The possible role of gut microbiota dysbiosis in the pathophysiology of delirium in older persons

Andrea Ticinesi , Alberto Parise , Antonio Nouvenne , Nicoletta Cerundolo , Beatrice Prati , Tiziana Meschi

Microbiome Research Reports ›› 2023, Vol. 2 ›› Issue (3) : 19

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Microbiome Research Reports ›› 2023, Vol. 2 ›› Issue (3) :19 DOI: 10.20517/mrr.2023.15
Review

The possible role of gut microbiota dysbiosis in the pathophysiology of delirium in older persons

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Abstract

Delirium is a clinical syndrome characterized by an acute change in attention, awareness and cognition with fluctuating course, frequently observed in older patients during hospitalization for acute medical illness or after surgery. Its pathogenesis is multifactorial and still not completely understood, but there is general consensus on the fact that it results from the interaction between an underlying predisposition, such as neurodegenerative diseases, and an acute stressor acting as a trigger, such as infection or anesthesia. Alterations in brain insulin sensitivity and metabolic function, increased blood-brain barrier permeability, neurotransmitter imbalances, abnormal microglial activation and neuroinflammation have all been involved in the pathophysiology of delirium. Interestingly, all these mechanisms can be regulated by the gut microbiota, as demonstrated in experimental studies investigating the microbiota-gut-brain axis in dementia. Aging is also associated with profound changes in gut microbiota composition and functions, which can influence several aspects of disease pathophysiology in the host. This review provides an overview of the emerging evidence linking age-related gut microbiota dysbiosis with delirium, opening new perspectives for the microbiota as a possible target of interventions aimed at delirium prevention and treatment.

Keywords

Perioperative neurocognitive dysfunction, dementia, cognitive frailty, aging / dysbiosis, gut-brain axis, intestinal mucosa permeability

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Andrea Ticinesi, Alberto Parise, Antonio Nouvenne, Nicoletta Cerundolo, Beatrice Prati, Tiziana Meschi. The possible role of gut microbiota dysbiosis in the pathophysiology of delirium in older persons. Microbiome Research Reports, 2023, 2(3): 19 DOI:10.20517/mrr.2023.15

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References

[1]

Wilson JE,Cunningham C.Delirium.Nat Rev Dis Primers2020;6:90 PMCID:PMC9012267

[2]

Bellelli G,Di Santo SG.Italian Study Group on Delirium (ISGoD)“Delirium Day”: a nationwide point prevalence study of delirium in older hospitalized patients using an easy standardized diagnostic tool.BMC Med2016;14:106 PMCID:PMC4950237

[3]

Krewulak KD,Leigh JP,Fiest KM.Incidence and prevalence of delirium subtypes in an adult ICU: a systematic review and meta-analysis.Crit Care Med2018;46:2029-35

[4]

Featherstone I,Johnson M.Risk factors for delirium in adult patients receiving specialist palliative care: a systematic review and meta-analysis.Palliat Med2022;36:254-67

[5]

Han QYC,Klainin-Yobas P,Wu XV.Prevalence, risk factors, and impact of delirium on hospitalized older adults with dementia: a systematic review and meta-analysis.J Am Med Dir Assoc2022;23:23-32.e27

[6]

Oh ES,Hshieh TT.Delirium in older persons: advances in diagnosis and treatment.JAMA2017;318:1161-74 PMCID:PMC5717753

[7]

Stollings JL,Chanques G,Pandharipande PP.Delirium in critical illness: clinical manifestations, outcomes, and management.Intensive Care Med2021;47:1089-103 PMCID:PMC8366492

[8]

Siegel EJ.Pediatric delirium: epidemiology and outcomes.Curr Opin Pediatr2020;32:743-9

[9]

Shao SC,Chen YH,Hung MJ.Prevalence, incidence and mortality of delirium in patients with COVID-19: a systematic review and meta-analysis.Age Ageing2021;50:1445-53 PMCID:PMC8247209

[10]

Ticinesi A,Parise A.Delirium in COVID-19: epidemiology and clinical correlations in a large group of patients admitted to an academic hospital.Aging Clin Exp Res2020;32:2159-66 PMCID:PMC7498987

[11]

Morandi A,Cherubini A.ISGoD GroupClinical features associated with delirium motor subtypes in older inpatients: results of a multicenter study.Am J Geriatr Psychiatry2017;25:1064-71

[12]

Inouye SK,Saczynski JS.Delirium in elderly people.Lancet2014;383:911-22

[13]

Marcantonio ER.Delirium in hospitalized older adults.N Engl J Med2017;377:1456-66 PMCID:PMC5706782

[14]

Lynch SV.The human intestinal microbiome in health and disease.N Engl J Med2016;375:2369-79

[15]

Vaiserman AM,Marotta F.Gut microbiota: a player in aging and a target for anti-aging intervention.Ageing Res Rev2017;35:36-45

