肠道菌群与老年危重症

doi:10.3969/j.issn.1003-9198.2025.05.004

摘要/Abstract

摘要： 肠道菌群是人体的“第二基因组”,其多样性及功能稳态对维持宿主健康至关重要。老年人因生理功能衰退、脓毒症等疾病及药物使用等因素,更易出现肠道菌群失衡,进而影响免疫调节、代谢稳态及炎症反应,显著增加危重症发生率和死亡率。本文系统阐述肠道菌群在免疫调节、代谢稳态及屏障保护中的核心功能,分析老年人群菌群失衡的流行病学特征及其与危重症的关联机制,重点探讨菌群代谢产物(如短链脂肪酸、胆汁酸、色氨酸衍生物)通过“肠-器官轴”调控危重症病理进程的研究进展。最后,展望靶向菌群干预策略在老年危重症防治中的临床应用潜力。

关键词: 老年人, 危重症, 肠道菌群, 肠-器官轴, 菌群干预

Abstract: The gut microbiota is the second genome of the human body, which plays a crucial role in maintaining host health through its diversity and functional homeostasis. Elderly populations are more prone to gut microbiota imbalance due to physiological decline, diseases such as sepsis and medication use, which can affect immune regulation, metabolic homeostasis, and inflammatory responses, significantly increasing the incidence and mortality of critical illnesses. This article systematically reviews the core functions of the gut microbiota in immune modulation, metabolic balance, and barrier protection, analyzes the epidemiological characteristics of microbiota dysbiosis in the elderly and its association with critical illnesses, and focuses on the research progress of how microbial metabolites (such as, short-chain fatty acids, bile acids, and tryptophan derivatives) regulate the pathological processes of severe condition via the “gut-organ axis.” Finally, it looks forward to the clinical potential of targeted microbiota interventions for preventing and managing critical illnesses in the elderly.

Key words: aged, critical illness, gut microbiota, gut-organ axis, microbiota intervention

中图分类号:

R 372
R 592

段剑锋, 虞文魁. 肠道菌群与老年危重症[J]. 实用老年医学, 2025, 39(5): 450-455.

DUAN Jianfeng, YU Wenkui. Gut microbiota and critical illness in the elderly[J]. Practical Geriatrics, 2025, 39(5): 450-455.

