scholarly journals Roles of the intestinal microbiota and microbial metabolites in acute GVHD

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Dandan Lin ◽  
Bo Hu ◽  
Pengfei Li ◽  
Ye Zhao ◽  
Yang Xu ◽  
...  

AbstractAllogeneic 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.

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Kucher M ◽  
Goloshchapov O ◽  
Suvorova M ◽  
Klementeva R ◽  
Shcherbakov A ◽  
...  

This short communication accompanies our presentation at the 43rd Annual meeting of the European Society for Blood and Marrow Transplantation held in Marseille, France, 26-29 March 2017. Also it briefly summaries some recent advances in fecal microbiota transplantation (FMT) for treatment of infections in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. AlloHSCT is an effective method of treatment for some hematological, malignant and hereditary conditions in adults and children. However, allo-HSCT is also associated with several potentially life-threatening complications. Among the most common causes for transplantassociated mortality are antibiotic-resistant bloodstream infections and immune complications, such as acute and chronic graft-versushost disease (GvHD). In most cases, gastrointestinal tract (GIT) is primarily damaged post-HSCT due to enhanced inflammation, GvHD, and intestinal infections causing serious diarrhea, in particular pseudomembranous colitis associated with Clostridium difficile, which often develops in patients receiving massive antibiotic therapy. Normal intestinal microbiota elimination is itself an important risk factor for sepsis, GIT GvHD, pseudo-membranous colitis and antibiotic-associated diarrhea post-HSCT. FMT from healthy donors allows restoring the physiological variability and functional activity of intestinal microbiota leading to pathogens eradication in patients with GIT infections.


Pathogens ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1550
Author(s):  
Stefania Pane ◽  
Maria Vittoria Ristori ◽  
Simone Gardini ◽  
Alessandra Russo ◽  
Federica Del Chierico ◽  
...  

A growing body of evidence shows that dysbiotic gut microbiota may correlate with a wide range of disorders; hence, the clinical use of microbiota maps and fecal microbiota transplantation (FMT) can be exploited in the clinic of some infectious diseases. Through direct or indirect ecological and functional competition, FMT may stimulate decolonization of pathogens or opportunistic pathogens, modulating immune response and colonic inflammation, and restoring intestinal homeostasis, which reduces host damage. Herein, we discuss how diagnostic parasitology may contribute to designing clinical metagenomic pipelines and FMT programs, especially in pediatric subjects. The consequences of more specialized diagnostics in the context of gut microbiota communities may improve the clinical parasitology and extend its applications to the prevention and treatment of several communicable and even noncommunicable disorders.


2021 ◽  
Vol 100 (3) ◽  
pp. 17-27
Author(s):  
O.V. Goloshchapov ◽  
◽  
A.B. Chukhlovin ◽  
E.A. Bakin ◽  
O.V. Stanevich ◽  
...  

In recent years, the important role of disturbances in the intestinal microbiota and its possible correction in children with oncological and autoimmune diseases has been established. The aim of the article is to review the literature data on the issue and to describe own experience of fecal microbiota transplantation (FMT) in children with an intestinal form of acute graftversus-host disease (GVHD). Materials and methods of research: a prospective single-center study included 7 patients aged 3 to 10 years with gut GVHD developed after transplantation of allogeneic hematopoietic stem cells (allo-HSCT). The clinical effects of FMT have been studied in children using rating scales during 120 days after this procedure. Time-dependent changes in the composition of fecal microbiota were assessed by the method of multiplex polymerase chain reaction test-system (PCR). Results: the literature data show a significant role of the content and ratio of of the main bacterial classes of Firmicutes and Bacteroides in the development of the immune response in cancer and autoimmune processes, as well as the possibility of correcting disorders using FMT. The first-hand experience of FMT in children with gut GVHD and antibiotic-resistant colitis is presented. Complete or partial response to GVHD therapy after 120 days was achieved in 6 (86%) patients in the absence of serious adverse events after FMT. From day +3 after FMT, increased amounts of B. fragilis gr., F. prausnitzii and E. coli were registered in fecal microbiota (p<0,048, p<0,001, p<0,048, respectively) in the absence of differences in Bifidobacterium spp. and Lactobacillus spp. Conclusion: the combination of systemic immunosuppressive therapy with FMT in patients with intestinal forms of GVHD resistant to standard therapy is accompanied by pronounced clinical responses and typical changes in the composition of the intestinal microbiota in the absence of serious adverse events.


Author(s):  
stefania pane ◽  
Maria Vittoria Ristori ◽  
simone gardini ◽  
alessandra russo ◽  
Federica Del Chierico ◽  
...  

