# Modulation of microbiome function by host-derived noncoding small RNA

> **NIH NIH R21** · UNIVERSITY OF FLORIDA · 2021 · $226,545

## Abstract

Summary:
A number of studies have reported changes in the composition of microbiota in diseases such as metabolic
syndrome, inflammatory bowel diseases, hypertension, Asthma, cardiovascular diseases, rheumatoid arthritis,
cancer and infection. Some of these links have been shown to be causative of diseases by using specific
bacteria introduced into pre-clinical models. For example, we showed that the human clinical isolate C. jejuni
(C. jejuni) 81-176 promote development of colitis-associated colorectal cancer through the production of
cytolethal distending toxin (cdt) (He Z et al. Gut. 2019; 68(2) 289-300). Importantly, mice colonized with C. jejuni
81-176 had a significantly different microbial gene expression profile compared to C. jejuni lacking the toxin cdtB
group, and different microbial communities as measured by 16S rDNA sequencing (He Z et al. Gut. 2019;
68(2):289-300). In addition, we demonstrated that the intestinal microbiota prevents C. jejuni-induced intestinal
inflammation in ex-GF Il10-/- mice, through bile acid metabolism (Sun X et al. Gastroenterology.
2018;154(6):1751-1763). Thus, disruption of microbial composition and function may be an important aspect of
disease mediated by enteropathogenic microorganisms. The mechanism implicated in maintaining a healthy
host-microbiota balance is complex and included production of host-derived anti-microbial peptides, mucus
barrier and immunoglobulin secretion among others. Recent findings from our laboratory suggest that human
intestinal microbiota obtained from healthy or colorectal tissues altered expression of mammalian-derived fecal
small RNAs such as miRNA, with some miRNAs preferentially targeting bacteria genes as predicted by
bioinformatic approach (Tomkovich S et al. mSystems. 2020; 5(1)). Many of these miRNAs were predicted to
target bacterial genes implicated in regulating motility, secretion, outer membrane proteins, stress response, iron
acquisition, and carbohydrate utilization/transport. Thus, host-derived production of small non-coding RNA may
represent another mean by which the host regulate microbiota function. This exciting concept is supported by
our preliminary data demonstrating gene knockdown in bacteria using mammalian extracellular vesicles (EVs)
loaded with siRNA targeting prokaryotic genes. These findings suggest that bacteria differentially impact host-
derived miRNA, which in turn could influence bacterial composition and gene expression. From these
observations, we hypothesize that bacteria influence the production of miRNA, which in turn modified microbiota
community function and consequently disease phenotype. We plan to test this hypothesis with the following two
specific aims:
Aim 1. Define the role of EV in bacteria-induced miRNA in Il10-/- mice.
Aim 2. Define the impact of EV-mediated siRNA on microbial gene expression.
This study will establish a proof of principal that enteric pathogens triggers selective EV-containing miRNA
differently affecting mi...

## Key facts

- **NIH application ID:** 10317154
- **Project number:** 1R21AI164741-01
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** Christian Jobin
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $226,545
- **Award type:** 1
- **Project period:** 2021-06-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10317154

## Citation

> US National Institutes of Health, RePORTER application 10317154, Modulation of microbiome function by host-derived noncoding small RNA (1R21AI164741-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10317154. Licensed CC0.

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