[16]

Strasser B,Weyh C,Ticinesi A.The effects of lifestyle and diet on gut microbiota composition, inflammation and muscle performance in our aging society.Nutrients2021;13:2045 PMCID:PMC8232643

[17]

Cryan JF,Cowan CSM.The microbiota-gut-brain axis.Physiol Rev2019;99:1877-2013

[18]

Sekirov I,Antunes LC.Gut microbiota in health and disease.Physiol Rev2010;90:859-904

[19]

Jandhyala SM,Subramanyam C,Sasikala M.Role of the normal gut microbiota.World J Gastroenterol2015;21:8787-803 PMCID:PMC4528021

[20]

Arumugam M,Pelletier E.MetaHIT ConsortiumEnterotypes of the human gut microbiome.Nature2011;473:174-80 PMCID:PMC3728647

[21]

Rajilić-Stojanović M.The first 1000 cultured species of the human gastrointestinal microbiota.FEMS Microbiol Rev2014;38:996-1047 PMCID:PMC4262072

[22]

Hidalgo-Cantabrana C,Ruiz L,Sánchez B.Bifidobacteria and their health-promoting effects.Microbiol Spectr2017;5

[23]

Milani C,Bottacini F.The first microbial colonizers of the human gut: composition, activities, and health implications of the infant gut microbiota.Microbiol Mol Biol Rev2017;81 PMCID:PMC5706746

[24]

Idicula DV,Parappilly SJ,Balan J.Salutary attributes of probiotic human gut lactobacilli for gut health.Lett Appl Microbiol2023;76:ovad011

[25]

Leylabadlo HE,Feizabadi MM.The critical role of Faecalibacterium prausnitzii in human health: an overview.Microb Pathog2020;149:104344

[26]

Baldelli V,Putignani L.The role of enterobacteriaceae in gut microbiota dysbiosis in inflammatory bowel diseases.Microorganisms2021;9:697 PMCID:PMC8066304

[27]

Haran JP.Aging, frailty, and the microbiome-how dysbiosis influences human aging and disease.Gastroenterology2021;160:507-23 PMCID:PMC7856216

[28]

Badal VD,Murray ER.The gut microbiome, aging, and longevity: a systematic review.Nutrients2020;12:3759 PMCID:PMC7762384

[29]

Ticinesi A,Tana C.The impact of intestinal microbiota on bio-medical research: definitions, techniques and physiology of a “new frontier”.Acta Biomed2018;89:52-9 PMCID:PMC6502191

[30]

Ling Z,Cheng Y,Wu S.Gut microbiota and aging.Crit Rev Food Sci Nutr2022;62:3509-34

[31]

Claesson MJ,Conde S.Gut microbiota composition correlates with diet and health in the elderly.Nature2012;488:178-84

[32]

Wilmanski T,Rappaport N.Gut microbiome pattern reflects healthy ageing and predicts survival in humans.Nat Metab2021;3:274-86 PMCID:PMC8169080

[33]

Mariat D,Levenez F.The Firmicutes/Bacteroidetes ratio of the human microbiota changes with age.BMC Microbiol2009;9:123 PMCID:PMC2702274

[34]

Galkin F,Aliper A.Human gut microbiome aging clock based on taxonomic profiling and deep learning.iScience2020;23:101199 PMCID:PMC7298543

[35]

Wu L,Zinellu A,Kelvin DJ.A cross-sectional study of compositional and functional profiles of gut microbiota in sardinian centenarians.mSystems2019;4 PMCID:PMC6616150

[36]

Lopetuso LR,Schiavoni M.Towards a disease-associated common trait of gut microbiota dysbiosis: the pivotal role of Akkermansia muciniphila.Dig Liver Dis2020;52:1002-10

[37]

Ticinesi A,Cerundolo N.Gut microbiota, muscle mass and function in aging: a focus on physical frailty and sarcopenia.Nutrients2019;11:1633 PMCID:PMC6683074

[38]

Sommer F,Bharti R,Rosenstiel P.The resilience of the intestinal microbiota influences health and disease.Nat Rev Microbiol2017;15:630-8

[39]

Biagi E,Rampelli S.Gut microbiota and extreme longevity.Curr Biol2016;26:1480-5

[40]

Clegg A,Iliffe S,Rockwood K.Frailty in elderly people.Lancet2013;381:752-62 PMCID:PMC4098658

[41]

Yarnall AJ,Clegg A,Parker S.New horizons in multimorbidity in older adults.Age Ageing2017;46:882-8 PMCID:PMC5860018

[42]

Zhang XM,Xie XH.The association between frailty and delirium among hospitalized patients: an updated meta-analysis.J Am Med Dir Assoc2021;22:527-34

[43]

Mazzola P,Di Santo S.The relationship between frailty and delirium: insights from the 2017 Delirium Day study.Age Ageing2021;50:1593-9

