# Microbiome and Nutrition in Severe PARDS

> **NIH NIH R01** · UNIVERSITY OF ARIZONA · 2021 · $509,973

## Abstract

PROJECT SUMMARY
Severe Pediatric Acute Respiratory Distress Syndrome (PARDS) is a life-threatening condition with high
mortality (33%). Novel therapies to improve mortality in this condition are critical. Multiple retrospective studies
from our group and others have demonstrated an association between early enteral nutrition (EEN) and
decreased mortality in children with PARDS, but mechanisms for this association are unclear. Crosstalk
between the lung and gut microbiome is a potential mechanism by which EEN may reduce PARDS mortality.
Diet can rapidly alter the relative abundance of beneficial butyrate-producing commensal gut bacteria to
increase fecal butyrate. In animal models of ARDS, butyrate pre-treatment decreases lung inflammation and
injury. We hypothesize, that in severe PARDS, EEN increases relative abundance of butyrate producing gut
commensals, thereby increasing butyrate levels and reducing acute lung inflammation and injury. EEN is a
novel pathway to improve outcomes in these children. The PROSpect study, a multi-center, NIH-funded
clinical trial, will randomize 1000 children with severe PARDS to compare positioning and ventilation strategies
to improve patient outcomes. This clinical trial presents a unique opportunity to investigate potential
mechanistic underpinnings of EEN as a targeted approach to improve outcomes for children with severe
PARDS. We will conduct our study as an ancillary study to the PROSpect study. The specific aims of our
study are: Aim 1:To test the hypothesis that relative abundance of butyrate producing fecal bacteria,
fecal butyrate, and patient outcomes differ by EEN exposure in severe PARDS. We will obtain fecal
specimens from 180 patients on days 0-7 of mechanical ventilation to assess the effect of EEN and type of
EEN ( ± prebiotics) on the gut microbiome signature with 16S rRNA gene sequencing. We will assess
differences in measured fecal butyrate and other short chain fatty acids (SCFA) by EEN and type of EEN. On a
subset of fecal samples, we will use whole genome shotgun metagenomics sequencing (WGS) to identify
species and strains of butyrate-producing commensal bacteria important in patients with PARDS. Aim 2: To
test the hypothesis that lower respiratory tract inflammation, acute lung injury, and innate immune cell
gene expression patterns differ by fecal SCFA concentration in severe PARDS. We will obtain
endotracheal aspirate specimens from patients in Aim 1 on PARDS days 0 and 3 to test associations between
fecal SCFA and critical cytokines implicated in PARDS lung pathophysiology, and key biomarkers of PARDS
acute lung injury. We will utilize whole tracheal aspirate single nuclei RNASeq (snRNASeq) to compare gene
expression patterns for tracheal aspirate immune cell populations in patients by fecal butyrate. This study will
improve our understanding of the mechanistic underpinnings for how EEN may improve clinical outcomes of
PARDS. Loss of butyrate producing commensal bacteria may prove to b...

## Key facts

- **NIH application ID:** 10178351
- **Project number:** 1R01HD104618-01
- **Recipient organization:** UNIVERSITY OF ARIZONA
- **Principal Investigator:** Katri Vanamo Typpo
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $509,973
- **Award type:** 1
- **Project period:** 2021-04-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10178351

## Citation

> US National Institutes of Health, RePORTER application 10178351, Microbiome and Nutrition in Severe PARDS (1R01HD104618-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10178351. Licensed CC0.

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