Investigating new targets for the treatment of sepsis-associated encephalopathy based on gut microbiota

doi:10.3877/cma.j.issn.2096-1537.2025.01.007

Abstract

Abstract:

Sepsis-associated encephalopathy （SAE） is a common complication in critically ill patients，and its pathogenesis is complex and lacks specific treatment. In recent years，gut flora has been found to regulate neuroinflammation and blood-brain barrier function through the “gut-brain axis”，which has become a new direction for SAE intervention. In this paper，we review the role of gut dysbiosis in SAE，explore the therapeutic strategies of probiotics，fecal transplants，and targeting of bacterial metabolites and signaling pathways，and future research should integrate multi-omics techniques with clinical translational validation.

Key words: Gut microbiota, Gut metabolites, Sepsis-associated encephalopathy, Therapeutic targets

Weifeng Shang, Dechang Chen. Investigating new targets for the treatment of sepsis-associated encephalopathy based on gut microbiota[J]. Chinese Journal of Critical Care & Intensive Care Medicine(Electronic Edition), 2025, 11(01): 31-35.

/ / Recommend

Add to citation manager EndNote|Ris|BibTeX

URL: https://icu.cma-cmc.com.cn/EN/10.3877/cma.j.issn.2096-1537.2025.01.007

https://icu.cma-cmc.com.cn/EN/Y2025/V11/I01/31

References 44

1	Hunt A. Sepsis：an overview of the signs，symptoms，diagnosis，treatment and pathophysiology ［J］. Emerg Nurse，2019，27（5）：32-41.
2	Gofton TE，Young GB. Sepsis-associated encephalopathy ［J］. Nat Rev Neurol，2012，8（10）：557-566.
3	Huang Y，Chen R，Jiang L，et al. Basic research and clinical progress of sepsis-associated encephalopathy ［J］. J Intensive Med，2021，1（2）：90-95.
4	Mazeraud A，Righy C，Bouchereau E，et al. Septic-associated encephalopathy：a comprehensive review ［J］. Neurotherapeutics，2020，17（2）：392-403.
5	Martin CR，Osadchiy V，Kalani A，et al. The brain-gut-microbiome axis ［J］. Cell Mol Gastroenterol Hepatol，2018，6（2）：133-148.
6	Wang Ⅹ，Wen Ⅹ，Yuan S，et al. Gut-brain axis in the pathogenesis of sepsis-associated encephalopathy ［J］. Neurobiol Dis，2024，195：106499.
7	Zhao L，Gao Y，Guo S，et al. Sepsis-associated encephalopathy：insight into injury and pathogenesis ［J］. CNS Neurol Disord Drug Targets，2021，20（2）：112-124.
8	Li Z，Zhang F，Sun M，et al. The modulatory effects of gut microbes and metabolites on blood-brain barrier integrity and brain function in sepsis-associated encephalopathy ［J］. PeerJ，2023，11：e15122.
9	Ⅹu J，Lu C，Liu Z，et al. Schizandrin B protects LPS-induced sepsis via TLR4/NF-κB/MyD88 signaling pathway ［J］. Am J Transl Res，2018，10（4）：1155-1163.
10	朱丹丹，于健，陆莹莹. 脓毒症相关性脑病的发病机制和潜在脑损伤标志物［J］. 实用休克杂志（中英文），2019，3（3）：171-175.
11	Adelman MW，Woodworth MH，Langelier C，et al. The gut microbiome's role in the development，maintenance，and outcomes of sepsis ［J］. Crit Care，2020，24（1）：278.
12	Muratsu A，Ikeda M，Shimizu K，et al. Dynamic change of fecal microbiota and metabolomics in a polymicrobial murine sepsis model［J］. Acute Med Surg，2022，9（1）：e770.
13	Loh JS，Mak WQ，Tan L，et al. Microbiota-gut-brain axis and its therapeutic applications in neurodegenerative diseases ［J］. Signal Transduct Target Ther，2024，9（1）：37.
14	Zhang H，Ⅹu J，Wu Q，et al. Gut microbiota mediates the susceptibility of mice to sepsis-associated encephalopathy by butyric acid ［J］. J Inflamm Res，2022，15：2103-2119.
15	Liao H，Li H，Bao H，et al. Short chain fatty acids protect the cognitive function of sepsis associated encephalopathy mice via GPR43 ［J］.Front Neurol，2022，13：909436.
16	Luo A，Li S，Wang Ⅹ，et al. Cefazolin improves anesthesia and surgery-induced cognitive impairments by modulating blood-brain barrier function，gut bacteria and short chain fatty acids ［J］. Front Aging Neurosci，2021，13：748637.
17	Doroszkiewicz J，Groblewska M，Mroczko B. The role of gut microbiota and gut-brain interplay in selected diseases of the central nervous system ［J］. Int J Mol Sci，2021，22（18）：10028.
18	Fock E，Parnova R. Mechanisms of blood-brain barrier protection by microbiota-derived short-chain fatty acids ［J］. Cells，2023，12（4）：657.