[44]

Dani M,Jackson TA,Sampson EL.Delirium, frailty, and mortality: interactions in a prospective study of hospitalized older people.J Gerontol A Biol Sci Med Sci2018;73:415-8

[45]

Bellelli G,Panina-Bordignon P.Is delirium the cognitive harbinger of frailty in older adults? A review about the existing evidence.Front Med2017;4:188 PMCID:PMC5682301

[46]

Verdi S,Beaumont M.An investigation into physical frailty as a link between the gut microbiome and cognitive health.Front Aging Neurosci2018;10:398 PMCID:PMC6288358

[47]

Haran JP,Dutta P,McCormick B.The nursing home elder microbiome stability and associations with age, frailty, nutrition and physical location.J Med Microbiol2018;67:40-51 PMCID:PMC5884962

[48]

Haran JP,Ward DV,Bucci V.The nursing home older adult gut microbiome composition shows time-dependent dysbiosis and is influenced by medication exposures, age, environment, and frailty.J Gerontol A Biol Sci Med Sci2021;76:1930-8 PMCID:PMC8514073

[49]

Ghosh TS,Jeffery IB.Mediterranean diet intervention alters the gut microbiome in older people reducing frailty and improving health status: the NU-AGE 1-year dietary intervention across five European countries.Gut2020;69:1218-28 PMCID:PMC7306987

[50]

Jackson MA,Beaumont M.Signatures of early frailty in the gut microbiota.Genome Med2016;8:8 PMCID:PMC4731918

[51]

Ticinesi A,Tagliaferri S.The gut-muscle axis in older subjects with low muscle mass and performance: a proof of concept study exploring fecal microbiota composition and function with shotgun metagenomics sequencing.Int J Mol Sci2020;21:8946 PMCID:PMC7728056

[52]

Xu Y,Li H.Altered fecal microbiota composition in older adults with frailty.Front Cell Infect Microbiol2021;11:696186 PMCID:PMC8415883

[53]

Picca A,Calvani R.Gut microbial, inflammatory and metabolic signatures in older people with physical frailty and sarcopenia: results from the BIOSPHERE study.Nutrients2019;12:65 PMCID:PMC7019826

[54]

Maffei VJ,Blanchard E 4th.Biological aging and the human gut microbiota.J Gerontol A Biol Sci Med Sci2017;72:1474-82 PMCID:PMC5861892

[55]

Castro-Mejía JL,Krych Ł.Physical fitness in community-dwelling older adults is linked to dietary intake, gut microbiota, and metabolomic signatures.Aging Cell2020;19:e13105 PMCID:PMC7059135

[56]

Fong TG,Growdon ME,Inouye S.The interface between delirium and dementia in elderly adults.Lancet Neurol2015;14:823-32 PMCID:PMC4535349

[57]

Fong TG.The inter-relationship between delirium and dementia: the importance of delirium prevention.Nat Rev Neurol2022;18:579-96 PMCID:PMC9415264

[58]

Morandi A.Delirium superimposed on dementia.Eur Geriatr Med2020;11:53-62

[59]

Sprung J,Knopman DS.Perioperative delirium and mild cognitive impairment.Mayo Clin Proc2016;91:273-4 PMCID:PMC4961244

[60]

Kazmierski J,Latek J.Mild cognitive impairment with associated inflammatory and cortisol alterations as independent risk factor for postoperative delirium.Dement Geriatr Cogn Disord2014;38:65-78

[61]

Ticinesi A,Nouvenne A,Lauretani F.Gut microbiota, cognitive frailty and dementia in older individuals: a systematic review.Clin Interv Aging2018;13:1497-511 PMCID:PMC6120508

[62]

Jiang C,Huang P,Zhao B.The gut microbiota and alzheimer’s disease.J Alzheimers Dis2017;58:1-15

[63]

Ticinesi A,Carnevali L,Meschi T.Interaction between diet and microbiota in the pathophysiology of Alzheimer’s disease: focus on polyphenols and dietary fibers.J Alzheimers Dis2022;86:961-982

[64]

Strasser B.Intestinal microbiome in normal ageing, frailty and cognition decline.Curr Opin Clin Nutr Metab Care2023;26:8-16

[65]

Duan M,Fu H,Wang T.Preoperative microbiomes and intestinal barrier function can differentiate prodromal Alzheimer’s disease from normal neurocognition in elderly patients scheduled to undergo orthopedic surgery.Front Cell Infect Microbiol2021;11:592842 PMCID:PMC8044800

[66]

Sheng C,He B,Cai Y.Combination of gut microbiota and plasma amyloid-β as a potential index for identifying preclinical Alzheimer’s disease: a cross-sectional analysis from the SILCODE study.Alzheimers Res Ther2022;14:35 PMCID:PMC8843023

[67]

Verhaar BJH,de Leeuw FA.Gut microbiota composition is related to AD pathology.Front Immunol2021;12:794519 PMCID:PMC8843078

