Protecting Intestinal Microenvironment Alleviates Acute Graft-Versus-Host Disease

Zhou, Zhengcan; Shang, Tao; Li, Xiurong; Zhu, Hongyan; Qi, Yubo; Zhao, Xin; Chen, Xi; Z, Shi; Pan, Guixiang; Wang, Yuefei; Fan, Guanwei; Gao, Xiumei; Zhu, Yan; Feng, Yi

doi:10.3389/fphys.2020.608279

Cited by 7 publications

(6 citation statements)

References 71 publications

(108 reference statements)

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“…An inhibitor of the stress protein HSP90 (17AAG) improves aGVHD by increasing the numbers of ISCs and Paneth cells, as well as the expression of defensins [74]. In a mouse aGVHD model, maintaining intestinal barrier integrity prevents the dysbiosis of intestinal microbial diversity and mitigates aGVHD [75]. Taken together, these studies indicate that the intestinal barrier plays a critical role in the pathophysiology of aGVHD.…”

Section: Intestinal Barrier and Agvhdmentioning

confidence: 99%

Roles of the intestinal microbiota and microbial metabolites in acute GVHD

Lin

et al. 2021

Exp Hematol Oncol

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Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is one of the most curative strategies for the treatment of many hematologic malignancies and diseases. However, acute graft-versus-host disease (GVHD) limits the success of allo-HSCT. The prevention and treatment of acute GVHD is the key issue for improving the efficacy of allo-HSCT and has become a research hotspot. The intestine is the primary organ targeted by acute GVHD, and the intestinal microbiota is critical for maintaining the homeostasis of the intestinal microenvironment and the immune response. Many studies have demonstrated the close association between the intestinal microbiota and the pathogenesis of acute GVHD. Furthermore, dysbiosis of the microbiota, which manifests as alterations in the diversity and composition of the intestinal microbiota, and alterations of microbial metabolites are pronounced in acute GVHD and associated with poor patient prognosis. The microbiota interacts with the host directly via microbial surface antigens or microbiota-derived metabolites to regulate intestinal homeostasis and the immune response. Therefore, intervention strategies targeting the intestinal microbiota, including antibiotics, prebiotics, probiotics, postbiotics and fecal microbiota transplantation (FMT), are potential new treatment options for acute GVHD. In this review, we discuss the alterations and roles of the intestinal microbiota and its metabolites in acute GVHD, as well as interventions targeting microbiota for the prevention and treatment of acute GVHD.

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Section: Intestinal Barrier and Agvhdmentioning

confidence: 99%

Roles of the intestinal microbiota and microbial metabolites in acute GVHD

Lin

et al. 2021

Exp Hematol Oncol

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“…H&E staining was conducted as described ( Zhou et al, 2021 ). Briefly, 24 h after CLP, the mice were euthanized by cervical dislocation, lung tissues were collected and fixed with 4% formalin, then dehydrated and paraffin embedded.…”

Section: Methodsmentioning

confidence: 99%

Xuebijing injection inhibited neutrophil extracellular traps to reverse lung injury in sepsis mice via reducing Gasdermin D

Shang

Zhang²,

Wang³

et al. 2022

Front. Pharmacol.

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The mortality of sepsis and septic shock remains high worldwide. Neutrophil extracellular traps (NETs) release is a major cause of organ failure and mortality in sepsis. Targeting Gasdermin D (GSDMD) can restrain NETs formation, which is promising for sepsis management. However, no medicine is identified without severe safety concerns for this purpose. Xuebijing injection (XBJ) has been demonstrated to alleviate the clinical symptoms of COVID-19 and sepsis patients, but there are not enough animal studies to reveal its mechanisms in depth. Therefore, we wondered whether XBJ relieved pulmonary damage in sepsis by suppressing NETs formation and adopted a clinically relevant polymicrobial infection model to test this hypothesis. Firstly, XBJ effectively reversed lung injury caused by sepsis and restrained neutrophils recruitment to lung by down-regulating proinflammatory chemokines, such as CSF-3, CXCL-2, and CXCR-2. Strikingly, we found that XBJ significantly reduced the expressions of NETs component proteins, including citrullinated histone H3 (CitH3), myeloperoxidase (MPO), and neutrophil elastase (NE). GSDMD contributes to the production of NETs in sepsis. Notably, XBJ exhibited a reduced effect on the expressions of GSDMD and its upstream regulators. Besides, we also revealed that XBJ reversed NETs formation by inhibiting the expressions of GSDMD-related genes. Collectively, we demonstrated XBJ protected against sepsis-induced lung injury by reversing GSDMD-related pathway to inhibit NETs formation.

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“…The details regarding the effects of the alterations in the gut microbiota on the prognosis of GVHD in HSCT patients are not clear. However, protecting the intestinal microenvironment might be a novel strategy to manage GVHD [50]. Additionally, the gut microbiota can modify the pharmacokinetics of cyclosporine [51].…”

Section: Future Perspectivesmentioning

confidence: 99%

Promising Tactics with Certain Probiotics for the Treatment of Nephropathy in Hematopoietic Stem Cell Transplantation

Taniguchi¹,

Sawamura²,

Ikeda³

et al. 2022

OBM Transplant

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Hematopoietic stem cell transplantation (HSCT) is a standard form of cellular therapy for patients suffering from malignant hematological diseases. However, graft-versus-host disease (GVHD) is a very serious complication and a major cause of morbidity and mortality after allogeneic HSCT. Calcineurin inhibitors, such as cyclosporine, are widely used to enhance the survival of patients who have undergone HSCT. Unfortunately, both GVHD and cyclosporine occasionally cause nephropathy. Several studies have shown that the gut-kidney axis is associated with nephropathy. Dysbiosis of the gut microbiota might aggravate renal damage by increasing systemic micro-inflammation, suggesting that diet might affect the risk of GVHD. Here, we summarized the recent findings regarding the association between the alteration of gut microbiota and nephrotoxicity. The results suggested that treatment with certain probiotics benefits the symbiosis in the gut-kidney axis and makes HSCT safer.

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Protecting Intestinal Microenvironment Alleviates Acute Graft-Versus-Host Disease

Cited by 7 publications

References 71 publications

Roles of the intestinal microbiota and microbial metabolites in acute GVHD

Roles of the intestinal microbiota and microbial metabolites in acute GVHD

Xuebijing injection inhibited neutrophil extracellular traps to reverse lung injury in sepsis mice via reducing Gasdermin D

Promising Tactics with Certain Probiotics for the Treatment of Nephropathy in Hematopoietic Stem Cell Transplantation

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