The role of the host gut microbiome in the pathophysiology of schistosomiasis

Stark, Klara A; Rinaldi, Gabriel; Cortés, Alba; Costain, Alice; MacDonald, Andrew S.; Cantacessi, Cinzia

doi:10.1111/pim.12970

Cited by 8 publications

(3 citation statements)

References 98 publications

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“…Moreover, eggs alter gut microbiota in both quantitative and qualitative ways ( 58 ). This underscores the pivotal role of the host’s gut microbiota in the crosstalk between schistosomes and host immunity, highlighting the possibility of host dysbiosis as a third partner in the disease process ( 59 ). Notably, gut dysbiosis contributes to the vascular inflammation of mesenteric venules ( 60 ), and recent evidence linking gut dysbiosis and alterations in purinergic signaling has emerged ( 61 ).…”

Section: Discussionmentioning

confidence: 92%

P2Y2-P2X7 receptors cross-talk in primed mesenteric endothelial cells upregulates NF-κB signaling favoring mononuclear cell adhesion in schistosomiasis

Oliveira,

Monteiro,

Mainieri

et al. 2024

Front. Immunol.

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Schistosomiasis is an intravascular infectious disease that impacts over 200 million people globally. In its chronic stage, it leads to mesenteric inflammation with significant involvement of monocytes/macrophages. Endothelial cells lining the vessel lumens play a crucial role, and mount of evidence links this disease to a downregulation of endoprotective cell signaling favoring a primed and proinflammatory endothelial cell phenotype and therefore the loss of immunovascular homeostasis. One hallmark of infectious and inflammatory conditions is the release of nucleotides into the extracellular milieu, which, in turn, act as innate messengers, activating purinergic receptors and triggering cell-to-cell communication. ATP influences the progression of various diseases through P2X and P2Y purinergic receptor subtypes. Among these receptors, P2Y2 (P2Y2R) and P2X7 (P2X7R) receptors stand out, known for their roles in inflammation. However, their specific role in schistosomiasis has remained largely unexplored. Therefore, we hypothesized that endothelial P2Y2R and P2X7R could contribute to monocyte adhesion to mesenteric endothelial cells in schistosomiasis. Using a preclinical murine model of schistosomiasis associated with endothelial dysfunction and age-matched control mice, we showed that endothelial P2Y2R and P2X7R activation increased monocyte adhesion to cultured primary endothelial cells in both groups. However, a distinct upregulation of endothelial P2Y2R-driven canonical Ca2+ signaling was observed in the infected group, amplifying adhesion. In the control group, the coactivation of endothelial P2Y2R and P2X7R did not alter the maximal monocyte adhesion induced by each receptor individually. However, in the infected group, this coactivation induced a distinct upregulation of P2Y2R-P2X7R-driven canonical signaling, IL-1β release, and VCAM-1 expression, with underlying mechanisms involving inflammasome and NF-κB signaling. Therefore, current data suggest that schistosomiasis alters endothelial cell P2Y2R/P2X7R signaling during inflammation. These discoveries advance our understanding of schistosomiasis. This intricate interplay, driven by PAMP-triggered endothelial P2Y2R/P2X7R cross-talk, emerges as a potential key player in the mesenteric inflammation during schistosomiasis.

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Section: Discussionmentioning

confidence: 92%

P2Y2-P2X7 receptors cross-talk in primed mesenteric endothelial cells upregulates NF-κB signaling favoring mononuclear cell adhesion in schistosomiasis

Oliveira,

Monteiro,

Mainieri

et al. 2024

Front. Immunol.