[68]

Xi J,Zhu H.Disturbed microbial ecology in Alzheimer’s disease: evidence from the gut microbiota and fecal metabolome.BMC Microbiol2021;21:226 PMCID:PMC8361629

[69]

Yıldırım S,Bayraktar A.Stratification of the gut microbiota composition landscape across the alzheimer's disease continuum in a turkish cohort.mSystems2022;7:e0000422 PMCID:PMC8823292

[70]

Zhou Y,Quan M,Jia J.Gut microbiota changes and their correlation with cognitive and neuropsychiatric symptoms in Alzheimer’s disease.J Alzheimers Dis2021;81:583-95

[71]

Jeong S,Tsai MJ.Cognitive function associated with gut microbial abundance in sucrose and S-Adenosyl-L-Methionine (SAMe) metabolic pathways.J Alzheimers Dis2022;87:1115-30

[72]

Cirstea MS,MacLellan AD.The oral and fecal microbiota in a canadian cohort of alzheimer’s disease.J Alzheimers Dis2022;87:247-58

[73]

Sheng C,Lin H,Han Y.Altered Gut Microbiota in Adults with Subjective Cognitive Decline: The SILCODE Study.J Alzheimers Dis2021;82:513-26

[74]

Guo M,Huang X,Huang F.Gut microbiome features of Chinese patients newly diagnosed with Alzheimer’s disease or mild cognitive impairment.J Alzheimers Dis2021;80:299-310

[75]

Zhu Z,Wu J.Altered gut microbiota and its clinical relevance in mild cognitive impairment and Alzheimer’s disease: Shanghai aging study and Shanghai memory study.Nutrients2022;14:3959 PMCID:PMC9570603

[76]

Kaiyrlykyzy A,Babenko D.Study of gut microbiota alterations in Alzheimer’s dementia patients from Kazakhstan.Sci Rep2022;12:15115 PMCID:PMC9448737

[77]

Ueda A,Shiroma H.Identification of Faecalibacterium prausnitzii strains for gut microbiome-based intervention in Alzheimer’s-type dementia.Cell Rep Med2021;2:100398 PMCID:PMC8484692

[78]

Nelson S,Catalano G,Kozel FA.Depressive symptoms before, during, and after delirium: a literature review.Psychosomatics2016;57:131-41

[79]

Simpson CA,Eliby D,Simmons JG.The gut microbiota in anxiety and depression - A systematic review.Clin Psychol Rev2021;83:101943

[80]

Mayneris-Perxachs J,Arnoriaga-Rodríguez M.Microbiota alterations in proline metabolism impact depression.Cell Metab2022;34:681-701.e10

[81]

Kim CS,Sim M.Probiotic supplementation improves cognitive function and mood with changes in gut microbiota in community-dwelling older adults: a randomized, double-blind, placebo-controlled, multicenter trial.J Gerontol A Biol Sci Med Sci2021;76:32-40 PMCID:PMC7861012

[82]

Lee SM,Krause-Sorio B.The intestinal microbiota as a predictor for antidepressant treatment outcome in geriatric depression: a prospective pilot study.Int Psychogeriatr2022;34:33-45

[83]

Ahmed S,Sampson EL.Risk factors for incident delirium among older people in acute hospital medical units: a systematic review and meta-analysis.Age Ageing2014;43:326-33 PMCID:PMC4001175

[84]

Elie M,Primeau FJ.Delirium risk factors in elderly hospitalized patients.J Gen Intern Med1998;13:204-12 PMCID:PMC1496920

[85]

Cox NJ,Ni Lochlainn M,Roberts HC.The composition of the gut microbiome differs among community dwelling older people with good and poor appetite.J Cachexia Sarcopenia Muscle2021;12:368-77 PMCID:PMC8061352

[86]

Fluitman KS,Olofsson LE.Gut microbial characteristics in poor appetite and undernutrition: a cohort of older adults and microbiota transfer in germ-free mice.J Cachexia Sarcopenia Muscle2022;13:2188-201 PMCID:PMC9397553

[87]

Leclercq S,Cani PD.Intestinal permeability, gut-bacterial dysbiosis, and behavioral markers of alcohol-dependence severity.Proc Natl Acad Sci U S A2014;111:E4485-93 PMCID:PMC4210345

[88]

Hoel RW,Takahashi PY.Polypharmacy management in older patients.Mayo Clin Proc2021;96:242-56

[89]

Mannucci PM,Pasina L.REPOSI Collaborators (REPOSI is the acronym of REgistro POliterapie SIMISocietà Italiana di Medicina Interna)Polypharmacy in older people: lessons from 10 years of experience with the REPOSI register.Intern Emerg Med2018;13:1191-200

[90]

