# Investigating the oral microbiome in hematopoietic cell transplants

> **NIH NIH R03** · RESEARCH INST NATIONWIDE CHILDREN'S HOSP · 2024 · $170,746

## Abstract

ABSTRACT
While hematopoietic cell transplant (HCT) is an effective curative treatment for children with various malignant
and non-malignant diseases, it is also associated with several complications, such as oral mucositis (OM) and
bloodstream infections (BSI). The loss of mucosal integrity in OM not only results in ulcerative lesions that are a
significant source of pain, but also, the compromised mucosal barrier becomes susceptible to bacterial
translocation and predisposes patients to BSI. Several studies have reported disruptions of the oral microbiome
in patients undergoing HCT, and this was linked to OM. In addition, bacterial species present in the oral cavity
(i.e., viridans group streptococci) have been implicated in BSI. While this establishes the role of oral microbial
species in OM and BSI pathogenesis, nearly all of this research is limited to adults, despite the high prevalence
of OM (70-80%) and BSI (15-65%) in children. Furthermore, the current standard for diagnosing BSI is culture-
based method that is not comprehensive or high enough resolution to distinguish all species, including the oral
streptococci. It is crucial to accurately define the blood microbial signature of this high-risk cohort to determine if
the oral cavity is a reservoir of organisms causing BSI, and if so, to guide preventive approaches. For Aim 1 we
will conduct a longitudinal study in children undergoing HCT at Nationwide Children’s Hospital to understand the
impact of oral microbial species during the development and progression of OM and BSI. Our pilot study revealed
overall microbial community composition changed as children underwent HCT. We will now expand our sample
size to define the oral microbial community changes at the species level and determine the relationship of these
changes to oral mucositis and bloodstream infections. Site-specific oral samples (plaque, tongue, mucosa) will
be collected at a minimum of four time points. Both species level bacterial and fungal composition by 16S/ITS2
amplicon sequencing, and absolute abundance by qPCR will be analyzed. OM incidence and severity will be
scored, and all BSI occurrences will be recorded. The relationship of microbial community composition with time
course, oral hygiene, OM score, and BSI occurrence will be examined. Our preliminary 16S amplicon data
revealed polymicrobial profiles containing microbial species common to the oral cavity in the bloodstream of
subjects with BSI. For Aim 2 we will comprehensively define the bloodstream microbial profile in children
receiving HCT by longitudinally collecting blood samples from all subjects and comparing their bloodstream
microbial profile in the presence and absence of BSI. To determine if the oral cavity is the likely source of
bloodstream infection-associated microbes, we will use high-resolution bioinformatic tools (DADA2) on our
amplicon data and analyze the concordance of species detected in blood samples with those detected in the
oral cavity....

## Key facts

- **NIH application ID:** 10951639
- **Project number:** 1R03DE034037-01
- **Recipient organization:** RESEARCH INST NATIONWIDE CHILDREN'S HOSP
- **Principal Investigator:** Kyulim Lee
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $170,746
- **Award type:** 1
- **Project period:** 2024-08-12 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10951639

## Citation

> US National Institutes of Health, RePORTER application 10951639, Investigating the oral microbiome in hematopoietic cell transplants (1R03DE034037-01). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10951639. Licensed CC0.

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