# The Role of Brain-Oral-Microbiome Axis in Adverse Childhood Experiences-associated Dental Caries in Children

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2024 · $236,250

## Abstract

PROJECT SUMMARY/ABSTRACT
Adverse childhood experiences (ACEs), traumatic experiences encountered during early life stages, can
profoundly impact health and well-being into adulthood. ACE prevalence is high, with one in three children having
at least one ACE. Children belonging to racial or ethnic minority groups are disproportionately affected by ACEs.
Several health issues in children are strongly associated with ACEs, including asthma, sleep disturbances,
infection risk, obesity, and behavioral issues. Additionally, children with multiple ACEs are at high risk of dental
caries and untreated oral health care needs, even those with access to preventive dental care. The objective of
this study is to investigate the possible biological factors underlying ACE-associated dental caries, with the
overall goal of mitigating caries disparity in children with early-life adversity.
 ACEs function as biological stressors that affect neuroendocrine–immune (NEI) system responses. Recently,
the brain–gut–microbiome axis, describing the bidirectional, biochemical interactions of the gut microbiome with
the NEI system, was identified as a potential root cause of ACE-associated health conditions. Dental caries is a
diet- and host factor–dependent disease in which a dysbiotic oral microbiome generates an acidic environment,
leading to enamel demineralization. Our published work identified 10 salivary immunological markers that co-
occur with caries-associated bacterial species and are significantly elevated in children with caries compared
with caries-free children. Some of these markers are also elevated in children with ACEs. We propose the
existence of a brain–oral microbiome axis, supported by multiple reports describing the salivary induction of
NEI stress response markers that may alter the oral microbiome. We hypothesize that children with ACEs present
with oral microbiome dysbiosis, increased dental caries, and immune dysregulation, including alterations in
salivary stress or immunological molecules. This study aims to examine the associations among ACEs, the oral
microbiome, dental caries, and salivary stress and immunological biomarkers in children. The innovative study
design includes (1) strategies for enrolling a clinically meaningful, sex-balanced study population with an ACE
prevalence that resembles the national average; (2) a comprehensive investigation of salivary markers, the oral
microbiome, actual caries experiences, and covariate factors; and (3) a high-resolution metagenomics oral
microbiome investigation. Study findings will contribute to understanding ACE-associated dental caries by
identifying potential causative mechanisms at the oral microbiome level. The knowledge generated by this study
has the potential to directly impact the clinical management of children with ACEs, promoting medical–dental
integrated and trauma-informed approaches to ACE identification and caries prevention. Future policies may
benefit from considering the contrib...

## Key facts

- **NIH application ID:** 11057403
- **Project number:** 1R21DE033799-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Nini Chaichanasakul Tran
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $236,250
- **Award type:** 1
- **Project period:** 2024-09-16 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11057403

## Citation

> US National Institutes of Health, RePORTER application 11057403, The Role of Brain-Oral-Microbiome Axis in Adverse Childhood Experiences-associated Dental Caries in Children (1R21DE033799-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/11057403. Licensed CC0.

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