| Popis: |
Background. Acute Graft-versus-Host Disease (aGvHD) is the main complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Gut microbiota composition has been shown to contribute to aGvHD, however, the specific composition of the intestinal ecosystem involved in the pathologic process at the time of aGvHD onset is not yet fully known. Methods. A relevant series of allo-HSCT microbiome data sets were combined and reanalyzed, with focus on species level changes in the microbiota, using state-of-the-art and in part proprietary 16S analysis routines. Results. Immunosuppressive conditioning was found to impact gut microbiome (GM) composition. GM composition was found highly correlated with aGvHD status at onset (R2=0.4). The species diversity, average biological safety level (BSL), gram staining balance and the strict anaerobe proportion at aGvHD onset indicate that a moderate level of gram positive strict anaerobe cleansing with antibiotics reduces the risk of aGvHD. Butyrate producers were found associated with non-aGvHD controls, as well as the probiotic species and IL-10 inducer Bifidobacterium longum. Among species associated with mortality and aGvHD, we found Th1 and Th17 eliciting bacteria. We formulated a probiotic composition putatively competing with mortality and aGvHD species, from correlation analysis in a large superset of gut samples (n=17,800) from clinical- and crowd-sourced studies. Implications. To restore the Treg/Th17 balance, probiotic supplementation with B. longum eventually combined with Bacillus clausii, prebiotics and vitamin B9 is a treatment option. Simultaneous use of vancomycin, metronidazole, ceftazidime and rifaximin for GM control is a possibility, because of antibiotic resistance of B. longum. |
