# The Role of Microbiome Modulation in Morphine-Induced Exacerbation of Pancreatitis

> **NIH NIH R01** · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · 2020 · $501,885

## Abstract

Project Abstract
Pancreatitis is an inflammatory disease of the pancreas causing significant morbidity, mortality and
hospitalization. Studies suggest that pancreatitis is also a risk factor for pancreatic cancer. There is no specific
therapy available for pancreatitis. One of the major symptoms for pancreatitis, whether acute or chronic is
severe pain and treatment strategies include pain management with narcotics. Despite their prevalent use as
analgesics in pancreatitis, the effect of opioids on the severity of the disease and its progression remain
unclear. Our published data suggest that therapeutic use of morphine in acute pancreatitis (AP) has profound
effect on disease progression and regenerative ability of the pancreas. Furthermore, our preliminary studies
suggest that therapeutic morphine treatment leads to increased severity of chronic pancreatitis (CP). These
results are highly significant as they suggest that morphine treatment of patients with AP may be making them
more susceptible to a severe course or likelihood of developing CP. Similarly, treatment of patients with
recurrent acute pancreatitis may make them more likely to evolve into CP. The mechanism by which morphine
impacts severity of pancreatitis is not known.
In addition to its immune-modulatory role, morphine has been implicated in causing dysbiosis. Modulation of
microbiome has been shown to drive inflammation in various inflammatory disease. While clinical studies have
demonstrated altered microbiome in patients with pancreatitis, the role of morphine induced modulation of gut
microbiome and its impact on severity of acute and chronic pancreatitis has not been studied till date. In the
current grant, we will evaluate the hypothesis that morphine worsens pancreatitis-induced local and systemic
injuries by inducing dysbiosis. In specific aim 1 we will elucidate the role of morphine-induced dysbiosis in
increasing severity of AP. In specific aim 2 we will elucidate the mechanism by which morphine-induced
dysbiosis leads to modulation of inflammation in AP. Specifically the role of neutrophilic and macrophage
dysfunction and the role of TLR-2 dependent processes will be evaluated. Finally, in specific aim 3, we will
evaluate the role and mechanism of opioid induced dysbiosis in worsening of CP. We will also compare
various opioids, with respect to their effect on severity of acute/chronic pancreatitis and we hope to translate
these findings into clinical trials for identification of the safer opioid. In light of the current opioid crisis and
increasing incidence of pancreatitis, these findings will pave the way for strategies that will counteract the
deleterious effects of opioid use in worsening pancreatitis outcomes. Modulation of gut microbiome with
probiotics may lead to alleviation of harmful effects of opioids in AP/CP.

## Key facts

- **NIH application ID:** 9882254
- **Project number:** 5R01DK117576-03
- **Recipient organization:** UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
- **Principal Investigator:** Sabita Roy
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $501,885
- **Award type:** 5
- **Project period:** 2018-06-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9882254

## Citation

> US National Institutes of Health, RePORTER application 9882254, The Role of Microbiome Modulation in Morphine-Induced Exacerbation of Pancreatitis (5R01DK117576-03). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/9882254. Licensed CC0.

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