老年肠源性脓毒症的研究进展

doi:10.3969/j.issn.1003-9198.2025.04.003

摘要/Abstract

摘要： 肠道是导致脓毒症第二常见的感染来源,而衰老引起的肠道病理生理改变可能是老年病人肠源性脓毒症易感易危的可能原因。本文分析了老年病人肠道免疫功能、黏膜屏障状态、肠道微生物群构成与脓毒症发生发展之间的联系,同时综述了相关预防和治疗进展,提示未来研究应聚焦于衰老与肠道微环境的动态互作机制,开发靶向肠道屏障修复和免疫调节的新型疗法,并通过大样本临床研究优化现有干预手段,以降低老年肠源性脓毒症的发病率及死亡率。

关键词: 肠源性脓毒症, 老年人, 防治措施

Abstract: The gut is the second most common source of sepsis, and age-related pathophysiological alterations in the gut may serve as potential contributors to the susceptibility and vulnerability in the elderly patients with enterogenic sepsis. This article analyzes the relationship between gut immune function, mucosal barrier integrity, gut microbiota composition and the pathogenesis of sepsis in the elderly. It further reviews recent advances in prevention and therapeutic strategies, and suggests that future research should focus on elucidating the dynamic interactions between aging and the intestinal microenvironment, developing novel therapies targeting gut barrier restoration and immunomodulation, and optimizing existing clinical interventions through large-scale trials, with the ultimate aim of reducing the incidence and mortality of enterogenic sepsis in the elderly.

Key words: enterogenic sepsis, aged, prevention and control measures

中图分类号:

R 631

孙宇新, 陈明泉. 老年肠源性脓毒症的研究进展[J]. 实用老年医学, 2025, 39(4): 336-340.

SUN Yuxin, CHEN Mingquan. Reaserch advances in enterogenic sepsis in the elderly[J]. Practical Geriatrics, 2025, 39(4): 336-340.

