Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0018133 (graft-versus-host disease)
 18,032 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A single nucleotide polymorphism (SNP) responsible for lactase persistence (LCT -13910C>T) changes intestinal microflora. Considering the influence of bacterial microflora on various immune effects, we tested DNA from 111 recipients/donors and analyzed whether this SNP interferes with survival and the incidence of acute graft-versus-host disease (aGVHD) after allogeneic hematopoetic stem cell transplantations (HSCT). Median overall survival (OS) was significantly longer when donors had a CC genotype (not reached after 133 vs 11.1 months, P = .004). Multivariate analysis identified a donor T allele (hazard ratio 2.63, 95% confidence interval 1.29-5.33, P = .008) as independent risk factor for death. Surprisingly, recipient genotypes did not influence outcome and there were no differences regarding aGVHD. Transplantation-related mortality (TRM), relapse and pneumonia were significantly less frequent in patients with CC donors. These findings add to the growing list of non-HLA polymorphisms with impact on outcome after allogeneic HSCT.
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PMID:A single nucleotide polymorphism at chromosome 2q21.3 (LCT -13910C>T) associates with clinical outcome after allogeneic hematopoietic stem cell transplantation. 2043 Sep 69

Graft versus host disease (GVHD) is a post-transplant pathology in which donor-derived T cells present in the Peyer's patches target the cell-surface alloantigens of the recipient, causing host tissue damages. Therefore, the GVHD has long been considered only a purely immunological process whose prevention requires an immunosuppressive treatment. However, since the early 2010s, the impact of gut microbiota on GVHD has received increased attention. Both a surprising fall in gut microbiota diversity and a shift toward Enterobacteriaceae were described in this disease. Recently, unexpected results were reported that further link GVHD with changes in bacterial composition in the gut and disruption of intestinal epithelial tight junctions leading to abnormal intestinal barrier permeability. Patients receiving allogenic hematopoietic stem cell transplant (allo-HCT) as treatment of hematologic malignancies showed a decrease of the overall diversity of the gut microbiota that affects Clostridia and Blautia spp. and a predominance of lactic acid bacteria (LAB) of the Enterococcus genus, in particular the lactose auxotroph Enterococcus faecium. The reduced microbiota diversity (likely including Actinobacteria, such as Bifidobacterium adolescentis that cross feed butyrogenic bacteria) deprives the butyrogenic bacteria (such as Roseburia intestinalis or Eubacterium) of their capacity to metabolize acetate to butyrate. Indeed, administration of butyrate protects against the GVHD. Here, we review the data highlighting the possible link between GVHD and lactase defect, accumulation of lactose in the gut lumen, reduction of Reg3 antimicrobial peptides, narrower enzyme equipment of bacteria that predominate post-transplant, proliferation of En. faecium that use lactose as metabolic fuels, induction of innate and adaptive immune response against these bacteria which maintains an inflammatory process, elevated expression of myosin light chain kinase 210 (MLCK210) and subsequent disruption of intestinal barrier, and translocation of microbial products (lactate) or transmigration of LAB within the liver. The analysis of data from the literature confirms that the gut microbiota plays a major role in the GVHD. Moreover, the most recent publications uncover that the LAB, butyrogenic bacteria and bacterial cross feeding were the missing pieces in the puzzle. This opens new bacteria-based strategies in the treatment of GVHD.
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PMID:The Butyrogenic and Lactic Bacteria of the Gut Microbiota Determine the Outcome of Allogenic Hematopoietic Cell Transplant. 3279 50