# Microbial, immune, metabolic perturbations by antibiotics (MIME study)

> **NIH NIH U01** · RBHS-ROBERT WOOD JOHNSON MEDICAL SCHOOL · 2021 · $340,550

## Abstract

More than 250 million courses of antibiotics are prescribed annually in the ambulatory care setting in the
United States alone, including more than 40 million in children under 18 years of age. The perception that
antibiotic use has minimal attendant adverse side effects contributes to the over-utilization of antibiotics in
clinical circumstances when they are not strictly indicated. Thus, among physicians and the public alike,
since the use of antibiotics seems to be relatively free of toxicity, there appears to be no disincentive to
their use despite marginal perceived or measured benefit. We have learned much about the human
microbiome – the large, highly diverse, bacterial community that lives in and on us. The emerging view is of
profound life-long bidirectional interactions between our microbiota and our cells; in essence, our
microbiota are a central part of human physiology. Perturbations in the microbiota affect metabolic,
immune, and cognitive physiology in experimental animal models. When a person takes an antibiotic, the
antibiotic diffuses via the blood into all body compartments, selecting for resistance. We propose to
examine the effects of two commonly used antibiotics [a tetracycline (doxycycline) and a beta-lactam
(amoxicillin)] on human microbial populations and on metabolic and immune physiology, studying healthy
human volunteers in a randomized clinical trial at the NIH Clinical Center (CC). Our hypothesis is that in
addition to acutely perturbing the human microbiome, these agents will have measurable metabolic and
immunologic effects, with residual effects in the weeks that follow.
To test this hypothesis, in Aim 1, we will assess the effects of a brief therapeutic course of antibiotics
on microbiota and metagenome composition. After an initial evaluation period, antibiotics will be given
for seven days, and there will be a prolonged post-treatment evaluation. Specimens will be obtained from
multiple sites at each of 10 time-points in total, and used for estimating bacterial and fungal composition
and gene content. In Aim 2, we will assess the effects of the antibiotic course on immune
physiology. At each time point, blood, urine, and feces will be obtained to determine plasma and cellular
levels of markers of both innate and adaptive immunity. In Aim 3, we will assess the effects of the
antibiotic course on metabolic physiology. The obtained blood and urine specimens will be assessed
for markers of metabolic and hormonal physiology. In a subset of subjects, we will utilize the unique CC
Metabolic Chamber to quantify 24-hour energy expenditure and its components (sleeping, diet-induced,
and activity) and carbohydrate and fat utilizations. In addition to the primary data analyses, we will build an
informatic model integrating the temporal data to provide insight into the complex intertwined physiology
between microbiome and host. This project is an opportunity to perform comprehensive and integrated
evaluations of pharmacolo...

## Key facts

- **NIH application ID:** 10159190
- **Project number:** 5U01AI122285-06
- **Recipient organization:** RBHS-ROBERT WOOD JOHNSON MEDICAL SCHOOL
- **Principal Investigator:** MARTIN J BLASER
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $340,550
- **Award type:** 5
- **Project period:** 2019-05-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10159190

## Citation

> US National Institutes of Health, RePORTER application 10159190, Microbial, immune, metabolic perturbations by antibiotics (MIME study) (5U01AI122285-06). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10159190. Licensed CC0.

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