Advances in the study of gut microbiota and postoperative pain：mechanisms and prospects for clinical application_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

LIU Xusheng ¹ , LIU Jianxiao ¹ , PENG Bo ¹ ,  YU Yongjiang ^1,2

1. The First Clinical Medical College of Lanzhou University, Lanzhou 730000, P. R. China;
2. Department of Gastrointestinal Surgery, Hernia and Abdominal Wall Surgery, The First Hospital of Lanzhou University, Lanzhou 730000, P. R. China;

Corresponding author：

YU Yongjiang, Email: ylongy@163.com

Keywords：

gut microbiota; postoperative pain; review

DOI：

10.7507/1007-9424.202408032

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective To summarise the influencing factors of gut microbiota in the perioperative period and its regulatory mechanism in postoperative pain, with the aim of providing clinical reference for postoperative pain management. Method Relevant literatures on gut microbiota and postoperative pain in recent years were systematically reviewed and synthesised. Results Anaesthesia, preoperative mechanical bowel preparation, surgical stress, etc. could cause gut microbiota dysbiosis. Gut microbiota directly or indirectly modulated the excitability of primary sensory neurons through their derived metabolites and pathogen-associated molecular patterns and influenced the pain signalling process by activating immune cells to release cytokines. Conclusions Gut microbiota play an important role in the development and progression of postoperative pain. Future studies should further clarify its role in different types of postoperative pain and develop innovative therapeutic strategies based on the regulation of gut microbiota to improve the management of postoperative pain.

