Anesthesia and the Microbiome: New Frontiers in Perioperative Medicine

Hana Nadeem

Three leading experts presented their advances on the effect of anesthesia on the gut microbiota and how the outcome could be relevant in perioperative medicine in the AUA symposium, “Anesthesia and the Microbiome: Exploring A New Frontier in Perioperative Medicine” on May 15.

Cyrus Mintz, MD,PhD, from John Hopkins School of Medicine, started the symposium by presenting his research on the anesthetic effects on the gut microbiome. Do general anesthetics cause dysbiosis? Does it increase the risk of future infections and complications? Are there any treatment strategies available to prevent the long-term side effects of anesthetics? These three objectives were tackled in this project by using mice models and comparing a group control treated with 100% oxygen (O₂) to a group receiving 100% O₂ and isoflurane. Analyzing the stool and the genome of the exposed mice led to a decrease in the abundance and the diversity of the gut microbiome. At a molecular level, a reduction in adenosine level and its precursor metabolites was revealed postexposure to isoflurane as well as an increase in pyrimidine, carbohydrates and other metabolites. Although these metabolic pathways were altered, the biological meaning of these findings are still being developed.

“What are the consequences of isoflurane induced dysbiosis?” was the next question explored. Transplanting stool from isoflurane treated mice into knockout mice, followed by injection of an immune system stimulator (bacterial lipopolysaccharide), demonstrated an increased rate of mortality and sepsis in the transplanted mice. Even though the results were not statistically significant, there is still an indication of a biological significance at the level of the microbiome. Dr. Mintz ended his presentation by illustrating the use of the microbiome transplant as a model to study and explore more outcomes of anesthetics on the gut microbiota, and also to test prophylaxis strategies with probiotic to ultimately develop a probiotic design that could prevent these changes.

Shiqian Shen, MD, from Massachusetts General Hospital, followed Dr. Mintz with his discoveries on “Gut Microbiota’s Effect in Neuroinflammation and Pain.” Based on literature, moving from one place to another has a big effect on the composition of gut microbiota, and, therefore, the incidence of developing a neuroinflammatory condition. Spontaneous experimental autoimmune encephalomyelitis (EAE) incidence increased after colonization of germ-free mice with commensal microflora. Together with the myelin autoantigen, they cooperate to trigger an autoimmune demyelination and increased occurrence of neuropathic pain. Eliminating gut microbiota with wide spectrum antibiotics dampened the development of neuropathic pain as well as skewed T-cell immune response. In Dr. Shen’s study, a refractory response to neuroinflammation in a group of mice treated with antibiotics was observed after a chronic constrictive injury (CCI) to the sciatic nerve, concluding that eradication of gut microbiota prevents the development of neuropathic pain. Furthermore, microbiota influences neuropathic pain through modulating proinflammatory and anti-inflammatory T cells. Adding a noxious stimulus after eradicating gut microbiota inhibits T regulatory cells and stimulates the recruitment of proinflammatory Th1 cells. This effect proves that the eradication effect of gut microbiota on preventing the development of neuroinflammation is solely dependent on regulatory T cells.

Paul Wischmeyer, MD, EDIC, FASPEN, FCCM, from Duke University School of Medicine, wrapped up the panel with a presentation on “Gut Dysbiosis in Critical Illness and COVID-19.” He took a different approach, focusing on recent research clarifying the beneficial role of microbiome and its different outcomes on health conditions. Under stress, normal microbiome gets altered and diminishes in critical illness, causing a major loss of normal bacterial species and letting adhering and invading nosocomial pathogens like pseudomonas to become the dominant species in the gut. With time, skin, oral and fecal microbiome will begin to be identical, leading to loss of diversity and increased hospital length of stay. While studying the alteration in the microbiome, Dr. Wischmeyer noted a decreased level of fecal bacteria called “Faecalibacterium prausnitzii,” known by its anti-inflammatory effect in inflammatory bowel disease (IBD), along with an increase in certain species like Klebsiella and Enterobacteriaceae in skin microbiome, Mycoplasma in oral microbiome and Corococossus in fecal microbiome. The outcome of these changes was associated with a higher incidence of bacteremia, ARDS and IBD.

Due to this fact, Dr. Wischmeyer highlighted the use of probiotic. Based on systematic review stated during the presentation, probiotics were able to reduce antibiotic-associated diarrhea, reduce the rate of ventilator-associated pneumonia and upper respiratory tract infection. Keeping this outcome in mind, Dr. Wischmeyer mentioned his ongoing clinical trial, based on using probiotics to eliminate COVID-19 transmission in exposed household contacts. It entails modifying the microbiome with probiotic that has potential to reduce symptomatic COVID-19 rate. He recommended at the end of the panel to prescribe patients bacteria instead of eradicating them in order to restore balance, increase diversity of gut microbiome and decrease rate of health conditions and infections.