参考文献

[1] CECCONI M, EVANS L, LEVY M, et al. Sepsis and septic shock[J].Lancet, 2018, 392(10141):75-87.
[2] IBARZ M, HAAS L E M, CECCATO A, et al. The critically ill older patient with sepsis: a narrative review[J].Ann Intensive Care, 2024, 14(1):6.
[3] KOTFIS K, WITTEBOLE X, JASCHINSKI U, et al. A worldwide perspective of sepsis epidemiology and survival according to age: observational data from the ICON audit[J].J Crit Care, 2019, 51:122-132.
[4] ALHAMYANI A H, ALAMRI M S, ALJUAID N W, et al. Sepsis inaging populations: a review of risk factors, diagnosis, and management[J].Cureus, 2024, 16(12):e74973.
[5] VANCAMELBEKE M, VERMEIRE S. The intestinal barrier: a fundamental role in health and disease[J].Expert Rev Gastroenterol Hepatol, 2017, 11(9):821-834.
[6] SALAZAR A M, APARICIO R, CLARK R I, et al. Intestinal barrier dysfunction: an evolutionarily conserved hallmark of aging[J].Dis Model Mech, 2023, 16(4):dmm049969.
[7] KATZ D, HOLLANDER D, SAID H M, et al. Aging-associated increase in intestinal permeability to polyethylene glycol 900[J].Dig Dis Sci, 1987, 32(3):285-288.
[8] MA T Y, HOLLANDER D, DADUFALZA V, et al. Effect of aging and caloric restriction on intestinal permeability[J].Exp Gerontol, 1992, 27(3):321-333.
[9] TRAN L, GREENWOOD-VAN MEERVELD B. Age-associated remodeling of the intestinal epithelial barrier[J].J Gerontol A Biol Sci Med Sci, 2013, 68(9):1045-1056.
[10]MITCHELL E L, DAVIS A T, BRASS K, et al. Reduced intestinal motility, mucosal barrier function, and inflammation in aged monkeys[J].J Nutr Health Aging, 2017, 21(4):354-361.
[11]QI Y, GOEL R, KIM S, et al. Intestinal permeability biomarker zonulin is elevated in healthy aging[J].J Am Med Dir Assoc, 2017, 18(9):810.e1-810.e4.
[12]FULOP T, LARBI A, PAWELEC G, et al. Immunology of aging: the birth of inflammaging[J].Clin Rev Allergy Immunol, 2023, 64(2):109-122.
[13]NIKOLICH-ŽUGICH J. The twilight of immunity: emerging concepts in aging of the immune system[J].Nat Immunol, 2018, 19(1):10-19.
[14]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.
[15]WILSON Q N, WELLS M, DAVIS A T, et al. Greater microbial translocation and vulnerability to metabolic disease in healthy aged female monkeys[J].Sci Rep, 2018, 8(1):11373.
[16]GHOSH S S, WANG J, YANNIE P J, et al. Intestinal barrier dysfunction, LPS translocation, and disease development[J].J Endocr Soc, 2020, 4(2):bvz039.
[17]SHEMTOV S J, EMANI R, BIELSKA O, et al. The intestinal immune system and gut barrier function in obesity and ageing[J].FEBS J, 2023, 290(17):4163-4186.
[18]AMSTERDAM D, OSTROV B E. The impact of the microbiome on immunosenescence[J].Immunol Invest, 2018, 47(8):801-811.
[19]FEEHAN J, TRIPODI N, APOSTOLOPOULOS V. The twilight of the immune system:the impact of immunosenescence in aging[J].Maturitas, 2021, 147:7-13.
[20]JILL SAFFREY M. Aging of the mammalian gastrointestinal tract: a complex organ system[J].Age, 2014, 36(3):9603.
[21]CHAMBERS E S, AKBAR A N. Can blocking inflammation enhance immunity during aging?[J].J Allergy Clin Immunol, 2020, 145(5):1323-1331.
[22]WALKER E M, SLISARENKO N, GERRETS G L, et al. Inflammaging phenotype in rhesus macaques is associated with a decline in epithelial barrier-protective functions and increased pro-inflammatory function in CD161-expressing cells[J].Geroscience, 2019, 41(6):739-757.
[23]BECKER L, NGUYEN L, GILL J, et al. Age-dependent shift in macrophage polarisation causes inflammation-mediated degeneration of enteric nervous system[J].Gut, 2018, 67(5):827-836.
[24]AGRAWAL S, GANGULY S, TRAN A, et al. Retinoic acid treated human dendritic cells induce T regulatory cells via the expression of CD141 and GARP which is impaired with age[J].Aging, 2016, 8(6):1223-1235.
[25]SATO S, KIYONO H, FUJIHASHI K. Mucosa limmunosenescence in the gastrointestinal tract: a mini-review[J].Gerontology, 2015, 61(4):336-342.
[26]SANTIAGO A F, ALVES A C, OLIVEIRA R P, et al. Aging correlates with reduction in regulatory-type cytokines and T cells in the gut mucosa[J].Immunobiology, 2011, 216(10):1085-1093.
