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. 2023 Apr 27;17:1156453. doi: 10.3389/fnins.2023.1156453

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Copyright © 2023 Zhang, Wu, Liu, Huang, Zhou and Liang.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Surgery/anesthesia stress-induced and perioperative cefazolin-induced gut dysbacteria, inflammation, and cognitive dysfunction, respectively. (A,B) Surgery/anesthesia stress decreased context-related (q = 9.737, p < 0.0001) and cue tone-related (q = 6.635, p = 0.0002) freezing behavior at 1 week, while cefazolin could improve context-related (q = 4.996, p = 0.0041) and cue tone-related (q = 8.229, p < 0.0001) freezing behavior (n = 10, ANOVA with Tukey’s multiple comparisons test). (C,D) At 3 weeks after surgery, surgery/anesthesia stress-induced freezing behavior recovered, while cefazolin decreased context-related (vs. control, q = 6.671, p = 0.0002; vs. surgery, q = 5.078, p = 0.0036) and cue tone-related (vs. control, q = 7.029, p < 0.0001; vs. surgery, q = 5.193, p = 0.0029) freezing behavior (n = 10, ANOVA with Tukey’s multiple comparisons test). (E,F) ELISA: surgery/anesthesia stress increased the level of IL-1β in the hippocampus (q = 13.66, p < 0.0001) and colon (q = 6.832, p = 0.0004) at 1 week, respectively; at 3 weeks, only IL-1β in the colon (q = 4.177, p = 0.0171) was elevated by surgery/anesthesia stress; cefazolin could alleviate increasing IL-1β in the hippocampus (q = 8.005, p < 0.0001) at 1 week, but at 3 weeks, could enhance IL-1β in the hippocampus (q = 6.925, p = 0.0001) and colon (q = 6.437, p = 0.0003), respectively (n = 10, ANOVA with Tukey’s multiple comparisons test). (G,H) ELISA: surgery/anesthesia stress increased the level of IL-18 in the hippocampus (q = 7.902, p < 0.0001) and colon (q = 6.803, p = 0.0004) at 1 week, respectively; at 3 weeks, cefazolin could enhance IL-18 in the hippocampus (q = 8.352, p < 0.0001) and colon (q = 4.697, p = 0.0101), respectively (n = 10, ANOVA with Tukey’s multiple comparisons test). (I,J) Surgery/anesthesia stress increased the relative abundance of gram-positive bacteria (q = 0.0638, p = 0.0142) and decreased the relative abundance of gram-negative bacteria (q = 0.0638, p = 0.0142) of intestinal microbiota at 1 week. In contrast, cefazolin increased the relative abundance of gram-positive bacteria (q = 0.0733, p = 0.0244). It decreased the relative abundance of gram-negative bacteria (q = 0.0733, p = 0.0244) of intestinal microbiota at 3 weeks after surgery (n = 9, KW rank sum test with Wilcoxon rank sum test). G⁺: gram-positive bacteria; G⁻: gram-negative bacteria. ^*Compared with control, p < 0.05; ^#compared with surgery, p < 0.05; ^{^}compared with 3 weeks, p < 0.05.