A growing body of evidences is showing that dysbiotic gut microbiota may correlate with a wide range of disorders; hence, the clinical use of microbiota maps and fecal microbiota transplantation (FMT) can be exploited in the clinic of some infectious diseases. Through direct or indirect ecological and functional competition, FMT may stimulate decolonization of pathogens or opportunistic pathogens, modulating immune response and colonic inflammation, and restoring intestinal homeostasis, with reduction of host damage. Herein, we discuss how diagnostic parasitology may contribute to design clinical metagenomics pipelines and FMT programs, especially in pediatric subjects. The consequences of a more specialized diagnostics in the context of gut microbiota communities may improve the clinical parasitology and extend its applications to the prevention and treatment of several communicable and even noncommunicable disorders.


2021 ◽  
Vol 96 (4) ◽  
pp. 358-362
Author(s):  
Sang Hoon Yeon ◽  
Myung-Won Lee ◽  
Deog-Yeon Jo ◽  
Bu-Yeon Heo ◽  
Jaeyul Kwon ◽  
...  

Restoring the microbiota via fecal microbiota transplantation (FMT) can be an effective treatment for steroid-refractory acute graft-versus-host disease (GVHD) of the gut. Here, we report two adult patients who underwent FMT to treat steroid-refractory acute GVHD of the gut. The first patient was a 43-year-old man who underwent allogeneic hematopoietic stem cell transplantation (HSCT) with cells from a matched sibling donor. The second patient was a 70-year-old woman who underwent haplo-identical HSCT with cells from her son. Gut GVHD developed at 7 and 4 weeks after HSCT, respectively. After undergoing FMT, the clinical symptoms improved; the first patient had a complete response and the second patient had a partial response. Microbial analyses using RNA gene sequencing showed that a diverse fecal microbiome was recovered by 4 weeks after FMT. FMT should be considered an effective therapeutic option for managing steroid-refractory acute GVHD of the gut.


Author(s):  
Phillipp Hartmann ◽  
Bernd Schnabl

AbstractAlcohol-associated liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD) are important causes of morbidity and mortality worldwide. The intestinal microbiota is involved in the development and progression of both ALD and NAFLD. Here we describe associated changes in the intestinal microbiota, and we detail randomized clinical trials in ALD and NAFLD which evaluate treatments modulating the intestinal microbiome including fecal microbiota transplantation, probiotics, prebiotics, synbiotics, and antibiotics. Finally, we discuss precision medicine approaches targeting the intestinal microbiome to ameliorate ALD and NAFLD.


2019 ◽  
Vol 16 (1) ◽  
pp. 7-18 ◽  
Author(s):  
Svetlana G. Makarova ◽  
Leyla S. Namazova-Baranova ◽  
Oksana A. Ereshko ◽  
Dmitry S. Yasakov ◽  
Pavel E. Sadchikov

Intestinal microbiota is the factor that identifies considerably the human health. The impact of the microbial factor on a child begins long before his birth. Children have certain features in forming of immune response and intestinal microbiocenosis even before birth. Decline in diversity of intestinal microbiota is common in children with allergic disease even during first months of life, before allergic pathology development. Capabilities for microbiota development adjustment are sufficiently restricted. However it is clinically proven that early (within the first hours of life) breastfeeding attachment, breastfeeding itself within at least first 6 months of life, the use of prebiotics in milk formulas as well as the use of probiotics can give positive results on allergy management. In this review we present results of recent metaanalyses and consensus papers of international medical communities about use of probiotics and prebiotics in prevention and treatment of allergic diseases. Despite great scientific and practical interest to this topic, authors of metaanalyses bring our attention to the lack of evidence-based clinical trials.


2021 ◽  
Vol 12 ◽  
Author(s):  
Ma Liang ◽  
Zhang Liwen ◽  
Song Jianguo ◽  
Dai Juan ◽  
Ding Fei ◽  
...  

Intestinal microbiota (IM) dysbiosis contributes to the development of autoimmune hepatitis (AIH). This study aimed to investigate the potential effect of fecal microbiota transplantation (FMT) in a murine model of experimental AIH (EAH), a condition more similar to that of AIH patients. Changes in the enteric microbiome were determined in AIH patients and EAH mice. Moreover, we established an experimental model of secondary EAH mice harboring dysbiosis (ABx) to analyze the effects of therapeutic FMT administration on follicular regulatory T (TFR) and helper T (TFH) cell imbalances and IM composition in vivo. Alterations of the IM composition and bacterial translocation occurred in AIH patients compared to nonalcoholic fatty liver disease patients and healthy controls (HCs). Therapeutic FMT significantly attenuated liver injury and bacterial translocation and improved the imbalance between splenic TFR cells and TFH cells in ABx EAH mice. Furthermore, therapeutic FMT also partially reversed the increasing trend in serum liver enzymes (ALT and AST) of CXCR5−/−EAH mice on the 28th day. Finally, therapeutic FMT could effectively restore antibiotic-induced IM dysbiosis in EAH mice. Taken together, our findings demonstrated that FMT was capable of controlling hepatitis progression in EAH mice, and the associated mechanism might be involved in the regulation of the TFR/TFH immune imbalance and the restoration of IM composition.


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