Exosomes secreted by Blastocystis subtypes affect the expression of proinflammatory and anti-inflammatory cytokines (TNFα, IL-6, IL-10, IL-4)

Norouzi, Mojtaba; Pirestani, Majid; Arefian, Ehsan; Dalimi, Abdolhossein; Sadraei, Javid; Mirjalali, Hamed

doi:10.3389/fmed.2022.940332

Cited by 5 publications

(5 citation statements)

References 51 publications

(49 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Notably, we elucidate the characteristics of a “Low-grade symptoms cluster” where specific microorganisms may play a role in the regulation of the immune response through diverse mechanisms. Blastocystis sp., subtype 1, exhibits the ability to modulate pro and anti-inflammatory cytokines via exosomes (Norouzi et al, 2022). Dialister sp.…”

Section: Discussionmentioning

confidence: 99%

Non-responsive Celiac disease symptoms associated with microbiome network structure and function

Marcos-Zambrano,

Lacruz-Plegezuelos,

Valdés

et al. 2023

Preprint

View full text Add to dashboard Cite

Non-responsive celiac disease (NRCD) poses a challenge for clinicians due to the persistence of symptoms despite maintaining a gluten-free diet (GFD). This study investigated the gut microbiome, mucosal integrity, and metabolomic profiles of 39 NRCD patients to gain insights into the underlying mechanisms contributing to symptom persistence. Two distinct clusters of patients were identified based on clinical and demographic variables not influenced by gluten consumption. Cluster 1, labelled "Low-grade symptoms," displayed milder symptoms and lower inflammatory markers. In contrast, Cluster 2, named "High-grade symptoms," exhibited more severe gastrointestinal and extraintestinal symptoms, along with elevated inflammatory markers and increased intestinal permeability. Despite similar mucosal damage in both clusters, network analysis of the gut microbiome revealed specific microbial taxa with potential functional implications. Cluster 1 displayed a microbiome associated with immune homeostasis and gut barrier integrity, potentially lowering inflammation and symptom severity. In contrast, Cluster 2 had a distinct microbiome linked to lactate production, Th17 activation, possibly contributing to heightened inflammation and gastrointestinal symptoms. Metabolomic analysis revealed differential metabolites between clusters, particularly in amino acid metabolism pathways. Metabolites associated with specific symptoms were identified, implicating their potential role in symptom manifestation. Notably, vitamin D deficiency was observed in both clusters, suggesting its relevance in the context of NRCD. The study highlights the importance of the gut microbiome, mucosal integrity, and metabolic pathways in symptom persistence among NRCD patients. The associations between microbial-derived metabolites and symptom severity provide valuable insights into potential therapeutic targets. Further research is needed to validate these findings and develop targeted interventions for improving clinical outcomes in NRCD patients.

show abstract

Section: Discussionmentioning

confidence: 99%

Non-responsive Celiac disease symptoms associated with microbiome network structure and function

Marcos-Zambrano,

Lacruz-Plegezuelos,

Valdés

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…Emerging evidence suggests that even molecules lacking signal peptides are secreted in EVs, particularly via exosomes. EVs might promote parasite establishment and modulate immune responses; CPs have been identified as cargos of EVs of Blastocystis , Entamoeba and Giardia but not Cryptosporidium [ 31 , 165 , 166 ]. This is now a promising field for future work.…”

Section: Discussionmentioning

confidence: 99%

“…within extracellular vesicles as it occurs in other intestinal protozoa such as G. duodenalis [ 31 ] and E. histolytica [ 165 ]. Blastocystis STs 1–3 secrete exosomes (30–100 nm sized) that, when added to human leukemia monocytic cells (THP-1 line), caused different effects on the expression of proinflammatory (IL-6 and TNF-α) and anti-inflammatory (IL-4 and IL-10) cytokines: ST1 upregulated IL-6 and TNF-α concomitant to IL-4 and IL-10 downregulation, ST2/ST3 downregulated IL-10 and ST3 upregulated IL-6 [ 166 ]. Taken together, all of these data provide insights into the important roles of Blastocystis ´ CPs contributing to immunopathological responses such as urticaria and bowel inflammation observed in some patients [ 167 ] and leading to immune evasion and modulation that promotes colonization and persistence of Blastocystis in susceptible hosts ( Figure 4 B).…”

Section: Blastocystis Cysteine Proteases: From Subtypes To P...mentioning

confidence: 99%

Extracellular Cysteine Proteases of Key Intestinal Protozoan Pathogens—Factors Linked to Virulence and Pathogenicity