Jennings ELM,Gallagher P.In-hospital adverse drug reactions in older adults; prevalence, presentation and associated drugs-a systematic review and meta-analysis.Age Ageing2020;49:948-58

[91]

Hein C,Piau A,Vellas B.Impact of polypharmacy on occurrence of delirium in elderly emergency patients.J Am Med Dir Assoc2014;15:850.e11-5

[92]

Salahudeen MS,Nishtala PS.Serum anticholinergic activity and cognitive and functional adverse outcomes in older people: a systematic review and meta-analysis of the literature.PLoS One2016;11:e0151084 PMCID:PMC4801377

[93]

Lange K,Stallmach A.Effects of antibiotics on gut microbiota.Dig Dis2016;34:260-8

[94]

Imhann F,Vich Vila A.Proton pump inhibitors affect the gut microbiome.Gut2016;65:740-8 PMCID:PMC4853569

[95]

Corsonello A,Bustacchini S.Adverse events of proton pump inhibitors: potential mechanisms.Curr Drug Metab2018;19:142-54

[96]

Chen A,Li KJ.Antipsychotics and the microbiota.Curr Opin Psychiatry2020;33:225-30

[97]

Bretler T,Koren O.The effects of antipsychotic medications on microbiome and weight gain in children and adolescents.BMC Med2019;17:112 PMCID:PMC6582584

[98]

Yuan X,Wang Y.Changes in metabolism and microbiota after 24-week risperidone treatment in drug naïve, normal weight patients with first episode schizophrenia.Schizophr Res2018;201:299-306

[99]

Xu Y,Fang X.Antipsychotic-induced gastrointestinal hypomotility and the alteration in gut microbiota in patients with schizophrenia.Brain Behav Immun2022;99:119-29

[100]

Ticinesi A,Lauretani F.Gut microbiota composition is associated with polypharmacy in elderly hospitalized patients.Sci Rep2017;7:11102 PMCID:PMC5593887

[101]

Vich Vila A,Sanna S.Impact of commonly used drugs on the composition and metabolic function of the gut microbiota.Nat Commun2020;11:362 PMCID:PMC6969170

[102]

Gemikonakli G,Zhang F,Tran T.Polypharmacy with high Drug Burden Index (DBI) alters the gut microbiome overriding aging effects and is reversible with deprescribing.J Gerontol A Biol Sci Med Sci2022;online first. PMCID:PMC9951051

[103]

Ticinesi A,Nouvenne A.Gut microbiome in the elderly hospitalized patient: a marker of disease and prognosis? In Faintuch J, Faintuch S, editors. Microbiome and metabolome in diagnosis, therapy, and other strategic applications. London: London Academic Press-Elsevier; 2019. pp. 287-296.

[104]

Dickson RP.The microbiome and critical illness.Lancet Respir Med2016;4:59-72 PMCID:PMC4752077

[105]

Shimizu K,Hamasaki T.Altered gut flora are associated with septic complications and death in critically ill patients with systemic inflammatory response syndrome.Dig Dis Sci2011;56:1171-7 PMCID:PMC3059822

[106]

Shimizu K,Goto M.Altered gut flora and environment in patients with severe SIRS.J Trauma2006;60:126-33

[107]

Wozniak H,Fröhlich L.The central and biodynamic role of gut microbiota in critically ill patients.Crit Care2022;26:250 PMCID:PMC9386657

[108]

Szychowiak P,Patrier J,Ruppé É.The role of the microbiota in the management of intensive care patients.Ann Intensive Care2022;12:3 PMCID:PMC8728486

[109]

Marfil-Sánchez A,Alonso-Pernas P.An integrative understanding of the large metabolic shifts induced by antibiotics in critical illness.Gut Microbes2021;13:1993598 PMCID:PMC8604395

[110]

Kelly LS,Gharaibeh R.Stress-related changes in the gut microbiome after trauma.J Trauma Acute Care Surg2021;91:192-9 PMCID:PMC8243873

[111]

Krezalek MA,Zaborina O,Alverdy JC.The shift of an intestinal “Microbiome” to a “Pathobiome” governs the course and outcome of sepsis following surgical injury.Shock2016;45:475-82 PMCID:PMC4833524

[112]

Agudelo-Ochoa GM,Giraldo-Giraldo NA.Gut microbiota profiles in critically ill patients, potential biomarkers and risk variables for sepsis.Gut Microbes2020;12:1707610 PMCID:PMC7524144

[113]

Gaibani P,Bartoletti M.The gut microbiota of critically ill patients with COVID-19.Front Cell Infect Microbiol2021;11:670424 PMCID:PMC8276076

[114]

Haak BW,Kinsella CM.Integrative transkingdom analysis of the gut microbiome in antibiotic perturbation and critical illness.mSystems2021;6 PMCID:PMC8546997

[115]

Chernevskaya E,Klimenko N.Serum and fecal profiles of aromatic microbial metabolites reflect gut microbiota disruption in critically ill patients: a prospective observational pilot study.Crit Care2020;24:312 PMCID:PMC7278238