1.	Boezaart AP, Smith CR, Chembrovich S, et al. Visceral versus somatic pain: an educational review of anatomy and clinical implications. Reg Anesth Pain Med, 2021, 46(7): 629-636.
2.	Akire SC, Bayraktar N. Outcomes of pain management among postoperative patients: A cross-sectional study. J Perianesth Nurs, 2024, 39(2): 240-245.
3.	Pan C, Zhang H, Zhang L, et al. Surgery-induced gut microbial dysbiosis promotes cognitive impairment via regulation of intestinal function and the metabolite palmitic amide. Microbiome, 2023, 11(1): 248. doi: 10.1186/s40168-023-01689-6.
4.	Masaud K, Collins JM, Rubio RC, et al. The gut microbiota in persistent post-operative pain following breast cancer surgery. Sci Rep, 2024, 14(1): 12401. doi: 10.1038/s41598-024-62397-1.
5.	Ghaderi F, Sotoodehnejadnematalahi F, Hajebrahimi Z, et al. Effects of active, inactive, and derivatives of Akkermansia muciniphila on the expression of the endocannabinoid system and PPARs genes. Sci Rep, 2022, 12(1): 10031. doi: 10.1038/s41598-022-13840-8.
6.	Brenner D, Cherry P, Switzer T, et al. Pain after upper limb surgery under peripheral nerve block is associated with gut microbiome composition and diversity. Neurobiol Pain, 2021, 10: 100072. doi: 10.1016/j.ynpai.2021.100072.
7.	Yang Y, Xu Z, Guo J, et al. Exploring the gut microbiome-postoperative cognitive dysfunction connection: Mechanisms, clinical implications, and future directions. Brain Behav Immun Health, 2024, 38: 100763. doi: 10.1016/j.bbih.2024.100763.
8.	Agnes A, Puccioni C, D'Ugo D, et al. The gut microbiota and colorectal surgery outcomes: facts or hype? A narrative review. BMC Surg, 2021, 21(1): 83. doi: 10.1186/s12893-021-01087-5.
9.	Mayer EA, Nance K, Chen S. The gut-brain axis. Annu Rev Med, 2022, 73: 439-453.
10.	Li D, Li Y, Yang S, et al. Diet-gut microbiota-epigenetics in metabolic diseases: From mechanisms to therapeutics. Biomed Pharmacother, 2022, 153: 113290. doi: 10.1016/j.biopha.2022.113290.
11.	Alen NV. The cholinergic anti-inflammatory pathway in humans: State-of-the-art review and future directions. Neurosci Biobehav Rev, 2022, 136: 104622. doi: 10.1016/j.neubiorev.2022.104622.
12.	Liufu N, Liu L, Shen S, et al. Anesthesia and surgery induce age-dependent changes in behaviors and microbiota. Aging (Albany NY), 2020, 12(2): 1965-1986.
13.	Han C, Zhang Z, Guo N, et al. Effects of sevoflurane inhalation anesthesia on the intestinal microbiome in mice. Front Cell Infect Microbiol, 2021, 11: 633527. doi: 10.3389/fcimb.2021.633527.
14.	Guo N, Zhang Z, Han C, et al. Effects of continuous intravenous infusion of propofol on intestinal flora in rats. Biomed Pharmacother, 2021, 134: 111080. doi: 10.1016/j.biopha.2020.111080.
15.	Wang H, Luo J, Chen X, et al. Clinical observation of the effects of oral opioid on inflammatory cytokines and gut microbiota in patients with moderate to severe cancer pain: A retrospective cohort study. Pain Ther, 2022, 11(2): 667-681.
16.	Li M, Qian W, Yu L, et al. Multi-time-point fecal sampling in human and mouse reveals the formation of new homeostasis in gut microbiota after bowel cleansing. Microorganisms, 2022, 10(12): 2317. doi: 10.3390/microorganisms10122317.
17.	Zheng Z, Hu Y, Tang J, et al. The implication of gut microbiota in recovery from gastrointestinal surgery. Front Cell Infect Microbiol, 2023, 13: 1110787. doi: 10.3389/fcimb.2023.1110787.
18.	Jalanka J, Salonen A, Salojärvi J, et al. Effects of bowel cleansing on the intestinal microbiota. Gut, 2015, 64(10): 1562-1568.
19.	Nalluri-Butz H, Bobel MC, Nugent J, et al. A pilot study demonstrating the impact of surgical bowel preparation on intestinal microbiota composition following colon and rectal surgery. Sci Rep, 2022, 12(1): 10559. doi: 10.1038/s41598-022-14819-1.
