Proof of Concept: Gut Microbiota Dysbiosis May Influence Postoperative Delirium
Key findings
- This prospective observational cohort study investigated whether alterations in gut microbiota were associated with increased risk of postoperative delirium
- Among 86 patients who underwent orthopedic surgery, an increased postoperative abundance of the gut bacteria Parabacteroides distasonis was associated with a greater incidence of postoperative delirium (OR, 2.13; P=0.026)
- Although generally lower in delirious patients, decreases in the abundance of Prevotella and Collinsella were not significantly associated with delirium
- Compared with patients who did not develop postoperative delirium, the 10 patients who did had a higher abundance of postoperative gut Parabacteroides distasonis
- If confirmed, these findings suggest gut bacteria have the potential to be biomarkers of postoperative delirium and perhaps targets for intervention
It's been established recently that the gut–brain axis is essential in regulating brain function. Gut microbiota dysbiosis has been linked to cognitive impairment and Alzheimer's disease neuropathogenesis.
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In addition, researchers at Massachusetts General Hospital previously showed in geriatric mice that anesthesia/surgery reduced the abundance of gut lactobacillus and induced delirium-like behavior. Published in Aging, the study further demonstrated that treatment with lactobacillus or probiotics mitigated the behavior.
Now Yiying Zhang, MD, PhD, of the Mass General Department of Anesthesia, Critical Care and Pain Medicine, who serves as principal investigator for this project, and Zhongcong Xie, MD, PhD, director of the Geriatric Anesthesia Research Unit in the Department, and colleagues have conducted the first clinical study to show an association between gut microbiota and postoperative delirium in patients. They detail their findings in Translational Psychiatry.
Methods
The study participants were 86 patients, age 65 or older, who underwent elective total knee arthroplasty, total hip arthroplasty, or laminectomy under general or spinal anesthesia at Mass General between 2016 and 2020. Fecal swabs were collected immediately after surgery and analyzed with 16S ribosomal RNA gene sequencing, identifying the bacteria present down to the species level.
The researchers conducted a principal components analysis that identified eight disease-related bacteria most commonly present in the samples. They then selected three to analyze based on their relevance to inflammation, contributing to cognitive dysfunction: Parabacteroides distasonis, Prevotella, and Collinsella.
On postoperative day 1 and/or day 2, participants were interviewed with the Confusion Assessment Method (CAM) to determine the presence or absence of delirium. Regardless of CAM score, all participants were also assessed for delirium severity with the Memorial Delirium Assessment Scale.
Results
After adjustment for age and sex:
- The abundance of postoperative Parabacteroides distasonis (relative to the total number of bacterial sequences in each sample) was significantly associated with postoperative delirium (OR, 2.13; P=0.026)
- Prevotella and Collinsella were not significantly associated with the incidence of postoperative delirium
- None of the three bacteria was associated with the severity of postoperative delirium
The team then compared the relative abundances of the bacteria in the 10 participants who developed postoperative delirium and the 76 who did not:
- Parabacteroides distasonis—marginally higher in participants who developed delirium (P=0.064)
- Prevotella—marginally lower in participants who developed delirium (P=0.085)
- Collinsella—no significant difference between the two groups (P=0.212)
Conclusion
If it's confirmed gut microbiota dysbiosis plays a role in the development of postoperative delirium, gut bacteria have the potential to be biomarkers and even targets for intervention.
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