# Circadian Regulation of Antibiotic Resistance in the Microbiome

> **NIH NIH F32** · UT SOUTHWESTERN MEDICAL CENTER · 2022 · $69,802

## Abstract

Project Summary
Humans must regulate a symbiotic relationship with almost 100 trillion intestinal bacteria which readily harbor
antibiotic resistance genes and the mechanisms that spread them. Despite the relentless rise of antibiotic
resistant infections little is known about the host factors that regulate antibiotic resistance development in vivo.
Preliminary investigations revealed that the mammalian circadian clock may be such a factor. Prior in vivo studies
have demonstrated that the circadian clock drives daily rhythms in microbiome composition which are
synchronized to the day-night cycle. However, gene expression in the microbiome at circadian time scales is
largely unexplored. To this end, a comprehensive study of the mouse microbiome was performed across the
day-night light cycle. These data revealed that beyond daily rhythms of microbe abundances, extensive
transcriptional rhythms occur in the microbiome across the day-night light cycle. Indeed, antibiotic resistance
and horizontal gene transfer systems showed some of the most significant transcriptional rhythms in the
microbiome, reaching peak expression within a 4-hour window each day. These preliminary data demonstrated
that transcription in the microbiome is temporally structured in vivo. These diurnal (daily) rhythms are
characteristic of regulation by the host’s circadian clock. Therefore, this proposal seeks to understand
mechanisms driving diurnal bacterial transcription in the microbiome by examining the in vivo regulation of
horizontal gene transfer and the impact of the host circadian clock on the spread of antibiotic resistance. Taken
together, this work proposes the circadian clock synchronizes transcription in the microbiome to the day-night
cycle, potentially revealing a mammalian regulator of antibiotic resistance development.

## Key facts

- **NIH application ID:** 10465012
- **Project number:** 1F32DK132913-01
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Alexander Crofts
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $69,802
- **Award type:** 1
- **Project period:** 2022-04-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10465012

## Citation

> US National Institutes of Health, RePORTER application 10465012, Circadian Regulation of Antibiotic Resistance in the Microbiome (1F32DK132913-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10465012. Licensed CC0.

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