Effect of Sevoflurane on the Intestinal Microbiome
The human intestinal microbiome is a complex and dynamic ecosystem that plays a central role in metabolism, immune regulation, and bioactive compound production.1 Its composition can vary dramatically according to specific genetic and environmental factors and can be disrupted by physiological stressors, such as surgery.2 Accumulating evidence demonstrates that both gastrointestinal and non-gastrointestinal surgeries significantly alter gut microbial diversity and composition, with changes observed in specific taxa that persist for weeks to months post-operation. Such alterations have been implicated in adverse outcomes, including postoperative infections and anastomotic complications. While factors such as antibiotic use, bowel preparation, nutrition, and surgical technique are known contributors to microbiome disruption, the independent role of anesthesia remains poorly understood.3 Clarifying the effects of different anesthetic agents such as sevoflurane on the intestinal microbiome is critical to improving patient outcomes.
In a 2021 experimental study, researchers investigated the effect of sevoflurane inhalational anesthesia on the intestinal microbiome by longitudinally assessing microbial changes in mice using rRNA gene sequencing. They also performed untargeted metabolomic analyses to characterize associated functional alterations. Sixteen 6–8-week-old male mice were randomly assigned to receive either 4 hours of sevoflurane anesthesia or no anesthesia, and fecal samples were collected for subsequent analysis.
Results showed sevoflurane anesthesia induced significant, time-dependent alterations in the intestinal microbiome. Principal component and principal coordinate analyses demonstrated clear differences between experimental and control groups on days 1, 3, and 7 after anesthesia, with the magnitude of contrast diminishing by day 14, a marker which suggests partial recovery. The most pronounced difference was on day 7, when the experimental group exhibited the lowest number of unique operational taxonomic units and a significant reduction in alpha diversity; this was followed by a slow trend toward restoration. Sustained compositional shifts were observed, including (semi-permanent) increases of Bacteroides, Alloprevotella, and Akkermansia bacteria and decreased Lactobacillus genera by day 14.
Further analyses revealed dynamic changes in microbial gene expression and metabolic pathways across various study time points. Differentially expressed genes were most abundant on days 3 and 14, while fewer were detected on days 1 and 7. Importantly, early alterations (day 1) were associated with pathways related to ribosomal function, nucleotide metabolism, and DNA repair. By day 7, pathways such as sphingolipid metabolism and the pentose phosphate pathway were enriched. By day 14, increased activity was observed in two-component systems, lipopolysaccharide biosynthesis, transcription machinery, and amino acid metabolism. Altogether, these findings indicate that sevoflurane anesthesia not only alters microbial composition but also induces sustained functional and metabolic reprogramming of the gut microbiome.3
Sevoflurane is believed to alter the intestinal microbiome through both direct and indirect mechanisms. Directly, in vitro studies show that sevoflurane exerts antibacterial effects against gram-positive, gram-negative, and even multidrug-resistant bacteria.4 Indirectly, it may influence microbial composition via the brain–gut–bacteria axis, a bidirectional communication network that links the central and enteric nervous systems with the gastrointestinal tract and its microbiota; this connection involves afferent (bottom-up) and efferent (top-down) signaling pathways.5
Research shows that sevoflurane anesthesia independently induces alterations in the intestinal microbiome’s composition, diversity, and metabolic function, with the most pronounced changes occurring one week after exposure. Although partial recovery was observed, persistent taxonomic and functional changes suggest anesthesia may have lasting effects on the intestinal ecosystem. These findings highlight the need to further investigate the clinical implications of anesthesia-related microbiome modulation, particularly given its potential relevance to postoperative outcomes and host systemic physiology.
References
1. Roux A, Payne SM, Gilmore MS. Microbial Telesensing: Probing the Environment for Friends, Foes, and Food. Cell Host & Microbe. 2009;6(2):115-124. https://doi.org/10.1016/j.chom.2009.07.004
2. Guyton K, Alverdy JC. The gut microbiota and gastrointestinal surgery. Nature Reviews Gastroenterology & Hepatology. 2016;14(1):43-54. https://doi.org/10.1038/nrgastro.2016.139
3. Han C, Zhang Z, Guo N, et al. Effects of Sevoflurane Inhalation Anesthesia on the Intestinal Microbiome in Mice. Frontiers in Cellular and Infection Microbiology. 2021;11. https://doi.org/10.3389/fcimb.2021.633527
4. Martínez-Serrano M, Gerónimo-Pardo M, Martínez-Monsalve A, Crespo-Sánchez MD. Antibacterial effect of sevoflurane and isoflurane. Revista espanola de quimioterapia : publicacion oficial de la Sociedad Espanola de Quimioterapia. 2017;30(2):84-89. https://pubmed.ncbi.nlm.nih.gov/28198170/
5. Gracie DJ, Hamlin PJ, Ford AC. The influence of the brain–gut axis in inflammatory bowel disease and possible implications for treatment. The Lancet Gastroenterology & Hepatology. 2019;4(8):632-642. https://doi.org/10.1016/S2468-1253(19)30089-5