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“…Given that a high microbial alpha diversity is generally considered as an indicator of a ‘healthy’ gut [ 40 , 41 ], findings from this and previous studies [ 22 , 23 , 39 , 42 , 43 ] suggest that schistosome infections exert a negative impact on the homeostasis of the gut microbiota of rodent hosts. In humans, microbial alpha diversity was significantly reduced in faeces from infected children from Côte d'Ivoire [ 44 ] , whilst the microbiota of Kenyan children showed no diversity changes linked to S. mansoni infection when compared to uninfected controls (reviewed by [ 45 ]). Variability across human populations and study designs may account for these discrepancies [ 46 ].…”

Section: Resultsmentioning

confidence: 99%

Gut microbiota and immune profiling of microbiota-humanised versus wildtype mouse models of hepatointestinal schistosomiasis

Stark,

Rinaldi,

Costain

et al. 2024

anim microbiome

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Mounting evidence of the occurrence of direct and indirect interactions between the human blood fluke, Schistosoma mansoni, and the gut microbiota of rodent models raises questions on the potential role(s) of the latter in the pathophysiology of hepatointestinal schistosomiasis. However, substantial differences in both the composition and function between the gut microbiota of laboratory rodents and that of humans hinders an in-depth understanding of the significance of such interactions for human schistosomiasis. Taking advantage of the availability of a human microbiota-associated mouse model (HMA), we have previously highlighted differences in infection-associated changes in gut microbiota composition between HMA and wildtype (WT) mice. To further explore the dynamics of schistosome-microbiota relationships in HMA mice, in this study we (i) characterize qualitative and quantitative changes in gut microbiota composition of a distinct line of HMA mice (D2 HMA) infected with S. mansoni prior to and following the onset of parasite egg production; (ii) profile local and systemic immune responses against the parasite in HMA as well as WT mice and (iii) assess levels of faecal inflammatory markers and occult blood as indirect measures of gut tissue damage. We show that patent S. mansoni infection is associated with reduced bacterial alpha diversity in the gut of D2 HMA mice, alongside expansion of hydrogen sulphide-producing bacteria. Similar systemic humoral responses against S. mansoni in WT and D2 HMA mice, as well as levels of faecal lipocalin and markers of alternatively activated macrophages, suggest that these are independent of baseline gut microbiota composition. Qualitative comparative analyses between faecal microbial profiles of S. mansoni-infected WT and distinct lines of HMA mice reveal that, while infection-induced alterations of the gut microbiota composition are highly dependent on the baseline flora, bile acid composition and metabolism may represent key elements of schistosome-microbiota interactions through the gut-liver axis.

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“…However, there is evidence suggesting that the immune response of the host to Schistosoma eggs deposited in the appendix may play a role in generating granulomas. This reaction may diminish mucosal immunity, thus leading to elevating vulnerability to bacterial infections and the onset of acute appendicitis [ 8 – 10 ].…”

Section: Discussionmentioning

confidence: 99%

Schistosomal appendicitis: a case report

Khalifa,

Elhassan,

Abdel Rahim

2024

J Med Case Reports

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Background Schistosomiasis is one of the endemic parasitic diseases in many developing countries. Despite this, appendicitis secondary to schistosomiasis is an uncommon condition even in some endemic areas. Schistosomal appendicitis, an incidentally discovered appendicitis associated with schistosomiasis histological findings, affects young males predominantly. Timely diagnosis and treatment, including appendectomy and anti-helminthic therapy, are crucial. Case report A 24-year-old Sudanese male patient presented with abdominal pain. Diagnosed with acute appendicitis, he underwent appendectomy, revealing appendix inflammation with Schistosoma ova in histopathology. Abdominal ultrasound detected no complications. Weakly positive Schistosoma serology was noted, but stool and urine analysis showed no infection evidence. Prescribed praziquantel, patient had 3-year post-op follow-up without complications. Conclusions This case report underscores the significance of including schistosomiasis in the differential diagnosis of appendicitis, particularly in regions where the disease is endemic. It underscores the necessity of histopathological evaluations for accurate diagnosis, emphasizing the potential implications for clinical practice in similar settings.

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The role of the host gut microbiome in the pathophysiology of schistosomiasis

Cited by 8 publications

References 98 publications

P2Y2-P2X7 receptors cross-talk in primed mesenteric endothelial cells upregulates NF-κB signaling favoring mononuclear cell adhesion in schistosomiasis

P2Y2-P2X7 receptors cross-talk in primed mesenteric endothelial cells upregulates NF-κB signaling favoring mononuclear cell adhesion in schistosomiasis

Gut microbiota and immune profiling of microbiota-humanised versus wildtype mouse models of hepatointestinal schistosomiasis

Schistosomal appendicitis: a case report

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