20.	祝林青, 吴晓雅, 张佳琳, 等. 肠道菌群在减重代谢手术后的变化及对术后并发症影响的研究进展. 中国普外基础与临床杂志, 2023, 30(11): 1378-83.
21.	Shogan BD, Smith DP, Christley S, et al. Intestinal anastomotic injury alters spatially defined microbiome composition and function. Microbiome, 2014, 2: 35. doi: 10.1186/2049-2618-2-35.
22.	Fyntanidou B, Amaniti A, Soulioti E, et al. Probiotics in postoperative pain management. J Pers Med, 2023, 13(12): 1645. doi: 10.3390/jpm13121645.
23.	Chen J, Wang Y, Shi Y, et al. Association of gut microbiota with intestinal ischemia/reperfusion injury. Front Cell Infect Microbiol, 2022, 12: 962782. doi: 10.3389/fcimb.2022.962782.
24.	Wilmes L, Collins JM, O'Riordan KJ, et al. Of bowels, brain and behavior: A role for the gut microbiota in psychiatric comorbidities in irritable bowel syndrome. Neurogastroenterol Motil, 2021, 33(3): e14095. doi: 10.1111/nmo.14095.
25.	Lee GI, Neumeister MW. Pain: pathways and physiology. Clin Plast Surg, 2020, 47(2): 173-180.
26.	Vergne-Salle P, Bertin P. Chronic pain and neuroinflammation. Joint Bone Spine, 2021, 88(6): 105222. doi: 10.1016/j.jbspin.2021.105222.
27.	Chen G, Zhang YQ, Qadri YJ, et al. Microglia in pain: detrimental and protective roles in pathogenesis and resolution of pain. Neuron, 2018, 100(6): 1292-1311.
28.	Abdel-Haq R, Schlachetzki JCM, Glass CK, et al. Microbiome-microglia connections via the gut-brain axis. J Exp Med, 2019, 216(1): 41-59.
29.	Ji RR, Chamessian A, Zhang YQ. Pain regulation by non-neuronal cells and inflammation. Science, 2016, 354(6312): 572-577.
30.	Chiu IM. Infection, pain, and itch. Neurosci Bull, 2018, 34(1): 109-119.
31.	Perez-Burgos A, Wang L, McVey Neufeld KA, et al. The TRPV1 channel in rodents is a major target for antinociceptive effect of the probiotic Lactobacillus reuteri DSM 17938. J Physiol, 2015, 593(17): 3943-3957.
32.	Miller RE, Ishihara S, Tran PB, et al. An aggrecan fragment drives osteoarthritis pain through Toll-like receptor 2. JCI Insight, 2018, 3(6): e95704. doi: 10.1172/jci.insight.95704.
33.	Liu T, Gao YJ, Ji RR. Emerging role of Toll-like receptors in the control of pain and itch. Neurosci Bull, 2012, 28(2): 131-144.
34.	Diogenes A, Ferraz CC, Akopian AN, et al. LPS sensitizes TRPV1 via activation of TLR4 in trigeminal sensory neurons. J Dent Res, 2011, 90(6): 759-764.
35.	Maruyama K, Takayama Y, Sugisawa E, et al. The ATP transporter VNUT mediates induction of dectin-1-triggered candida nociception. iScience, 2018, 6: 306-318.
36.	Tang Y, Du J, Wu H, et al. Potential therapeutic effects of short-chain fatty acids on chronic pain. Curr Neuropharmacol, 2024, 22(2): 191-203.
37.	Kukkar A, Singh N, Jaggi AS. Attenuation of neuropathic pain by sodium butyrate in an experimental model of chronic constriction injury in rats. J Formos Med Assoc, 2014, 113(12): 921-928.
38.	Su X, Gao Y, Yang R. Gut microbiota derived bile acid metabolites maintain the homeostasis of gut and systemic immunity. Front Immunol, 2023, 14: 1127743. doi: 10.3389/fimmu.2023.1127743.
39.	Lieu T, Jayaweera G, Zhao P, et al. The bile acid receptor TGR5 activates the TRPA1 channel to induce itch in mice. Gastroenterology, 2014, 147(6): 1417-1428.
40.	Nagy-Grócz G, Spekker E, Vécsei L. Kynurenines, neuronal excitotoxicity, and mitochondrial oxidative stress: role of the intestinal flora. Int J Mol Sci, 2024, 25(3): 1698. doi: 10.3390/ijms25031698.
41.	Resta F, Masi A, Sili M, et al. Kynurenic acid and zaprinast induce analgesia by modulating HCN channels through GPR35 activation. Neuropharmacology, 2016, 108: 136-143.