[116]

Ojima M,Motooka D.Gut dysbiosis associated with antibiotics and disease severity and its relation to mortality in critically ill patients.Dig Dis Sci2022;67:2420-32 PMCID:PMC8090918

[117]

Prevel R,Orieux A.Gut bacteriobiota and mycobiota are both associated with Day-28 mortality among critically ill patients.Crit Care2022;26:105 PMCID:PMC9007252

[118]

Xu R,Zhu J.Dysbiosis of the intestinal microbiota in neurocritically ill patients and the risk for death.Crit Care2019;23:195 PMCID:PMC6544929

[119]

Lamarche D,Zytaruk N.PROSPECT InvestigatorsCanadian Critical Care Trials GroupCanadian Critical Care Translational Biology GroupMicrobial dysbiosis and mortality during mechanical ventilation: a prospective observational study.Respir Res2018;19:245 PMCID:PMC6286574

[120]

Milani C,Gerritsen J.Gut microbiota composition and Clostridium difficile infection in hospitalized elderly individuals: a metagenomic study.Sci Rep2016;6:25945 PMCID:PMC4863157

[121]

Victoria M,Amparo GN.Gut microbiota alterations in critically ill older patients: a multicenter study.BMC Geriatr2022;22:373 PMCID:PMC9047279

[122]

Lederer AK,Kohnert E,Müller A.Current insights: the impact of gut microbiota on postoperative complications in visceral surgery-a narrative review.Diagnostics2021;11:2099 PMCID:PMC8625751

[123]

Sciuto A,De Palma GD.Predictive factors for anastomotic leakage after laparoscopic colorectal surgery.World J Gastroenterol2018;24:2247-60 PMCID:PMC5989239

[124]

Liu H,Xu YL.Preoperative status of gut microbiota predicts postoperative delirium in patients with gastric cancer.Front Psychiatry2022;13:852269 PMCID:PMC8929925

[125]

Lian X,Sun L.Effect of anesthesia/surgery on gut microbiota and fecal metabolites and their relationship with cognitive dysfunction.Front Syst Neurosci2021;15:655695 PMCID:PMC8416053

[126]

Zhang J,Guo GJ.Abnormal composition of gut microbiota contributes to delirium-like behaviors after abdominal surgery in mice.CNS Neurosci Ther2019;25:685-96 PMCID:PMC6515708

[127]

Liufu N,Shen S.Anesthesia and surgery induce age-dependent changes in behaviors and microbiota.Aging2020;121965-1986 PMCID:PMC7053599

[128]

ENGEL GL.Delirium, a syndrome of cerebral insufficiency.J Chronic Dis1959;9:260-77

[129]

Rosengarten B,Auch D.Microcirculatory dysfunction in the brain precedes changes in evoked potentials in endotoxin-induced sepsis syndrome in rats.Cerebrovasc Dis2007;23:140-7

[130]

Taccone FS,Pierrakos C.Cerebral microcirculation is impaired during sepsis: an experimental study.Crit Care2010;14:R140 PMCID:PMC2945121

[131]

Yokota H,Kurokawa A.Regional cerebral blood flow in delirium patients.Psychiatry Clin Neurosci2003;57:337-9

[132]

Wood MD,Wood N.The use of near-infrared spectroscopy and/or transcranial doppler as non-invasive markers of cerebral perfusion in adult sepsis patients with delirium: a systematic review.J Intensive Care Med2022;37:408-22 PMCID:PMC8772019

[133]

Lu Y,Ye J.Surgery/Anesthesia disturbs mitochondrial fission/fusion dynamics in the brain of aged mice with postoperative delirium.Aging2020;12844-865 PMCID:PMC6977661

[134]

Liu Y,Yang Y.Mitochondrial DNA methylation drift and postoperative delirium in mice.Eur J Anaesthesiol2022;39:133-44

[135]

Polito A,Maho AL.Pattern of brain injury in the acute setting of human septic shock.Crit Care2013;17:R204 PMCID:PMC4057119

[136]

Rustia AJ,Best G.Microbial disruption in the gut promotes cerebral endothelial dysfunction.Physiol Rep2021;9e15100. PMCID:PMC8578899

[137]

Hammond TC,Frank JA.Gut microbial dysbiosis correlates with stroke severity markers in aged rats.Front Stroke2022;1:1026066 PMCID:PMC9945937

[138]

Sejling AS,Pedersen-Bjergaard U.Hypoglycemia-associated changes in the electroencephalogram in patients with type 1 diabetes and normal hypoglycemia awareness or unawareness.Diabetes2015;64:1760-9

[139]

Gugger JJ,Kaplan PW.A multimodal approach using somatosensory evoked potentials for prognostication in hypoglycemic encephalopathy.Clin Neurophysiol Pract2019;4:194-7 PMCID:PMC6921239