19	Sadler R，Cramer JV，Heindl S，et al. Short-chain fatty acids improve poststroke recovery via immunological mechanisms ［J］. J Neurosci，2020，40（5）：1162-1173.
20	Rose S，Bennuri SC，Davis JE，et al. Butyrate enhances mitochondrial function during oxidative stress in cell lines from boys with autism ［J］.Transl Psychiatry，2018，8（1）：42.
21	Zhou Y，Chen Y，He H，et al. The role of the indoles in microbiotagut-brain axis and potential therapeutic targets：a focus on human neurological and neuropsychiatric diseases ［J］. Neuropharmacology，2023，239：109690.
22	杨瑾，韦瑶，金钧. 胆汁酸与肠道菌群的相互作用及对脓毒症的影响［J］. 内科理论与实践，2024，19（3）：207-211.
23	刘艺，菅原蓁，吴彩军，等. 关注脓毒症脑病，改善脓毒症预后［J］.中华急诊医学杂志，2023，32（6）：719-723.
24	Liu Ⅹ，Chen L，Peng W，et al. Th17/Treg balance：the bloom and wane in the pathophysiology of sepsis ［J］. Front Immunol，2024，15：1356869.
25	Luo A，Leach ST，Barres R，et al. The microbiota and epigenetic regulation of T helper 17/regulatory t cells：in search of a balanced immune system ［J］. Front Immunol，2017，8：417.
26	Shakhar K，Shakhar G. Why do we feel sick when infected--can altruism play a role？［J］. PLoS Biol，2015，13（10）：e1002276.
27	Yoo BB，Mazmanian SK. The enteric network：interactions between the immune and nervous systems of the gut ［J］. Immunity，2017，46（6）：910-926.
28	Tan AH，Lim SY，Lang AE. The microbiome-gut-brain axis in Parkinson disease - from basic research to the clinic ［J］. Nat Rev Neurol，2022，18（8）：476-495.
29	孙丽薇，耿倩，郑国华. 肠道菌群-肠-脑-肌轴信号交流的研究进展［J］. 微生物学报，2024，64（5）：1364-1377.
30	李娜，李志峰，项辉，等. 迷走神经刺激对脓毒症相关性脑病大鼠的保护作用［J］. 中华危重病急救医学，2015，27（6）：509-513.
31	Costeloe K，Hardy P，Juszczak E，et al. Bifidobacterium breve BBG-001 in very preterm infants：a randomised controlled phase 3 trial ［J］.Lancet，2016，387（10019）：649-660.
32	Millar M，Seale J，Greenland M，et al. The microbiome of infants recruited to a randomised placebo-controlled probiotic trial （PiPS trial）［J］. EBioMedicine，2017，20：255-262.
33	Didari T，Solki S，Mozaffari S，et al. A systematic review of the safety of probiotics ［J］. Expert Opin Drug Saf，2014，13（2）：227-239.
34	Liu J，Jin Y，Li H，et al. Probiotics exert protective effect against sepsis-induced cognitive impairment by reversing gut microbiota abnormalities ［J］. J Agric Food Chem，2020，68（50）：14874-14883.
35	Wang L，Zhao R，Li Ⅹ，et al. Lactobacillus rhamnosus GG improves cognitive impairments in mice with sepsis ［J］. PeerJ，2024，12：e17427.
36	Vindigni SM，Surawicz CM. Fecal microbiota transplantation ［J］.Gastroenterol Clin North Am，2017，46（1）：171-185.
37	Qin H，Fu Y，Deng C，et al. The role of gut microbiota and the gut-lung axis in sepsis：a case study of a pregnant woman with severe rickettsial pneumonia and septic shock complicated by MODS ［J］. Clin Case Rep，2024，12（6）：e8815.
38	Li S，Guo H，Ⅹu Ⅹ，et al. Therapeutic methods for gut microbiota modification in lipopolysaccharide-associated encephalopathy ［J］.Shock，2021，56（5）：824-831.
39	Baxter M，Ahmad T，Colville A，et al. Fatal aspiration pneumonia as a complication of fecal microbiota transplant ［J］. Clin Infect Dis，2015，61（1）：136-137.
40	DeFilipp Z，Bloom PP，Torres Soto M，et al. Drug-resistant E. coli bacteremia transmitted by fecal microbiota transplant ［J］. N Engl J Med，2019，381（21）：2043-2050.
41	Huang ZB，Zhang GP，Lu CⅩ，et al. Gut microbiota-derived 3-indoleacetic acid confers a protection against sepsis-associated encephalopathy through microglial aryl hydrocarbon receptors ［J］. Exp Neurol，2025，384：115055.
42	Ⅹu Y，Shen B，Pan Ⅹ，et al. Palmatine ameliorated lipopolysaccharideinduced sepsis-associated encephalopathy mice by regulating the microbiota-gut-brain axis ［J］. Phytomedicine，2024，124：155307.
43	Chen L，Qing W，Yi Z，et al. NU9056，a KAT 5 inhibitor，treatment alleviates brain dysfunction by inhibiting NLRP3 inflammasome activation，affecting gut microbiota，and derived metabolites in LPStreated mice ［J］. Front Nutr，2021，8：701760.
44	Li S，Lv J，Li J，et al. Intestinal microbiota impact sepsis associated encephalopathy via the vagus nerve ［J］. Neurosci Lett，2018，662：98-104.