42.	Pokusaeva K, Johnson C, Luk B, et al. GABA-producing Bifidobacterium dentium modulates visceral sensitivity in the intestine. Neurogastroenterol Motil, 2017, 29(1): e12904. doi: 10.1111/nmo.12904.
43.	Abd-Elsayed A, Vardhan S, Aggarwal A, et al. Mechanisms of action of dorsal root ganglion stimulation. Int J Mol Sci, 2024, 25(7): 3591. doi: 10.3390/ijms25073591.
44.	Haq S, Grondin JA, Khan WI. Tryptophan-derived serotonin-kynurenine balance in immune activation and intestinal inflammation. FASEB J, 2021, 35(10): e21888. doi: 10.1096/fj.202100702R.
45.	Menni A, Moysidis M, Tzikos G, et al. Looking for the ideal probiotic healing regime. Nutrients, 2023, 15(13): 3055. doi: 10.3390/nu15133055.
46.	York AG, Skadow MH, Oh J, et al. IL-10 constrains sphingolipid metabolism to limit inflammation. Nature, 2024, 627(8004): 628-635.
47.	Khan J, Puchimada B, Kadouri D, et al. The anti-nociceptive effects of Porphyromonas gingivalis lipopolysaccharide. Arch Oral Biol, 2019, 102: 193-198.
48.	Dubey AK, Podia M, Priyanka None, et al. Insight into the beneficial role of lactiplantibacillus plantarum supernatant against bacterial infections, oxidative stress, and wound healing in A549 cells and BALB/c mice. Front Pharmacol, 2021, 12: 728614. doi: 10.3389/fphar.2021.728614.
49.	Panagiotou D, Filidou E, Gaitanidou M, et al. Role of Lactiplantibacillus plantarum UBLP-40, Lactobacillus rhamnosus UBLR-58 and Bifidobacterium longum UBBL-64 in the wound healing process of the excisional skin. Nutrients, 2023, 15(8): 1822. doi: 10.3390/nu15081822.
50.	Tarapatzi G, Filidou E, Kandilogiannakis L, et al. The Probiotic Strains Bifidοbacterium lactis, Lactobacillus acidophilus, Lactiplantibacillus plantarum and Saccharomyces boulardii Regulate Wound Healing and Chemokine Responses in Human Intestinal Subepithelial Myofibroblasts. Pharmaceuticals (Basel), 2022, 15(10): 1293. doi: 10.3390/ph15101293.
51.	Yoshimura A, Aki D, Ito M. SOCS, SPRED, and NR4a: Negative regulators of cytokine signaling and transcription in immune tolerance. Proc Jpn Acad Ser B Phys Biol Sci, 2021, 97(6): 277-291.
52.	Vale GC, Mota BIS, Ando-Suguimoto ES, et al. Effect of Probiotics Lactobacillus acidophilus and Lacticaseibacillus rhamnosus on Antibacterial Response Gene Transcription of Human Peripheral Monocytes. Probiotics Antimicrob Proteins, 2023, 15(2): 264-274.
53.	Altaib H, Nakamura K, Abe M, et al. Differences in the concentration of the fecal neurotransmitters GABA and glutamate are associated with microbial composition among healthy human subjects. Microorganisms, 2021, 9(2): 378. doi: 10.3390/microorganisms9020378.
54.	Ferrés-Amat E, Espadaler-Mazo J, Calvo-Guirado JL, et al. Probiotics diminish the post-operatory pain following mandibular third molar extraction: a randomised double-blind controlled trial (pilot study). Benef Microbes, 2020, 11(7): 631-639.
55.	Fuller AM, Bharde S, Sikandar S. The mechanisms and management of persistent postsurgical pain. Front Pain Res (Lausanne), 2023, 4: 1154597. doi: 10.3389/fpain.2023.1154597.
56.	McVey Neufeld KA, Strain CR, Pusceddu MM, et al. Lactobacillus rhamnosus GG soluble mediators ameliorate early life stress-induced visceral hypersensitivity and changes in spinal cord gene expression. Neuronal Signal, 2020, 4(4): NS20200007. doi: 10.1042/NS20200007.
57.	Liu YW, Wang YP, Yen HF, et al. Lactobacillus plantarum PS128 Ameliorated visceral hypersensitivity in rats through the gut-brain axis. Probiotics Antimicrob Proteins, 2020, 12(3): 980-993.
58.	Ringel-Kulka T, Goldsmith JR, Carroll IM, et al. Lactobacillus acidophilus NCFM affects colonic mucosal opioid receptor expression in patients with functional abdominal pain—a randomised clinical study. Aliment Pharmacol Ther, 2014, 40(2): 200-207.