[140]

Sonneville R,Poujade J.Potentially modifiable factors contributing to sepsis-associated encephalopathy.Intensive Care Med2017;43:1075-84

[141]

Semmler A,Mormann F.Sepsis causes neuroinflammation and concomitant decrease of cerebral metabolism.J Neuroinflammation2008;5:38 PMCID:PMC2553764

[142]

Sweeney MD,Montagne A,Zlokovic BV.The role of brain vasculature in neurodegenerative disorders.Nat Neurosci2018;21:1318-31 PMCID:PMC6198802

[143]

Pedersen HK,Nielsen HB.MetaHIT ConsortiumHuman gut microbes impact host serum metabolome and insulin sensitivity.Nature2016;535:376-81

[144]

Vrieze A,Holleman F.Transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome.Gastroenterology2012;143:913-6.e7

[145]

Kootte RS,Salojärvi J.Improvement of insulin sensitivity after lean donor feces in metabolic syndrome is driven by baseline intestinal microbiota composition.Cell Metab2017;26:611-619.e6

[146]

de Groot P,Bakker GJ.Donor metabolic characteristics drive effects of faecal microbiota transplantation on recipient insulin sensitivity, energy expenditure and intestinal transit time.Gut2020;69:502-12 PMCID:PMC7034343

[147]

Blaak EE,Theis S.Short chain fatty acids in human gut and metabolic health.Benef Microbes2020;11:411-55

[148]

LaGamma EF,Pena Cruz F,Nankova BB.Bacteria - derived short chain fatty acids restore sympathoadrenal responsiveness to hypoglycemia after antibiotic-induced gut microbiota depletion.Neurobiol Stress2021;15:100376 PMCID:PMC8358200

[149]

Maclullich AM,Miller T,Cunningham C.Unravelling the pathophysiology of delirium: a focus on the role of aberrant stress responses.J Psychosom Res2008;65:229-38 PMCID:PMC4311661

[150]

Gool WA, van de Beek D, Eikelenboom P. Systemic infection and delirium: when cytokines and acetylcholine collide.Lancet2010;375:773-5

[151]

Vasunilashorn SM,Inouye SK.Cytokines and postoperative delirium in older patients undergoing major elective surgery.J Gerontol A Biol Sci Med Sci2015;701289-1295 PMCID:PMC4817082

[152]

Vasunilashorn SM,Inouye SK.High c-reactive protein predicts delirium incidence, duration, and feature severity after major noncardiac surgery.J Am Geriatr Soc2017;65:e109-16 PMCID:PMC5700456

[153]

Liu X,Zhu S.Inflammatory markers in postoperative delirium (POD) and cognitive dysfunction (POCD): a meta-analysis of observational studies.PLoS One2018;13:e0195659 PMCID:PMC5895053

[154]

Hoogland IC,van Westerloo DJ,van de Beek D.Systemic inflammation and microglial activation: systematic review of animal experiments.J Neuroinflammation2015;12:114 PMCID:PMC4470063

[155]

Subramaniyan S.Neuroinflammation and perioperative neurocognitive disorders.Anesth Analg2019;128:781-8 PMCID:PMC6437083

[156]

Cunningham C,Campion S,Perry VH.Central and systemic endotoxin challenges exacerbate the local inflammatory response and increase neuronal death during chronic neurodegeneration.J Neurosci2005;25:9275-84 PMCID:PMC6725757

[157]

Liu X,McKim DB.Cell-type-specific interleukin 1 receptor 1 signaling in the brain regulates distinct neuroimmune activities.Immunity2019;50:317-333.e6 PMCID:PMC6759085

[158]

Serantes R,Figueroa M.Interleukin-1beta enhances GABAA receptor cell-surface expression by a phosphatidylinositol 3-kinase/Akt pathway: relevance to sepsis-associated encephalopathy.J Biol Chem2006;281:14632-43

[159]

Varatharaj A.The blood-brain barrier in systemic inflammation.Brain Behav Immun2017;60:1-12

[160]

Carloni S,Mancinelli S.Identification of a choroid plexus vascular barrier closing during intestinal inflammation.Science2021;374:439-48

[161]

Carloni S.Unveiling the gut-brain axis: structural and functional analogies between the gut and the choroid plexus vascular and immune barriers.Semin Immunopathol2022;44:869-82 PMCID:PMC9301898

[162]

Bowman GL,Kirkland R.Blood-brain barrier breakdown, neuroinflammation, and cognitive decline in older adults.Alzheimers Dement2018;14:1640-50

[163]

Bairamian D,Rolhion N.Microbiota in neuroinflammation and synaptic dysfunction: a focus on Alzheimer’s disease.Mol Neurodegener2022;17:19 PMCID:PMC8898063

[164]

Heneka MT,El Khoury J.Neuroinflammation in Alzheimer’s disease.Lancet Neurol2015;14:388-405 PMCID:PMC5909703

