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Abstract The success of allogeneic hematopoietic cell transplantation (alloHCT) in curing hematologic disorders is limited by its short- and long-term toxicities. One such toxicity is oral mucositis (OM), causing pain, speech/swallowing difficulty, and prolonged hospitalization. Although conditioning chemoradiotherapy is the direct cause of OM, potential host-intrinsic mediators of mucosal injury remain elusive. We hypothesized that the oral microbiota may influence OM severity. We used a validated comprehensive scoring system based on specialized Oral Medicine examinations to longitudinally quantify OM severity in alloHCT recipients. High-throughput multi-site profiling of the oral microbiota was performed in parallel. We identify a sex-dependent commensal bacterium, Oribacterium asaccharolyticum, whose presence in saliva before transplantation is associated with more severe OM 14 days after transplantation. The sex predilection of this species correlated with higher uric acid levels in men. Our findings represent the first sex-dependent microbiota-mediated pathway in OM pathogenesis and introduce novel targets for preventative interventions.

ABSTRACTIn small series, third-party fecal microbiota transplantation (FMT) has been successful in decolonizing the gut from clinically relevant antibiotic resistance genes (ARGs). Less is known about the short- and long-term effects of FMT on larger panels of ARGs. We analyzed 226 pre- and post-treatment stool samples from a randomized placebo-controlled trial of FMT in 100 patients undergoing allogeneic hematopoietic cell transplantation or receiving anti-leukemia induction chemotherapy for 47 ARGs. These patients have heavy antibiotic exposure and a high incidence of colonization with multidrug-resistant organisms. Samples from each patient spanned a period of up to 9 months, allowing us to describe both short- and long-term effects of FMT on ARGs, while the randomized design allowed us to distinguish between spontaneous changes vs. FMT effect. We find an overall bimodal pattern. In the first phase (days to weeks after FMT), low-level transfer of ARGs largely associated with commensal healthy donor microbiota occurs. This phase is followed by long-term resistance to new ARGs as stable communities with colonization resistance are formed after FMT. The clinical implications of these findings are likely context-dependent and require further research. In the setting of cancer and intensive therapy, long-term ARG decolonization could translate into fewer downstream infections.

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Abstract The multitude of barriers between the mouth and colon may eliminate swallowed oral bacteria. Ascertaining the presence of the same bacteria in the mouth and colon is methodologically challenging partly because 16S rRNA gene sequencing – the most commonly used method to characterize the human microbiota – has low confidence in taxonomic assignments deeper than genus for most bacteria. As different species of the same genus can have low-level variation across the same 16S rRNA gene region, shotgun sequencing is needed to identify a true overlap. We analyzed a curated, multi-cohort, shotgun metagenomic database with species-level taxonomy and clade-specific marker genes to fill this knowledge gap. Using 500 paired fecal/oral (4 oral sites) samples from 4 healthy adult cohorts, we found a minute overlap between the two niches. Comparing marker genes between paired oral and fecal samples with species-level overlap, the pattern of overlap in only 7 individuals was consistent with same-strain colonization. These findings argue against ectopic colonization of oral bacteria in the distal gut in healthy adults.

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