1. Boezaart AP, Smith CR, Chembrovich S, et al. Visceral versus somatic pain: an educational review of anatomy and clinical implications. Reg Anesth Pain Med, 2021, 46(7): 629-636.
2. Akire SC, Bayraktar N. Outcomes of pain management among postoperative patients: A cross-sectional study. J Perianesth Nurs, 2024, 39(2): 240-245.
3. Pan C, Zhang H, Zhang L, et al. Surgery-induced gut microbial dysbiosis promotes cognitive impairment via regulation of intestinal function and the metabolite palmitic amide. Microbiome, 2023, 11(1): 248. doi: 10.1186/s40168-023-01689-6.
4. Masaud K, Collins JM, Rubio RC, et al. The gut microbiota in persistent post-operative pain following breast cancer surgery. Sci Rep, 2024, 14(1): 12401. doi: 10.1038/s41598-024-62397-1.
5. Ghaderi F, Sotoodehnejadnematalahi F, Hajebrahimi Z, et al. Effects of active, inactive, and derivatives of Akkermansia muciniphila on the expression of the endocannabinoid system and PPARs genes. Sci Rep, 2022, 12(1): 10031. doi: 10.1038/s41598-022-13840-8.
6. Brenner D, Cherry P, Switzer T, et al. Pain after upper limb surgery under peripheral nerve block is associated with gut microbiome composition and diversity. Neurobiol Pain, 2021, 10: 100072. doi: 10.1016/j.ynpai.2021.100072.
7. Yang Y, Xu Z, Guo J, et al. Exploring the gut microbiome-postoperative cognitive dysfunction connection: Mechanisms, clinical implications, and future directions. Brain Behav Immun Health, 2024, 38: 100763. doi: 10.1016/j.bbih.2024.100763.
8. Agnes A, Puccioni C, D'Ugo D, et al. The gut microbiota and colorectal surgery outcomes: facts or hype? A narrative review. BMC Surg, 2021, 21(1): 83. doi: 10.1186/s12893-021-01087-5.
9. Mayer EA, Nance K, Chen S. The gut-brain axis. Annu Rev Med, 2022, 73: 439-453.
10. Li D, Li Y, Yang S, et al. Diet-gut microbiota-epigenetics in metabolic diseases: From mechanisms to therapeutics. Biomed Pharmacother, 2022, 153: 113290. doi: 10.1016/j.biopha.2022.113290.
11. Alen NV. The cholinergic anti-inflammatory pathway in humans: State-of-the-art review and future directions. Neurosci Biobehav Rev, 2022, 136: 104622. doi: 10.1016/j.neubiorev.2022.104622.
12. Liufu N, Liu L, Shen S, et al. Anesthesia and surgery induce age-dependent changes in behaviors and microbiota. Aging (Albany NY), 2020, 12(2): 1965-1986.
13. Han C, Zhang Z, Guo N, et al. Effects of sevoflurane inhalation anesthesia on the intestinal microbiome in mice. Front Cell Infect Microbiol, 2021, 11: 633527. doi: 10.3389/fcimb.2021.633527.
14. Guo N, Zhang Z, Han C, et al. Effects of continuous intravenous infusion of propofol on intestinal flora in rats. Biomed Pharmacother, 2021, 134: 111080. doi: 10.1016/j.biopha.2020.111080.
15. Wang H, Luo J, Chen X, et al. Clinical observation of the effects of oral opioid on inflammatory cytokines and gut microbiota in patients with moderate to severe cancer pain: A retrospective cohort study. Pain Ther, 2022, 11(2): 667-681.
16. Li M, Qian W, Yu L, et al. Multi-time-point fecal sampling in human and mouse reveals the formation of new homeostasis in gut microbiota after bowel cleansing. Microorganisms, 2022, 10(12): 2317. doi: 10.3390/microorganisms10122317.
17. Zheng Z, Hu Y, Tang J, et al. The implication of gut microbiota in recovery from gastrointestinal surgery. Front Cell Infect Microbiol, 2023, 13: 1110787. doi: 10.3389/fcimb.2023.1110787.
18. Jalanka J, Salonen A, Salojärvi J, et al. Effects of bowel cleansing on the intestinal microbiota. Gut, 2015, 64(10): 1562-1568.
19. Nalluri-Butz H, Bobel MC, Nugent J, et al. A pilot study demonstrating the impact of surgical bowel preparation on intestinal microbiota composition following colon and rectal surgery. Sci Rep, 2022, 12(1): 10559. doi: 10.1038/s41598-022-14819-1.