Argüello-García

Carrero

Ortega-Pierres

2023

IJMS

View full text Add to dashboard Cite

Intestinal diseases caused by protistan parasites of the genera Giardia (giardiasis), Entamoeba (amoebiasis), Cryptosporidium (cryptosporidiosis) and Blastocystis (blastocystosis) represent a major burden in human and animal populations worldwide due to the severity of diarrhea and/or inflammation in susceptible hosts. These pathogens interact with epithelial cells, promoting increased paracellular permeability and enterocyte cell death (mainly apoptosis), which precede physiological and immunological disorders. Some cell-surface-anchored and molecules secreted from these parasites function as virulence markers, of which peptide hydrolases, particularly cysteine proteases (CPs), are abundant and have versatile lytic activities. Upon secretion, CPs can affect host tissues and immune responses beyond the site of parasite colonization, thereby increasing the pathogens’ virulence. The four intestinal protists considered here are known to secrete predominantly clan A (C1- and C2-type) CPs, some of which have been characterized. CPs of Giardia duodenalis (e.g., Giardipain-1) and Entamoeba histolytica (EhCPs 1-6 and EhCP112) degrade mucin and villin, cause damage to intercellular junction proteins, induce apoptosis in epithelial cells and degrade immunoglobulins, cytokines and defensins. In Cryptosporidium, five Cryptopains are encoded in its genome, but only Cryptopains 4 and 5 are likely secreted. In Blastocystis sp., a legumain-activated CP, called Blastopain-1, and legumain itself have been detected in the extracellular medium, and the former has similar adverse effects on epithelial integrity and enterocyte survival. Due to their different functions, these enzymes could represent novel drug targets. Indeed, some promising results with CP inhibitors, such as vinyl sulfones (K11777 and WRR605), the garlic derivative, allicin, and purified amoebic CPs have been obtained in experimental models, suggesting that these enzymes might be useful drug targets.

show abstract

“…All stool samples were examined for the presence of intestinal parasites using direct microscopy. The presence of Blastocystis in stool samples was confirmed using amplification of the “barcoding region” through the small subunit ribosomal RNA ( SSU rRNA ) gene [ 22 ]. The presence of any other cysts/oocysts/eggs in stool samples was considered as exclusion criteria.…”

Section: Methodsmentioning

confidence: 99%

Profiling of the fecal microbiota and circulating microRNA-16 in IBS subjects with Blastocystis infection : a case–control study

Olyaiee,

Yadegar,

Mirsamadi

et al. 2023

Eur J Med Res

Self Cite

View full text Add to dashboard Cite

Irritable bowel syndrome (IBS) is a prevalent gastrointestinal (GI) tract disorder. Although the main reason for IBS is not clear, the interaction between intestinal microorganisms and the gut barrier seems to play an important role in pathogenesis of IBS. The current study aimed to investigate the effect of Blastocystis on the gut microbiota profile and the circulation levels of microRNA (mir)-16 of IBS patients compared to healthy subjects. Stool and blood samples were collected from 80 participants including 40 samples from each IBS and healthy group. Upon DNA extraction from stool samples, barcoding region and quantitative real-time PCR were analyzed to investigate Blastocystis and the microbiota profile, respectively. RNA was extracted from serum samples of included subjects and the expression of mir-16 was evaluated using stem-loop protocol and qreal-time PCR. Significant changes between IBS patients and healthy controls was observed in Firmicutes, Actinobacteria, Faecalibacterium, and Alistipes. In IBS patients, the relative abundance of Bifidobacteria was directly correlated with the presence of Blastocystis, while Alistipes was decreased with Blastocystis. Lactobacillus was significantly increased in Blastocystis carriers. In healthy subjects, the relative abundance of Bifidobacteria was decreased, but Alistipes was increased in Blastocystis carriers. The changes in the Firmicutes/Bacteroidetes ratio was not significant in different groups. The relative expression of mir-16 in Blastocystis-negative IBS patients and healthy carriers was significantly overexpressed compared to control group. The presence of Blastocystis, decreased the relative expression of mir-16 in IBS patients compared to Blastocystis-negative IBS patients. The present study revealed that Blastocystis has the ability to change the abundance of some phyla/genera of bacteria in IBS and healthy subjects. Moreover, Blastocystis seems to modulate the relative expression of microRNAs to control the gut atmosphere, apply its pathogenicity, and provide a favor niche for its colonization.

show abstract

Exosomes secreted by Blastocystis subtypes affect the expression of proinflammatory and anti-inflammatory cytokines (TNFα, IL-6, IL-10, IL-4)

Cited by 5 publications

References 51 publications

Non-responsive Celiac disease symptoms associated with microbiome network structure and function

Non-responsive Celiac disease symptoms associated with microbiome network structure and function

Extracellular Cysteine Proteases of Key Intestinal Protozoan Pathogens—Factors Linked to Virulence and Pathogenicity

Profiling of the fecal microbiota and circulating microRNA-16 in IBS subjects with Blastocystis infection : a case–control study

Contact Info

Product

Resources

About