参考文献

[1] VALLET H, SCHWARZ G L, FLAATTEN H, et al. Mortality of older patients admitted to an ICU: a systematic review[J]. Crit Care Med,2021,49(2):324-334.
[2] CLAESSON M J, CUSACK S, O'SULLIVAN O, et al. Composition, variability, and temporal stability of the intestinal microbiota of the elderly[J]. Proc Natl Acad Sci USA, 2011,108( Suppl 1):4586-4591.
[3] VICTORIA M, ELENA V B, AMPARO G N, et al. Gut microbiota alterations in critically ill older patients: a multicenter study[J]. BMC Geriatr,2022,22(1):373.
[4] BATTAGLINI D, TORRES A. Gut microbiota and its impact on critical illness[J]. Curr Opin Crit Care,2025,31(2):189-197.
[5] ODAMAKI T, KATO K, SUGAHARA H, et al. Age-related changes in gut microbiota composition from newborn to centenarian: a cross-sectional study[J]. BMC Microbiol, 2016,16:90.
[6] BLAUT M. Gut microbiota and energy balance: role in obesity[J]. Proc Nutr Soc,2015,74(3):227-234.
[7] BHATTARAI Y, WILLIAMS B B, BATTAGLIOLI E J, et al. Gut microbiota-produced tryptamine activates an epithelial g-protein-coupled receptor to increase colonic secretion[J]. Cell Host Microbe,2018,23(6):775-785.e5.
[8] XU H, FANG F, WU K, et al. Gut microbiota-bile acid crosstalk regulates murine lipid metabolism via the intestinal FXR-FGF19 axis in diet-induced humanized dyslipidemia[J]. Microbiome,2023,11(1):262.
[9] WON T H, ARIFUZZAMAN M, PARKHURST C N, et al. Host metabolism balances microbial regulation of bile acid signalling[J]. Nature,2025,638(8049):216-224.
[10] MINIET A A, GRUNWELL J R,COOPERSMITH C M. The microbiome and the immune system in critical illness[J]. Curr Opin Crit Care,2021,27(2):157-163.
[11] CLEMENTE J C, URSELL L K, PARFREY L W, et al. The impact of the gut microbiota on human health: an integrative view[J]. Cell,2012,148(6):1258-1270.
[12] SCHNUPF P, GABORIAU-ROUTHIAU V, SANSONETTI P J, et al. Segmented filamentous bacteria, Th17 inducers and helpers in a hostile world[J]. Curr Opin Microbiol,2017,35:100-109.
[13] PLUZNICK J L, PROTZKO R J, GEVORGYAN H, et al. Olfactory receptor responding to gut microbiota-derived signals plays a role in renin secretion and blood pressure regulation[J]. Proc Natl Acad Sci USA,2013,110(11):4410-4415.
[14] XU Y, DUAN J, WANG D, et al. Akkermansia muciniphila alleviates persistent inflammation, immunosuppression, and catabolism syndrome in mice[J]. Metabolites,2023,13(2):194.
[15] KAYAMA H, TAKEDA K. Polysaccharide a of bacteroides fragilis: actions on dendritic cells and T cells[J]. Mol Cell,2014,54(2):206-207.
[16] MARTINEZ F A C, BALCIUNAS E M, CONVERTI A, et al. Bacteriocin production by Bifidobacterium spp. A review[J]. Biotechnol Adv, 2013,31(4):482-488.
[17] POWELL N, WALKER M M, TALLEY N J. The mucosal immune system: master regulator of bidirectional gut-brain communications[J]. Nat Rev Gastroenterol Hepatol,2017,14(3):143-159.
[18] BONAZ B, BAZIN T, PELLISSIER S. The vagus nerve at the interface of the microbiota-gut-brain axis[J]. Front Neurosci,2018,12:49.
[19] TIWARI S, PARAMANIK V. Role of probiotics in depression: connecting dots of gut-brain-axis through hypothalamic-pituitary adrenal axis and tryptophan/kynurenic pathway involving indoleamine-2,3-dioxygenase[J]. Mol Neurobiol,2025.Online ahead of print.
[20] 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.
[21] XU K, GAO X, XIA G, et al. Rapid gut dysbiosis induced by stroke exacerbates brain infarction in turn[J]. Gut,2021:gutjnl-2020-323263..
[22] ANAND S, MANDE S S. Diet, microbiota and gut-lung connection[J]. Front Microbiol, 2018,9:2147.
[26] ELADHAM M W, SELVAKUMAR B, SAHEB SHARIF-ASKARI N, et al. Unraveling the gut-Lung axis: exploring complex mechanisms in disease interplay[J]. Heliyon,2024,10(1):e24032.
[24] LI X, SHANG S, WU M, SONG Q ,et al. Gut microbial metabolites in lung cancer development and immunotherapy: Novel insights into gut-lung axis[J]. Cancer Lett,2024,598:217096.
[25] MCALEER J P , KOLLS J K. Contributions of the intestinal microbiome in lung immunity[J]. Eur J Immunol,2018,48(1):39-49.
[26] REN Z, ZHENG Z,FENG X. Role of gut microbes in acute lung injury/acute respiratory distress syndrome[J]. Gut Microbes,2024,16(1):2440125.