20. 祝林青, 吴晓雅, 张佳琳, 等. 肠道菌群在减重代谢手术后的变化及对术后并发症影响的研究进展. 中国普外基础与临床杂志, 2023, 30(11): 1378-83.
21. Shogan BD, Smith DP, Christley S, et al. Intestinal anastomotic injury alters spatially defined microbiome composition and function. Microbiome, 2014, 2: 35. doi: 10.1186/2049-2618-2-35.
22. Fyntanidou B, Amaniti A, Soulioti E, et al. Probiotics in postoperative pain management. J Pers Med, 2023, 13(12): 1645. doi: 10.3390/jpm13121645.
23. Chen J, Wang Y, Shi Y, et al. Association of gut microbiota with intestinal ischemia/reperfusion injury. Front Cell Infect Microbiol, 2022, 12: 962782. doi: 10.3389/fcimb.2022.962782.
24. Wilmes L, Collins JM, O'Riordan KJ, et al. Of bowels, brain and behavior: A role for the gut microbiota in psychiatric comorbidities in irritable bowel syndrome. Neurogastroenterol Motil, 2021, 33(3): e14095. doi: 10.1111/nmo.14095.
25. Lee GI, Neumeister MW. Pain: pathways and physiology. Clin Plast Surg, 2020, 47(2): 173-180.
26. Vergne-Salle P, Bertin P. Chronic pain and neuroinflammation. Joint Bone Spine, 2021, 88(6): 105222. doi: 10.1016/j.jbspin.2021.105222.
27. Chen G, Zhang YQ, Qadri YJ, et al. Microglia in pain: detrimental and protective roles in pathogenesis and resolution of pain. Neuron, 2018, 100(6): 1292-1311.
28. Abdel-Haq R, Schlachetzki JCM, Glass CK, et al. Microbiome-microglia connections via the gut-brain axis. J Exp Med, 2019, 216(1): 41-59.
29. Ji RR, Chamessian A, Zhang YQ. Pain regulation by non-neuronal cells and inflammation. Science, 2016, 354(6312): 572-577.
30. Chiu IM. Infection, pain, and itch. Neurosci Bull, 2018, 34(1): 109-119.
31. Perez-Burgos A, Wang L, McVey Neufeld KA, et al. The TRPV1 channel in rodents is a major target for antinociceptive effect of the probiotic Lactobacillus reuteri DSM 17938. J Physiol, 2015, 593(17): 3943-3957.
32. Miller RE, Ishihara S, Tran PB, et al. An aggrecan fragment drives osteoarthritis pain through Toll-like receptor 2. JCI Insight, 2018, 3(6): e95704. doi: 10.1172/jci.insight.95704.
33. Liu T, Gao YJ, Ji RR. Emerging role of Toll-like receptors in the control of pain and itch. Neurosci Bull, 2012, 28(2): 131-144.
34. Diogenes A, Ferraz CC, Akopian AN, et al. LPS sensitizes TRPV1 via activation of TLR4 in trigeminal sensory neurons. J Dent Res, 2011, 90(6): 759-764.
35. Maruyama K, Takayama Y, Sugisawa E, et al. The ATP transporter VNUT mediates induction of dectin-1-triggered candida nociception. iScience, 2018, 6: 306-318.
36. Tang Y, Du J, Wu H, et al. Potential therapeutic effects of short-chain fatty acids on chronic pain. Curr Neuropharmacol, 2024, 22(2): 191-203.
37. Kukkar A, Singh N, Jaggi AS. Attenuation of neuropathic pain by sodium butyrate in an experimental model of chronic constriction injury in rats. J Formos Med Assoc, 2014, 113(12): 921-928.
38. Su X, Gao Y, Yang R. Gut microbiota derived bile acid metabolites maintain the homeostasis of gut and systemic immunity. Front Immunol, 2023, 14: 1127743. doi: 10.3389/fimmu.2023.1127743.
39. Lieu T, Jayaweera G, Zhao P, et al. The bile acid receptor TGR5 activates the TRPA1 channel to induce itch in mice. Gastroenterology, 2014, 147(6): 1417-1428.
40. Nagy-Grócz G, Spekker E, Vécsei L. Kynurenines, neuronal excitotoxicity, and mitochondrial oxidative stress: role of the intestinal flora. Int J Mol Sci, 2024, 25(3): 1698. doi: 10.3390/ijms25031698.
41. Resta F, Masi A, Sili M, et al. Kynurenic acid and zaprinast induce analgesia by modulating HCN channels through GPR35 activation. Neuropharmacology, 2016, 108: 136-143.
42. Pokusaeva K, Johnson C, Luk B, et al. GABA-producing Bifidobacterium dentium modulates visceral sensitivity in the intestine. Neurogastroenterol Motil, 2017, 29(1): e12904. doi: 10.1111/nmo.12904.
