbiota. Exposure significantly modified bacterial community composition among different groups. At the phylogenetic levels, LEfSe analysis revealed that several bacterial taxa were significantly associated with the S. japonicum-infected mice. The present results suggest that egg granulomas in the intestine influence differentiation of the gut microbial community under pathophysiological conditions. This result suggests that intestinal microbiome-based strategies should be considered for early diagnosis, clinical treatment, and prognosis evaluation of schistosomiasis.

SUBMITTER: Zhao Y

PROVIDER: S-EPMC6411663 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Alterations of the Mice Gut Microbiome via Schistosoma japonicum Ova-Induced Granuloma.

Zhao Yanqing Y Yang Shuguo S Li Bei B Li Wei W Wang Jue J Chen Zongyun Z Yang Jing J Tan Huabing H Li Jian J

Frontiers in microbiology 20190305

Schistosomiasis, also called bilharziasis, is a neglected tropical disease induced by Schistosoma spp. that causes hundreds of millions of infections. Although Schistosoma ova-induced granulomas commonly cause inflammation, hyperplasia, ulceration, micro abscess formation, and polyposis, the role of the egg granuloma on the gut microbiome remains unclear. To explore the role, gut microbial communities in mice infected with Schistosoma japonicum were surveyed. Female C57BL/6 ...[more]

PMID: 30891012

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Project description:Schistosoma japonicum (S. japonicum) is one of the etiological agents of schistosomiasis, a widespread zoonotic parasitic disease. However, the mechanism of the balanced co-existence between the host immune system and S. japonicum as well as their complex interaction remains unclear. In this study, 16S rRNA gene sequencing, combined with metagenomic sequencing approach as well as ultraperformance liquid chromatography-mass spectrometry metabolic profiling, was applied to demonstrate changes in the gut microbiome community structure during schistosomiasis progression, the functional interactions between the gut bacteria and S. japonicum infection in BALB/c mice, and the dynamic metabolite changes of the host. The results showed that both gut microbiome and the metabolites were significantly altered at different time points after the infection. Decrease in richness and diversity as well as differed composition of the gut microbiota was observed in the infected status when compared with the uninfected status. At the phylum level, the gut microbial communities in all samples were dominated by Firmicutes, Bacteroidetes, Proteobacteria, and Deferribacteres, while at the genus level, Lactobacillus, Lachnospiraceae NK4A136 group, Bacteroides, Staphylococcus, and Alloprevotella were the most abundant. After exposure, Roseburia, and Ruminococcaceae UCG-014 decreased, while Staphylococcus, Alistipes, and Parabacteroides increased, which could raise the risk of infections. Furthermore, LEfSe demonstrated several bacterial taxa that could discriminate between each time point of S. japonicum infection. Besides that, metagenomic analysis illuminated that the AMP-activated protein kinase (AMPK) signaling pathway and the chemokine signaling pathway were significantly perturbed after the infection. Phosphatidylcholine and colfosceril palmitate in serum as well as xanthurenic acid, naphthalenesulfonic acid, and pimelylcarnitine in urine might be metabolic biomarkers due to their promising diagnostic potential at the early stage of the infection. Alterations of glycerophospholipid and purine metabolism were also discovered in the infection. The present study might provide further understanding of the mechanisms during schistosome infection in aspects of gut microbiome and metabolites, and facilitate the discovery of new targets for early diagnosis and prognostic purposes. Further validations of potential biomarkers in human populations are necessary, and the exploration of interactions among S. japonicum, gut microbiome, and metabolites is to be deepened in the future.

Project description:BackgroundSchistosoma 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.MethodsThis 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.ResultsThe 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.ConclusionsThis 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.