[27] ADDOLORATO G, PONZIANI F R, DIONISI T, et al. Gut microbiota compositional and functional fingerprint in patients with alcohol use disorder and alcohol-associated liver disease[J]. Liver Int,2020,40(4):878-888.
[28] CHEN Y, JI F, GUO J, et al. Dysbiosis of small intestinal microbiota in liver cirrhosis and its association with etiology[J]. Sci Rep,2016,6:34055.
[29] TILG H, ADOLPH T E,TRAUNER M. Gut-liver axis: pathophysiological concepts and clinical implications[J]. Cell Metab,2022,34(11):1700-1718.
[30] Kim G, Chen Z, Li J, et al. Gut-liver axis calibrates intestinal stem cell fitness[J]. Cell, 2024,187(4):914-930.e20.
[31] ZHU W, GREGORY J C, ORG E, et al. Gut microbial metabolite TMAO enhances platelet hyperreactivity and thrombosis risk[J]. Cell,2016,165(1):111-124.
[32] ANDRADE-OLIVEIRA V, AMANO M T, CORREA-COSTA M, et al. Gut bacteria products prevent AKI induced by ischemia-reperfusion[J]. J Am Soc Nephrol,2015,26(8):1877-1888.
[33] WU J, REN W, CHEN L, et al. Age-related changes in the composition of intestinal microbiota in elderly chinese individuals[J]. Gerontology,2022,68(9):976-988.
[34] SCHLECHTE J, ZUCOLOTO A Z, YU I L, et al. Dysbiosis of a microbiota-immune metasystem in critical illness is associated with nosocomial infections[J]. Nat Med, 2023,29(4):1017-1027.
[35] MCDONALD D, ACKERMANN G, KHAILOVA L, et al. Extreme dysbiosis of the microbiome in critical illness[J]. mSphere,2016,1(4): e00199-16.
[36] LANKELMA J M, VAN VUGHT L A, BELZER C, et al. Critically ill patients demonstrate large interpersonal variation in intestinal microbiota dysregulation: a pilot study[J]. Intensive Care Med,2017,43:59-68.
[37] THEVARANJAN N, PUCHTA A, SCHULZ C, et al. Age-associated microbial dysbiosis promotes intestinal permeability, systemic inflammation, and macrophage dysfunction [J]. Cell Host Microbe, 2017,21(4):455-466.e4.
[38] NIKOLICH-ŽUGICH J. The twilight of immunity: emerging concepts in aging of the immune system[J]. Nat Immunol,2018,19(1): 10-19.
[39] MOHAMMADI F, RUDKOWSKA I. Dietary lipids, gut microbiota, and their metabolites: insights from recent studies[J]. Nutrients, 2025,17(4): 639.
[40] LADOPOULOS T, GIANNAKI M, ALEXOPOULOU C, et al. Gastrointestinal dysmotility in critically ill patients[J]. Ann Gastroenterol,2018,31(3):273-281.
[41] MORON R, GALVEZ J, COLMENERO M, et al. The importance of the microbiome in critically ill patients: role of nutrition[J]. Nutrients,2019,11(12): 3002.
[42] SALAMEH T J, ROTH K, SCHULTZ L, et al. Gut microbiome dynamics and associations with mortality in critically ill patients[J]. Gut Pathog,2023,15(1):66.
[43] ADELMAN M W, WOODWORTH M H, LANGELIER C, et al. The gut microbiome's role in the development, maintenance, and outcomes of sepsis[J]. Crit Care,2020,24(1):278.
[44] MILLER W D, KESKEY R, ALVERDY J C. Sepsis and the microbiome: a vicious cycle[J]. J Infect Dis,2021,223(12 Suppl 2):S264-s269.
[45] XIONG D, GENG H, LV X, et al. Inflammatory response and anti-inflammatory treatment in persistent inflammation-immunosuppression-catabolism syndrome (PICS)[J]. J Inflamm Res,2025,18:2267-2281.
[46] DAVISON J M, WISCHMEYER P E. Probiotic and synbiotic therapy in the critically ill: state of the art[J]. Nutrition,2019,59:29-36.
[47] WOZNIAK H, BECKMANN T S, FRÖHLICH L, et al. The central and biodynamic role of gut microbiota in critically ill patients[J]. Crit Care, 2022,26(1):250.
[48] SCHÖRGHUBER M, FRUHWALD S. Effects of enteral nutrition on gastrointestinal function in patients who are critically ill[J]. Lancet Gastroenterol Hepatol,2018,3(4):281-287.
[49] HE S, LIN F, HU X, et al. Gut microbiome-based therapeutics in critically ill adult patients-a narrative review[J]. Nutrients,2023,15(22):4734.
[50] KESKEY R, CONE J T, DEFAZIO J R,et al. The use of fecal microbiota transplant in sepsis[J]. Transl Res, 2020,226:12-25.
[51] PANCHE A N, DIWAN A D, CHANDRA S R. Flavonoids: an overview[J]. J Nutr Sci, 2016,5:e47.
[52] LI J, ZHANG L, WU T, et al. Indole-3-propionic acid improved the intestinal barrier by enhancing epithelial barrier and mucus barrier[J]. J Agric Food Chem, 2021,69(5):1487-1495.