43. Abd-Elsayed A, Vardhan S, Aggarwal A, et al. Mechanisms of action of dorsal root ganglion stimulation. Int J Mol Sci, 2024, 25(7): 3591. doi: 10.3390/ijms25073591.
44. Haq S, Grondin JA, Khan WI. Tryptophan-derived serotonin-kynurenine balance in immune activation and intestinal inflammation. FASEB J, 2021, 35(10): e21888. doi: 10.1096/fj.202100702R.
45. Menni A, Moysidis M, Tzikos G, et al. Looking for the ideal probiotic healing regime. Nutrients, 2023, 15(13): 3055. doi: 10.3390/nu15133055.
46. York AG, Skadow MH, Oh J, et al. IL-10 constrains sphingolipid metabolism to limit inflammation. Nature, 2024, 627(8004): 628-635.
47. Khan J, Puchimada B, Kadouri D, et al. The anti-nociceptive effects of Porphyromonas gingivalis lipopolysaccharide. Arch Oral Biol, 2019, 102: 193-198.
48. Dubey AK, Podia M, Priyanka None, et al. Insight into the beneficial role of lactiplantibacillus plantarum supernatant against bacterial infections, oxidative stress, and wound healing in A549 cells and BALB/c mice. Front Pharmacol, 2021, 12: 728614. doi: 10.3389/fphar.2021.728614.
49. Panagiotou D, Filidou E, Gaitanidou M, et al. Role of Lactiplantibacillus plantarum UBLP-40, Lactobacillus rhamnosus UBLR-58 and Bifidobacterium longum UBBL-64 in the wound healing process of the excisional skin. Nutrients, 2023, 15(8): 1822. doi: 10.3390/nu15081822.
50. Tarapatzi G, Filidou E, Kandilogiannakis L, et al. The Probiotic Strains Bifidοbacterium lactis, Lactobacillus acidophilus, Lactiplantibacillus plantarum and Saccharomyces boulardii Regulate Wound Healing and Chemokine Responses in Human Intestinal Subepithelial Myofibroblasts. Pharmaceuticals (Basel), 2022, 15(10): 1293. doi: 10.3390/ph15101293.
51. Yoshimura A, Aki D, Ito M. SOCS, SPRED, and NR4a: Negative regulators of cytokine signaling and transcription in immune tolerance. Proc Jpn Acad Ser B Phys Biol Sci, 2021, 97(6): 277-291.
52. Vale GC, Mota BIS, Ando-Suguimoto ES, et al. Effect of Probiotics Lactobacillus acidophilus and Lacticaseibacillus rhamnosus on Antibacterial Response Gene Transcription of Human Peripheral Monocytes. Probiotics Antimicrob Proteins, 2023, 15(2): 264-274.
53. Altaib H, Nakamura K, Abe M, et al. Differences in the concentration of the fecal neurotransmitters GABA and glutamate are associated with microbial composition among healthy human subjects. Microorganisms, 2021, 9(2): 378. doi: 10.3390/microorganisms9020378.
54. Ferrés-Amat E, Espadaler-Mazo J, Calvo-Guirado JL, et al. Probiotics diminish the post-operatory pain following mandibular third molar extraction: a randomised double-blind controlled trial (pilot study). Benef Microbes, 2020, 11(7): 631-639.
55. Fuller AM, Bharde S, Sikandar S. The mechanisms and management of persistent postsurgical pain. Front Pain Res (Lausanne), 2023, 4: 1154597. doi: 10.3389/fpain.2023.1154597.
56. McVey Neufeld KA, Strain CR, Pusceddu MM, et al. Lactobacillus rhamnosus GG soluble mediators ameliorate early life stress-induced visceral hypersensitivity and changes in spinal cord gene expression. Neuronal Signal, 2020, 4(4): NS20200007. doi: 10.1042/NS20200007.
57. Liu YW, Wang YP, Yen HF, et al. Lactobacillus plantarum PS128 Ameliorated visceral hypersensitivity in rats through the gut-brain axis. Probiotics Antimicrob Proteins, 2020, 12(3): 980-993.
58. Ringel-Kulka T, Goldsmith JR, Carroll IM, et al. Lactobacillus acidophilus NCFM affects colonic mucosal opioid receptor expression in patients with functional abdominal pain—a randomised clinical study. Aliment Pharmacol Ther, 2014, 40(2): 200-207.

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Latest ArticlesAdvances in the study of gut microbiota and postoperative pain：mechanisms and prospects for clinical application

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