Intestinal pathophysiological abnormalities in steady state and after vaso‐occlusive crisis in murine sickle cell disease

Poplawska, Maria; Dutta, Dibyendu; Jayaram, Manjunath; Salifu, Moro O.; Chong, Ngee Sing; Lim, Seah H.

doi:10.1111/bjh.17889

Cited by 11 publications

(26 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…SCD patients exhibit increased abundance of Veillonella that correlated with the frequency of VOC [40], and reduced Alistipes and Pseudobutyrivibrio [41], that are producers of short-chain fatty acids (SCFAs) needed for intestinal health. Intestinal microbial density is also increased in SCD [38,42]. Changes in bacterial composition and density exacerbate the intestinal injury induced by VOC.…”

Section: Sickle Cell Diseasementioning

confidence: 99%

“…The end-result of the event is the adherence of the sickle erythrocytes to activated leukocytes immobilized on the endothelium, causing microvascular occlusion, vaso-occlusive crisis (VOC), and tissue ischemia. VOC, when involving the splanchnic vasculature, damages the intestinal epithelium [36], as indicated by the elevated serum iFABP levels in SCD [37,38], and increased intestinal permeability. The local hypoxemia may also be responsible for the altered intestinal microbial composition in SCD [39].…”

Section: Sickle Cell Diseasementioning

confidence: 99%

See 1 more Smart Citation

Intestinal barrier functions in hematologic and oncologic diseases

et al. 2023

Self Cite

View full text Add to dashboard Cite

The intestinal barrier is a complex structure that not only regulates the influx of luminal contents into the systemic circulation but is also involved in immune, microbial, and metabolic homeostasis. Evidence implicating disruption in intestinal barrier functions in the development of many systemic diseases, ranging from non-alcoholic steatohepatitis to autism, or systemic complications of intestinal disorders has increased rapidly in recent years, raising the possibility of the intestinal barrier as a potential target for therapeutic intervention to alter the course and mitigate the complications associated with these diseases. In addition to the disease process being associated with a breach in the intestinal barrier functions, patients with hematologic and oncologic diseases are particularly at high risks for the development of increased intestinal permeability, due to the frequent use of broad-spectrum antibiotics and chemoradiation. They also face a distinct challenge of being intermittently severely neutropenic due to treatment of the underlying conditions. In this review, we will discuss how hematologic and oncologic diseases are associated with disruption in the intestinal barrier and highlight the complications associated with an increase in the intestinal permeability. We will explore methods to modulate the complication. To provide a background for our discussion, we will first examine the structure and appraise the methods of evaluation of the intestinal barrier.

show abstract

Section: Sickle Cell Diseasementioning

confidence: 99%

Section: Sickle Cell Diseasementioning

confidence: 99%

Intestinal barrier functions in hematologic and oncologic diseases

et al. 2023

Self Cite

View full text Add to dashboard Cite

show abstract

“…Recent studies in sickle cell disease (SCD) in mice [76,77] and in humans [78,79] have highlighted the presence and the role of disrupted gut barrier functions in affecting the phenotypes of the disease. This has been associated with intestinal dysbiosis that is characterized by a lower abundance of Alistipes and Pseudobutyrivirio [80].…”

Section: Ongoing Fmt Studies In Patients With Hematologic and Oncolog...mentioning

confidence: 99%

Fecal Microbiota Transplant for Hematologic and Oncologic Diseases: Principle and Practice

Zerdan

Niforatos

Nasr

et al. 2022

Cancers

Self Cite

View full text Add to dashboard Cite

Understanding of the importance of the normal intestinal microbial community in regulating microbial homeostasis, host metabolism, adaptive immune responses, and gut barrier functions has opened up the possibility of manipulating the microbial composition to modulate the activity of various intestinal and systemic diseases using fecal microbiota transplant (FMT). It is therefore not surprising that use of FMT, especially for treating relapsed/refractory Clostridioides difficile infections (CDI), has increased over the last decade. Due to the complexity associated with and treatment for these diseases, patients with hematologic and oncologic diseases are particularly susceptible to complications related to altered intestinal microbial composition. Therefore, they are an ideal population for exploring FMT as a therapeutic approach. However, there are inherent factors presenting as obstacles for the use of FMT in these patients. In this review paper, we discussed the principles and biologic effects of FMT, examined the factors rendering patients with hematologic and oncologic conditions to increased risks for relapsed/refractory CDI, explored ongoing FMT studies, and proposed novel uses for FMT in these groups of patients. Finally, we also addressed the challenges of applying FMT to these groups of patients and proposed ways to overcome these challenges.

show abstract

“…This decrease in intestinal barrier integrity can ultimately lead to the translocation of bacterial products into circulation that may exacerbate chronic inflammation in SCD, contributing to worsened disease outcomes. Recent studies in SCD patients and mouse models have demonstrated gut dysbiosis, 7 , 10 elevated markers of intestinal barrier dysfunction 8 , 11 , 12 and protective effects of intestinal microbiome depletion. 9 , 13 , 14 , 15 , 16 In this study, we add to the growing body of evidence for a “leaky gut” phenotype in SCD.…”

Section: Introductionmentioning

confidence: 99%

Intestinal barrier dysfunction in murine sickle cell disease is associated with small intestine neutrophilic inflammation, oxidative stress, and dysbiosis

et al. 2023

View full text Add to dashboard Cite

The intestinal microbiome has emerged as a potential contributor to the severity of sickle cell disease (SCD). We sought to determine whether SCD mice exhibit intestinal barrier dysfunction, inflammation, and dysbiosis. Using the Townes humanized sickle cell mouse model, we found a 3‐fold increase in intestinal permeability as assessed via FITC‐dextran (4 kDa) assay in SS (SCD) mice compared to AA (wild type) mice ( n = 4, p < 0.05). This was associated with 25 to 50% decreases in claudin‐1, 3, and 15 and zonula occludens‐1 gene expression ( n = 8–10, p < 0.05) in the small intestine. Increased Ly6G staining demonstrated more neutrophils in the SS small intestine (3‐fold, n = 5, p < 0.05) associated with increased expression of TNFα, IL‐17A, CXCL1, and CD68 (2.5 to 5‐fold, n = 7–10, p < 0.05). In addition, we observed 30 to 55% decreases in superoxide dismutase‐1, glutathione peroxidase‐1, and catalase antioxidant enzyme expression ( n = 7–8, p < 0.05) concomitant to an increase in superoxide (2‐fold, n = 4, p < 0.05). Importantly, all significant observations of a leaky gut phenotype and inflammation were limited to the small intestine and not observed in the colon. Finally, characterization of the composition of the microbiome within the small intestine revealed dysbiosis in SS mice compared to their AA littermates with 47 phyla to species‐level significant alterations in amplicon sequence variants. We conclude that the intestinal barrier is compromised in SCD, associated with decreased gene expression of tight junction proteins, enhanced inflammation, oxidative stress, and gut microbiome dysbiosis, all specific to the small intestine.

show abstract

Intestinal pathophysiological abnormalities in steady state and after vaso‐occlusive crisis in murine sickle cell disease

Cited by 11 publications

References 18 publications

Intestinal barrier functions in hematologic and oncologic diseases

Intestinal barrier functions in hematologic and oncologic diseases

Fecal Microbiota Transplant for Hematologic and Oncologic Diseases: Principle and Practice

Intestinal barrier dysfunction in murine sickle cell disease is associated with small intestine neutrophilic inflammation, oxidative stress, and dysbiosis

Contact Info

Product

Resources

About