[1]	Jin Yang, Xueke Liu, Yuanyuan Zhang, Jun Jin, Yao Wei. Protective effect of gut microbiota-derived lithocholic acid on sepsis-associated hepatic injury [J]. Chinese Journal of Critical Care Medicine(Electronic Edition), 2024, 17(04): 265-274.
[2]	Shiyang Yu, Dagang Yang, Yongning Li, Xianqiu Xiong, Futang Li, Rong Wang. Accelerated rehabilitation surgery in obstructive jaundice：metabolic interactions between bile acids and intestinal microbes [J]. Chinese Journal of Operative Procedures of General Surgery(Electronic Edition), 2023, 17(02): 230-234.
[3]	Daocheng Fang, Chunhua Tang, Yuanyuan Hu. The effect of gut microbiota on the formation of calcium oxalate kidney stones [J]. Chinese Journal of Endourology(Electronic Edition), 2024, 18(05): 509-513.
[4]	Junnan Wang, Ye Liu, Ruohan Li, Qingsong Ye. The potential of mesenchymal stem cells in regulating the gut-brain axis in the treatment of neurological diseases [J]. Chinese Journal of Cell and Stem Cell(Electronic Edition), 2024, 14(05): 313-319.
[5]	Xinxin Hu, Xiaofan Meng, Zhaoan Guo. Research progress on the pathogenesis of hypertensive nephropathy [J]. Chinese Journal of Kidney Disease Investigation(Electronic Edition), 2023, 12(06): 339-343.
[6]	Xiaomei Qiao, Kaili Kong, Jingai Fang, Xiaodong Zhang. Research progress on the relationship between the "gut-skin axis" and the uremic skin lesions [J]. Chinese Journal of Kidney Disease Investigation(Electronic Edition), 2023, 12(05): 291-294.
[7]	Na Li, Guozhen Zhu. Progress of research on the roles of gut microbiota and its metabolites in acute kidney injury [J]. Chinese Journal of Kidney Disease Investigation(Electronic Edition), 2023, 12(04): 215-219.
[8]	Ning Wang, Yanzhe Liu, Ziying Wu, Chao Zeng, Guanghua Lei, Tingting Sha, Yilun Wang. Causal associations of gut Microbiota with phenotype indicators of sarcopenia: A mendelian randomization study [J]. Chinese Journal of Geriatric Orthopaedics and Rehabilitation(Electronic Edition), 2023, 09(06): 333-342.
[9]	Jiyun Hu, Shucai Xie, Lina Zhang. Advancement of S100 calcium binding protein B in neurocritical care field [J]. Chinese Journal of Critical Care & Intensive Care Medicine(Electronic Edition), 2023, 09(03): 298-303.
[10]	Yan Wang, Haiqian Liang, Shanshan Guo. Research advances in role of inflammasome in traumatic brain injury [J]. Chinese Journal of Brain Diseases and Rehabilitation(Electronic Edition), 2024, 14(03): 177-181.
[11]	Xiao Qu, Liang Wang, Ping Lu, Bin He, Min Sun. Correlation analysis of inflammatory factors in peripheral blood and characteristics of Gut microbiota with the condition of patients with active Ulcerative colitis [J]. Chinese Journal of Digestion and Medical Imageology(Electronic Edition), 2023, 13(06): 466-470.
[12]	Peng Sheng, Lizhe1 Bai, Jing Zhang, Dan Li, Hong Cao. Galactooligosaccharides enhance intestinal barrier function and mitigate bone loss in ovariectomized mice [J]. Chinese Journal of Clinicians(Electronic Edition), 2025, 19(01): 48-57.
[13]	Lu Bai, Qingxia Li, Yizhuo Feng, Xueqian Liu, Ruoqi Liu, Zhuomin Qu, Lingxia Zhao. Advances in treatment of diabetic kidney disease with butyrate [J]. Chinese Journal of Clinicians(Electronic Edition), 2024, 18(03): 303-308.
[14]	Meiju Wei, Ling Pan. Role of gut microbiota-bile acid metabolism axis in chronic kidney disease [J]. Chinese Journal of Clinicians(Electronic Edition), 2024, 18(02): 219-222.
[15]	Zeping Jin, Jing Dong, Yunpeng Liu, Yang Wang. Correlation between microbiota-gut-brain axis and the risk factors of ischemic stroke [J]. Chinese Journal of Cerebrovascular Diseases(Electronic Edition), 2023, 17(05): 510-517.

Please choose a citation manager

Content to export