# Microbiome Dysbiosis and Postoperative Delirium Pathogenesis

> **NIH NIH R21** · MASSACHUSETTS GENERAL HOSPITAL · 2020 · $459,136

## Abstract

Abstract
 Postoperative delirium (POD), a condition characterized by a state of confusion, is one of the most
common postoperative complications among senior patients and is associated with substantially increased
rates of morbidity and mortality, increased cost of care, and risk of developing Alzheimer’s disease and related
dementias (ADRD). However, even with ongoing POD studies, the pathogenesis of POD is still mostly
unknown, which impedes further studies of POD, including the targeted interventions. Thus, there is no
treatment for POD at present. Consistent with the notion that gut microbiota dysbiosis (e.g., gut microbiota
community structure changes), neuroinflammation and mitochondrial dysfunction are part of ADRD
neuropathogenesis and are also associated with cognitive impairments, our preliminary studies showed that
the open abdominal surgery under general anesthesia (anesthesia/surgery) induced an age-dependent gut
microbiota dysbiosis, neuroinflammation, mitochondrial dysfunction and POD-like behavior in the mice. Thus,
we will extend these studies to further define a potential multifactorial model of POD pathogenesis by testing
the following hypothesis: anesthesia/surgery-induced neuroinflammation (the precipitating factor and the
contributor) is promoted by age-associated microbiota dysbiosis (the predisposing factor and the modulator),
leading to mitochondrial dysfunction and POD-like behavior in mice. We will employ biochemical and
behavioral tools to accomplish two Specific Aims: (1) we will assess the effects of anesthesia/surgery on
gut microbiota and fecal b-amyloid, blood and brain level of IL-6, microglia activation, brain Ab and
mitochondrial function, and POD-like behavior in aged mice (18 month-old mice or 3 month-old germ-free mice
fed with feces of the 18 months old mice) as compared to those in adult mice (9 months old mice or 3 month-
old germ-free mice fed with feces of the 9 months old mice); (2) we will assess whether treatment with
butyrate, antibiotic (e.g., cefazolin) and probiotic can mitigate the POD-like behavior and their associated
changes in feces, blood, and brain in the mice. We will employ an innovative label-free nano-biosensing
system for biomolecular analysis (nanobeam technology) in the proposed studies. This proposal aims to
investigate an understudied topic in innovative systems through testing novel hypotheses. These studies could
ultimately help to develop the targeted interventions of POD by targeting microbiota dysbiosis. These efforts
would ultimately promote safer anesthesia and surgical care, leading to better postoperative outcomes for
senior patients and, consequently, the development of strategies towards preventing ADRD.

## Key facts

- **NIH application ID:** 10055132
- **Project number:** 1R21AG065606-01A1
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Shiqian Shen
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $459,136
- **Award type:** 1
- **Project period:** 2020-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10055132

## Citation

> US National Institutes of Health, RePORTER application 10055132, Microbiome Dysbiosis and Postoperative Delirium Pathogenesis (1R21AG065606-01A1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10055132. Licensed CC0.

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