[27]SOVRAN B, HUGENHOLTZ F, ELDERMAN M, et al. Age-associated impairment of the mucus barrier function is associated with profound changes in microbiota and immunity[J].Sci Rep, 2019, 9(1):1437.
[28]KAWANISHI H, KIELY J. Immune-related alterations in aged gut-associated lymphoid tissues inmice[J].Dig Dis Sci, 1989, 34(2):175-184.
[29]MCDONALD K G, LEACH M R, HUANG C, et al. Aging impacts isolated lymphoid follicle development and function[J].Immun Ageing, 2011, 8(1):1.
[30]DILLON S M, THOMPSON T A, CHRISTIANS A J, et al. Reduced immune-regulatory molecule expression on human colonic memory CD4 T cells in older adults[J].Immun Ageing, 2021, 18(1):6.
[31]LING Z, LIU X, CHENG Y, et al. Gut microbiota and aging[J].Crit Rev Food Sci Nutr, 2022, 62(13):3509-3534.
[32]LAHTINEN S J, TAMMELA L, KORPELA J, et al. Probiotics modulate the Bifidobacterium microbiota of elderly nursing home residents[J].Age, 2009, 31(1):59-66.
[33]CLAESSON M J, JEFFERY I B, CONDE S, et al. Gut microbiota composition correlates with diet and health in the elderly[J].Nature, 2012, 488(7410):178-184.
[34]MARIAT D, FIRMESSE O, LEVENEZ F, et al. The Firmicutes/Bacteroidetes ratio of the human microbiota changes with age[J].BMC Microbiol, 2009, 9:123.
[35]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.
[36]BIAGI E, FRANCESCHI C, RAMPELLI S, et al. Gut microbiota and extreme longevity[J].Curr Biol, 2016, 26(11):1480-1485.
[37]RAMPELLI S, SOVERINI M, D’AMICO F, et al. Shotgun metagenomics of gut microbiota in humans with up to extreme longevity and the increasing role of xenobiotic degradation[J].mSystems, 2020, 5(2):e00124-20.
[38]SURAWICZ C M, MCFARLAND L V. Pseudomembranous colitis: causes and cures[J].Digestion, 1999, 60(2):91-100.
[39]FOLEY M H, WALKER M E, STEWART A K, et al. Bile salt hydrolases shape the bile acid landscape and restrict Clostridioides difficile growth in the murine gut[J].Nat Microbiol, 2023, 8(4):611-628.
[40]BUFFIE C G, BUCCI V, STEIN R R, et al. Precision microbiome reconstitution restores bile acid mediated resistance to Clostridium difficile[J].Nature, 2015, 517(7533):205-208.
[41]CHEN C N, LIAO Y H, TSAI S C, et al. Age-dependent effects of caloric restriction on mTOR and ubiquitin-proteasome pathways in skeletal muscles[J].Geroscience, 2019, 41(6):871-880.
[42]PAN F, ZHANG L, LI M, et al. Predominant gut Lactobacillus murinus strain mediates anti-inflammaging effects in calorie-restricted mice[J].Microbiome, 2018, 6(1):54.
[43]FABBIANO S,SUÁREZ-ZAMORANO N, CHEVALIER C, et al. Functional gut microbiota remodeling contributes to the caloric restriction-induced metabolic improvements[J].Cell Metab, 2018, 28(6):907-921.e7.
[44]GUILLEMARD E, TONDU F, LACOIN F, et al. Consumption of a fermented dairy product containing the probiotic Lactobacillus casei DN-114001 reduces the duration of respiratory infections in the elderly in a randomised controlled trial[J].Br J Nutr, 2010, 103(1):58-68.
[45]AHMADI S, WANG S, NAGPAL R, et al. A human-origin probiotic cocktail ameliorates aging-related leaky gut and inflammation via modulating the microbiota/taurine/tight junction axis[J].JCI Insight, 2020, 5(9):e132055.
[46]YOSHIDA N, EMOTO T, YAMASHITA T, et al.Bacteroides vulgatus and Bacteroides dorei reduce gut microbial lipopolysaccharide production and inhibit atherosclerosis[J].Circulation, 2018, 138(22):2486-2498.
[47]BÁRCENA C, VALDÉS-MAS R, MAYORAL P, et al. Healthspan and lifespan extension by fecal microbiota transplantation into progeroid mice[J].Nat Med, 2019, 25(8):1234-1242.
[48]LUO Y, TIXIER E N, GRINSPAN A M. Fecalmicrobiota transplantation for Clostridioides difficile in high-risk older adults is associated with early recurrence[J].Dig Dis Sci, 2020, 65(12):3647-3651.
[49]LOU X, XUE J, SHAO R, et al. Fecal microbiota transplantation and short-chain fatty acids reduce sepsis mortality by remodeling antibiotic-induced gut microbiota disturbances[J].Front Immunol, 2023, 13:1063543.