Project description:IntroductionRecent evidence has demonstrated that the microbiome is a driver of the underlying pathophysiological mechanisms of respiratory disease. Studies have indicated that bacterial metabolites produced in the gut and lung can impact lung inflammation and immune cell activity, affecting disease pathology. Despite asthma being a disease with marked sex differences, experimental work linking microbiomes and asthma has not considered the sex variable.MethodsTo test the hypothesis that the lung and gut microbial composition impacts allergic lung inflammation in a sex-specific manner, we evaluated lung and gut microbiome alterations in a mouse model of allergic inflammation and assessed their association with lung function and inflammation phenotypes. For this, we exposed male and female adult C57BL/6J mice intranasally to 25 µg of a house dust mite extract mix (HDM) daily, or phosphate-buffered saline (PBS) as control, for 5 weeks (n = 4-6/group). DNA from fecal pellets collected before and after the 5-week treatment, and from lung tissue collected at endpoint, was extracted using the ZymoBIOMICS®-96 MagBead DNA Kit and analyzed to determine the 16S microbiome via Targeted Metagenomic Sequencing.ResultsThe HDM treatment induced a sex-specific allergic inflammation phenotype with significantly higher neutrophilia, lymphocytosis, inflammatory gene expression, and histopathological changes in females than males following exposure to HDM, but higher airway hyperresponsiveness (AHR) in males than females. In addition, sex-specific lung gene expression and associated pathways were identified HDM mix after challenge. These changes corresponded to sex-specific alterations in the gut microbiome, where the Firmicutes to Bacteroidetes ratio (F:B) was significantly reduced in fecal samples from only male mice after HDM challenge, and alpha diversity was increased in males, but decreased in females, after 5-weeks of HDM treatment.DiscussionOverall, our findings indicate that intranasal allergen challenge triggers sex-specific changes in both gut and lung microbiomes, and induces sex-specific lung inflammation, AHR, and lung inflammatory gene expression pathways, suggesting a contribution of the lung-gut axis in allergic airway disease.

Project description:BackgroundHepatic macrophages regulate liver granuloma formation and fibrosis caused by infection with Schistosoma japonicum, with the manner of regulation dependent on macrophage activation state. Interleukin (IL)-37 may have immunomodulatory effects on macrophages. However, whether IL-37 can affect liver granuloma formation and fibrosis by affecting the polarization of macrophages in S. japonicum infection remains unclear. The aim of this study was to investigate IL-37-affected macrophage polarization in liver granuloma formation and fibrosis in S. japonicum infection.MethodsAn enzyme-linked immunosorbent assay (ELISA) was used to detect the expression of IL-37 in the serum of patients with acute S. japonicum infection and in the serum of healthy people. Recombinant IL-37 (rIL-37), CPP-IgG2Fc-IL-37 and no CPP-IgG2Fc-IL-37 proteins were injected into S. japonicum-infected mice every 3 days for a total of 6 times from day 24 post infection onwards. Subsequently, ELISA, quantitative reverse transcription-PCR, fluorescence-activated cell sorting and western blot were used to analyze whether IL-37 inhibits the formation of liver granulomas and the development of liver fibrosis by regulating the phenotypic transition of macrophages. Finally, the three IL-37 proteins and SIS3, a Smad3 inhibitor, were co-cultured in mouse peritoneal macrophages to explore the mechanism underlying the promotion of the polarization of M0 macrophages to the M2 phenotype by IL-37.ResultsSerum IL-37 levels were upregulated in schistosomiasis patients, and this increased level of IL-37 protein apparently alleviated the liver granuloma of mice in infection models. It also could induce liver and peritoneal macrophages to polarize to the M2 phenotype in S. japonicum-infected mice. The S. japonicum-infected mice injected with CPP-IgG2Fc-IL-37 group exhibited the most obvious improvement in inflammatory reaction against the liver granuloma. The number and ratio of M2 macrophages in the liver and peritoneal cavity were significantly higher in the three IL-37 protein groups, especially in the CPP-IgG2Fc-IL-37 group, compared to the controls. Similar results were also found regarding liver function damage. IL-37 induced macrophage M2 polarization by promoting AMP-activated protein kinase (AMPK) phosphorylation in vitro. Among all groups, the activation of AMPK was most significant in the CPP-IgG2Fc-IL-37 group, and it was found that SMAD3 could enhance the anti-inflammatory function of IL-37.ConclusionsThe results show that IL-37 was able to promote the polarization of macrophages to the M2 phenotype, thereby inhibiting the development of schistosomiasis. In comparison to the rIL-37 protein, the CPP-IgG2Fc-IL-37 protein has the advantages of being effective in small doses and having fewer side effects and a better efficacy.

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Alterations of the Mice Gut Microbiome via Schistosoma japonicum Ova-Induced Granuloma.

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Alterations of the Mice Gut Microbiome via <i>Schistosoma japonicum</i> Ova-Induced Granuloma.

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