Dental Biofilm Microbiota Dysbiosis Is Associated With the Risk of Acute Graft-Versus-Host Disease After Allogeneic Hematopoietic Stem Cell Transplantation

Abstract

Acute graft-versus-host disease (aGVHD) is one of the major causes of death after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Recently, aGVHD onset was linked to intestinal microbiota (IM) dysbiosis. However, other bacterial-rich gastrointestinal sites, such as the mouth, which hosts several distinctive microbiotas, may also impact the risk of GVHD. The dental biofilm microbiota (DBM) is highly diverse and, like the IM, interacts with host cells and modulates immune homeostasis. We characterized changes in the DBM of patients during allo-HSCT and evaluated whether the DBM could be associated with the risk of aGVHD. DBM dysbiosis during allo-HSCT was marked by a gradual loss of bacterial diversity and changes in DBM genera composition, with commensal genera reductions and potentially pathogenic bacteria overgrowths. High Streptococcus and high Corynebacterium relative abundance at preconditioning were associated with a higher risk of aGVHD (67% vs. 33%; HR = 2.89, P = 0.04 and 73% vs. 37%; HR = 2.74, P = 0.04, respectively), while high Veillonella relative abundance was associated with a lower risk of aGVHD (27% vs. 73%; HR = 0.24, P < 0.01). Enterococcus faecalis bloom during allo-HSCT was observed in 17% of allo-HSCT recipients and was associated with a higher risk of aGVHD (100% vs. 40%; HR = 4.07, P < 0.001) and severe aGVHD (60% vs. 12%; HR = 6.82, P = 0.01). To the best of our knowledge, this is the first study demonstrating that DBM dysbiosis is associated with the aGVHD risk after allo-HSCT.

Long-Term Analysis of Resilience of the Oral Microbiome in Allogeneic Stem Cell Transplant Recipients

“…The decrease in oral bacterial diversity after SCT has been described by our group after autologous SCT [10] and by others in both adults and children in alloSCT and autoSCT patients [9,[14][15][16][31][32][33]. Most studies described a significant change in microbial composition directly after SCT.…”

“…Changes in microbiome composition did not coincide with oral chronic graft-versus-host disease. Heidrich et al also did not find an association between acute GVHD anywhere in the body and the microbiome [14]. However, they described a higher acute GVHD risk in patients with a domination of E. faecalis.…”

“…Most studies described a significant change in microbial composition directly after SCT. Changes in the oral microbiome were related to oral mucositis in adults [9,10,16,31,32] or to acute GVHD anywhere in the body in adult patients [14] or children [15]. Almost all the studies lack data on the recovery of the oral microbiome as these studies ended at three to four weeks after SCT.…”

“…It is considered a low pathogenic bacterium, but it is described to be a causative agent of systemic infections in hospitalized patients. Moreover, Ralstonia pickettii was associated with lower survival after SCT [14,36]. Olsenella is a Gram-positive, rod-shaped genus, first isolated from the oral cavity.…”

“…A number of studies described changes in the oral microbiome early after cancer treatment [9][10][11][12][13][14][15]. Several genera, including Staphylococcus and Enterococcus, and loss of microbiome diversity were associated with oral mucositis [9,10,12,16].…”