Allogenic stem cell transplant-associated acute graft versus host disease: a computational drug discovery text mining approach using oral and gut microbiome signatures.

PURPOSE: Acute graft versus host disease (aGVHD) is a major cause of non-relapse morbidity and mortality post-allogenic hematopoietic stem cell transplant (HSCT). Using conventional literature search and computational approaches, our objective was to identify oral and gut bacterial species associated with aGVHD, potentially affecting drug treatment via lipopolysaccharide (LPS) pathways. METHODS: Medline, PubMed, PubMed Central, and Google Scholar were searched using MeSH terms. The top 100 hits per database were curated, and 25 research articles were selected to examine oral and gut microbiomes associated with health, HSCT, and aGVHD. Literature search validation, aGVHD drug targets, and microbial metabolic pathway identification were completed using BioReader, MACADAM, KEGG, and STRING programs. RESULTS: Our review determined that (1) oral genera Rothia, Solobacterium, and Veillonella were identified in HSCT patients' stool and associated with aGVHD; (2) shifts in gut enterococci profiles were determined in HSCT-associated aGVHD; (3) gut microbiome dysbiosis prior or during HSCT and lower Shannon diversity index at time of HSCT were also associated with increased risk of aGVHD and transplant related death; and (4) Coriobacteriaceae family was negatively correlated with gut aGVHD, whereas Eubacterium limosum was associated with decreased risk of chronic GVHD relapse. Additionally, we identified molecular pathways related to TLR4/ LPS, including candidate aGVHD drug targets, impacted by oral and gut bacterial taxa. CONCLUSION: Reduced microbial diversity reflects higher severity and mortality rate in HSCT patients with aGVHD. Multi-omics approaches to decipher oral and gut microbiome associations will be critical for developing aGVHD preventive therapies.

Porphyromonas gingivalis is the most abundant species detected in coronary and femoral arteries.

An association between oral bacteria and atherosclerosis has been postulated. A limited number of studies have used 16S RNA gene sequencing-based metagenomics approaches to identify bacteria at the species level from atherosclerotic plaques in arterial walls. The objective of this study was to establish detailed oral microbiome profiles, at both genus and species level, of clinically healthy coronary and femoral artery tissues from patients with atherosclerosis. Tissue specimens were taken from clinically non-atherosclerotic areas of coronary or femoral arteries used for attachment of bypass grafts in 42 patients with atherosclerotic cardiovascular disease. Bacterial DNA was sequenced using the MiSeq platform, and sequence reads were screened in silico for nearly 600 oral species using the HOMINGS ProbeSeq species identification program. The number of sequence reads matched to species or genera were used for statistical analyses. A total of 230 and 118 species were detected in coronary and femoral arteries, respectively. Unidentified species detected by genus-specific probes consisted of 45 and 30 genera in coronary and in femoral artery tissues, respectively. Overall, 245 species belonging to 95 genera were detected in coronary and femoral arteries combined. The most abundant species were Porphyromonas gingivalis, Enterococcus faecalis, and Finegoldia magna based on species probes. Porphyromonas, Escherichia, Staphylococcus, Pseudomonas, and Streptococcus genera represented 88.5% mean relative abundance based on combined species and genus probe detections. Porphyromonas was significantly more abundant than Escherichia (i.e. 46.8% vs. 19.3%; p = 0.0005). This study provides insight into the presence and types of oral microbiome bacterial species found in clinically non-atherosclerotic arteries.