Differential Regulation of Postoperative Gut Microbiota by Inhalation vs Intravenous Anesthesia: NF-κB/HIF-1α-Mediated Macrophage Polarization.
- 1Department of Anesthesiology, The Affiliated People's Hospital of Ningbo University, Ningbo, Zhejiang, China.
Abstract
Background
Perioperative anesthetic strategies are increasingly recognized as important modulators of postoperative immune responses and intestinal microecological homeostasis following gastrointestinal surgery.Objective
To systematically explore the differential effects of inhalational anesthesia (sevoflurane) and intravenous anesthesia (propofol) on postoperative intestinal microbiota, and to investigate the potential association between anesthetic methods, NF-κB/HIF-1α signaling pathway, and macrophage polarization using integrated bioinformatics analyses.Methods
Publicly available datasets were retrieved from NCBI SRA, GEO, and EMBL-EBI to identify three independent cohorts with clear annotations of gastrointestinal surgery and anesthetic methods. A total of 90 samples were included (30 control, 30 inhalational anesthesia, and 30 intravenous anesthesia). Intestinal microbiota profiles derived from 16S rRNA sequencing were integrated with expression data of NF-κB/HIF-1α pathway-related genes. Microbial diversity, community composition, differential taxa, functional enrichment, and microbe-gene correlations were analyzed using QIIME2, limma, vegan, and related bioinformatics tools to construct the regulatory axis of "anesthetic method-intestinal microbiota-signaling pathway-macrophage polarization."Results
The inhalational anesthesia group exhibited significantly reduced α-diversity (Chao1 and Shannon indices) compared with both the control and intravenous anesthesia groups (P<0.05). β-diversity analysis revealed distinct microbial community structures among the three groups (PERMANOVA R²=0.27, P=0.001). Genus-level analysis demonstrated a marked enrichment of Bacteroides in the inhalational anesthesia group, whereas Lactobacillus and Bifidobacterium were predominant in the control group. LEfSe analysis identified eight significantly differential genera. Expression of pro-inflammatory NF-κB/HIF-1α pathway genes (NFKB1, IL-6, TNF-α) was significantly up-regulated in the inhalational anesthesia group, accompanied by down-regulation of anti-inflammatory markers (ARG1, IL-10). These alterations were less pronounced in the intravenous anesthesia group. Correlation analysis identified Bacteroides-NFKB1 and Lactobacillus-IL-10 as key regulatory nodes. Functional enrichment revealed inflammation-related pathways enriched under inhalational anesthesia, whereas short-chain fatty acid synthesis pathways were enriched in controls.Conclusion
Inhalational anesthesia is associated with greater disruption of postoperative intestinal microbiota homeostasis than intravenous anesthesia, and is correlated with NF-κB/HIF-1α-related pro-inflammatory macrophage polarization. These findings provide bioinformatics evidence supporting propofol-based intravenous anesthesia and microbiota-targeted strategies to improve postoperative outcomes.
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BibTeX
@article{chen2026differential,
title = {{Differential Regulation of Postoperative Gut Microbiota by Inhalation vs Intravenous Anesthesia: NF-κB/HIF-1α-Mediated Macrophage Polarization.}},
author = {Nami Chen and Cixian Hu and Xin Huang and Liming Zhao},
journal = {Iranian journal of biotechnology},
year = {2026},
month = oct,
doi = {10.30498/ijb.2026.572902.4361},
url = {https://europepmc.org/article/MED/42928741},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Differential Regulation of Postoperative Gut Microbiota by Inhalation vs Intravenous Anesthesia: NF-κB/HIF-1α-Mediated Macrophage Polarization.
AU - Nami Chen
AU - Cixian Hu
AU - Xin Huang
AU - Liming Zhao
PY - 2026
DA - 2026/10/01
JO - Iranian journal of biotechnology
DO - 10.30498/ijb.2026.572902.4361
UR - https://europepmc.org/article/MED/42928741
AB - Background Perioperative anesthetic strategies are increasingly recognized as important modulators of postoperative immune responses and intestinal microecological homeostasis following gastrointestinal surgery.Objective To systematically explore the differential effects of inhalational anesthesia (sevoflurane) and intravenous anesthesia (propofol) on postoperative intestinal microbiota, and to investigate the potential association between anesthetic methods, NF-κB/HIF-1α signaling pathway, and macrophage polarization using integrated bioinformatics analyses.Methods Publicly available datasets were retrieved from NCBI SRA, GEO, and EMBL-EBI to identify three independent cohorts with clear annotations of gastrointestinal surgery and anesthetic methods. A total of 90 samples were included (30 control, 30 inhalational anesthesia, and 30 intravenous anesthesia). Intestinal microbiota profiles derived from 16S rRNA sequencing were integrated with expression data of NF-κB/HIF-1α pathway-related genes. Microbial diversity, community composition, differential taxa, functional enrichment, and microbe-gene correlations were analyzed using QIIME2, limma, vegan, and related bioinformatics tools to construct the regulatory axis of "anesthetic method-intestinal microbiota-signaling pathway-macrophage polarization."Results The inhalational anesthesia group exhibited significantly reduced α-diversity (Chao1 and Shannon indices) compared with both the control and intravenous anesthesia groups (P<0.05). β-diversity analysis revealed distinct microbial community structures among the three groups (PERMANOVA R²=0.27, P=0.001). Genus-level analysis demonstrated a marked enrichment of Bacteroides in the inhalational anesthesia group, whereas Lactobacillus and Bifidobacterium were predominant in the control group. LEfSe analysis identified eight significantly differential genera. Expression of pro-inflammatory NF-κB/HIF-1α pathway genes (NFKB1, IL-6, TNF-α) was significantly up-regulated in the inhalational anesthesia group, accompanied by down-regulation of anti-inflammatory markers (ARG1, IL-10). These alterations were less pronounced in the intravenous anesthesia group. Correlation analysis identified Bacteroides-NFKB1 and Lactobacillus-IL-10 as key regulatory nodes. Functional enrichment revealed inflammation-related pathways enriched under inhalational anesthesia, whereas short-chain fatty acid synthesis pathways were enriched in controls.Conclusion Inhalational anesthesia is associated with greater disruption of postoperative intestinal microbiota homeostasis than intravenous anesthesia, and is correlated with NF-κB/HIF-1α-related pro-inflammatory macrophage polarization. These findings provide bioinformatics evidence supporting propofol-based intravenous anesthesia and microbiota-targeted strategies to improve postoperative outcomes.
SN - 1728-3043
SN - 2322-2921
ER -