Related Experiment Video
Updated: May 23, 2025
Operating and Biocontainment Procedures of a Facility for Laboratory Mice with a Natural Microbiome: Immunophenotyping Procedure
Published on: December 13, 2024
Effects of Perioperative Exposure on the Microbiome and Outcomes From an Immune Challenge in C57Bl/6 Adult Mice
Mara Serbanescu1, Seoho Lee2, Fengying Li2
1From the Division of Critical Care, Department of Anesthesiology, Duke University School of Medicine, Durham, North Carolina.
Background:
Previous work suggests that the gut microbiome can be disrupted by antibiotics, anesthetics, opiates, supplemental oxygen, or nutritional deprivation-all of which are common and potentially modifiable perioperative interventions that nearly all patients are exposed to in the setting of surgery. Gut microbial dysbiosis has been postulated to be a risk factor for poor surgical outcomes, but how perioperative care-independent of the surgical intervention-impacts the gut microbiome, and the potential consequences of this impact have not been directly investigated.
Methods:
We developed a perioperative exposure model (PEM) in C57Bl/6 mice to emulate the most common elements of perioperative medicine other than surgery, which included 12 hours of nutritional deprivation, 4 hours of volatile general anesthetic, 7 hours of supplemental oxygen, surgical antibiotics (cefazolin), and opioid pain medication (buprenorphine). Gut microbial dynamics and inferred metabolic changes were longitudinally assessed before-and at 3 time points after-PEM by 16S rRNA amplicon sequencing. We then used fecal microbial transplant in secondary abiotic mice to test if, compared to preexposure microbiota, day 3 post-PEM microbial communities affect the clinical response to immune challenge in an endotoxemia model.
Results:
We observed transient changes in microbiota structure and function after the PEM, including reduced biodiversity, loss of diverse commensals associated with health (including Lactobacillus , Roseburia , and Ruminococcus ), and changes in microbiota-mediated amino acid metabolic pathways. Mice engrafted with day 3 post-PEM microbial communities demonstrated markedly reduced survival after endotoxemia compared to those bearing preexposure communities (7-day survival of ~20% vs ~70%, P = .0002).
Conclusions:
These findings provide the first clear evidence that the combined effects of common perioperative factors, independent of surgery, cause gut microbial dysbiosis and alter the host response to inflammation in the postoperative period.
Insights
Common perioperative interventions, excluding surgery, disrupt the gut microbiome. This gut dysbiosis significantly reduces survival during endotoxemia, highlighting a critical link between perioperative care and patient outcomes.
Area of Science:
- Microbiology
- Immunology
- Gastroenterology
Background:
- Perioperative care involves interventions like antibiotics, anesthetics, and nutritional changes that can disrupt the gut microbiome.
- Gut microbial dysbiosis is a suspected risk factor for poor surgical outcomes.
- The impact of perioperative factors, separate from surgery itself, on the gut microbiome remains under-investigated.
Purpose of the Study:
- To investigate how common perioperative interventions, independent of surgical procedures, affect the gut microbiome.
- To determine the consequences of perioperative-induced gut dysbiosis on host immune response.
Main Methods:
- A perioperative exposure model (PEM) was established in mice, simulating nutritional deprivation, general anesthesia, supplemental oxygen, antibiotics, and opioid medication.
- Gut microbial composition and inferred metabolic functions were analyzed longitudinally using 16S rRNA sequencing.
- Fecal microbial transplants were used to assess the impact of post-PEM microbiota on host response to an endotoxemia challenge.
Main Results:
- The PEM induced transient gut microbial dysbiosis, characterized by reduced biodiversity and loss of beneficial commensals.
- Significant alterations in microbiota-mediated amino acid metabolism were observed.
- Mice receiving microbiota from day 3 post-PEM exhibited significantly lower survival rates (~20%) in an endotoxemia model compared to controls (~70%).
Conclusions:
- Common perioperative factors, independent of surgery, induce gut microbial dysbiosis.
- This perioperative-induced dysbiosis impairs the host's ability to respond to inflammatory challenges post-surgery.
- Findings underscore the critical role of perioperative care in shaping the gut microbiome and influencing postoperative outcomes.
More Related Videos
13:37A Mouse Tumor Model of Surgical Stress to Explore the Mechanisms of Postoperative Immunosuppression and Evaluate Novel Perioperative Immunotherapies
Published on: March 12, 2014
12:27The Utilization of Oropharyngeal Intratracheal PAMP Administration and Bronchoalveolar Lavage to Evaluate the Host Immune Response in Mice
Published on: April 2, 2014