[165]

Yadav P,Panday H.Implications of microorganisms in Alzheimer’s disease.Curr Issues Mol Biol2022;44:4584-615 PMCID:PMC9600878

[166]

Zhou R,Cho WCS.Microbiota-microglia connections in age-related cognition decline.Aging Cell2022;21:e13599 PMCID:PMC9124309

[167]

Dabrowski W,Gasinska-Blotniak M.Pathomechanisms of non-traumatic acute brain injury in critically ill patients.Medicina2020;56:469 PMCID:PMC7560040

[168]

Tilg H,Adolph TE.The intestinal microbiota fuelling metabolic inflammation.Nat Rev Immunol2020;20:40-54

[169]

Mou Y,Zhou L.Gut microbiota interact with the brain through systemic chronic inflammation: implications on neuroinflammation, neurodegeneration, and aging.Front Immunol2022;13:796288 PMCID:PMC9021448

[170]

Candelli M,Pignataro G.Interaction between lipopolysaccharide and gut microbiota in inflammatory bowel diseases.Int J Mol Sci2021;22:6242 PMCID:PMC8226948

[171]

Patterson GT,Peniche A.Pathologic inflammation in malnutrition is driven by proinflammatory intestinal microbiota, large intestine barrier dysfunction, and translocation of bacterial lipopolysaccharide.Front Immunol2022;13:846155 PMCID:PMC9204284

[172]

Zhou X,Guo J.Gut-dependent microbial translocation induces inflammation and cardiovascular events after ST-elevation myocardial infarction.Microbiome2018;6:66 PMCID:PMC5883284

[173]

Buford TW,VanDerPol WJ.Composition and richness of the serum microbiome differ by age and link to systemic inflammation.Geroscience2018;40:257-68 PMCID:PMC6060185

[174]

Koh A,Kovatcheva-Datchary P.From dietary fiber to host physiology: short-chain fatty acids as key bacterial metabolites.Cell2016;165:1332-45

[175]

Agus A,Sokol H.Gut microbiota regulation of tryptophan metabolism in health and disease.Cell Host Microbe2018;23:716-24

[176]

Alexeev EE,Kao DJ.Microbiota-derived indole metabolites promote human and murine intestinal homeostasis through regulation of interleukin-10 receptor.Am J Pathol2018;188:1183-94 PMCID:PMC5906738

[177]

Dodd D,Van Treuren W.A gut bacterial pathway metabolizes aromatic amino acids into nine circulating metabolites.Nature2017;551:648-52 PMCID:PMC5850949

[178]

Lee JH.Indole as an intercellular signal in microbial communities.FEMS Microbiol Rev2010;34:426-44

[179]

Kumar A.Indole signaling at the host-microbiota-pathogen interface.mBio2019;10 PMCID:PMC6550529

[180]

Hou Q,Liu H.Lactobacillus accelerates ISCs regeneration to protect the integrity of intestinal mucosa through activation of STAT3 signaling pathway induced by LPLs secretion of IL-22.Cell Death Differ2018;25:1657-70 PMCID:PMC6143595

[181]

Scott SA,Chang PV.Microbial tryptophan metabolites regulate gut barrier function via the aryl hydrocarbon receptor.Proc Natl Acad Sci USA2020;117(32)19376-19387 PMCID:PMC7431026

[182]

Ihekweazu FD,Ruan W.Bacteroides ovatus promotes IL-22 production and reduces trinitrobenzene sulfonic acid-driven colonic inflammation.Am J Pathol2021;191:704-19 PMCID:PMC8027925

[183]

Horvath TD,Haidacher SJ.Bacteroides ovatus colonization influences the abundance of intestinal short chain fatty acids and neurotransmitters.iScience2022;25:104158 PMCID:PMC9038548

[184]

Schirmer M,Vlamakis H.Linking the human gut microbiome to inflammatory cytokine production capacity.Cell2016;167:1125-1136.e8 PMCID:PMC5131922

[185]

Cervenka I,Ruas JL.Kynurenines: Tryptophan’s metabolites in exercise, inflammation, and mental health.Science2017;357:eaaf9794

[186]

Kennedy PJ,Dinan TG.Kynurenine pathway metabolism and the microbiota-gut-brain axis.Neuropharmacology2017;112:399-412

[187]

Kim YK.Neuroinflammation and the immune-kynurenine pathway in anxiety disorders.Curr Neuropharmacol2018;16:574-82 PMCID:PMC5997870

[188]

Stone TW,Mackay GM,Darlington LG.Tryptophan, adenosine, neurodegeneration and neuroprotection.Metab Brain Dis2007;22:337-52

[189]

Vohra M,Lin L.Kynurenic acid accumulation underlies learning and memory impairment associated with aging.Genes Dev2018;32:14-9 PMCID:PMC5828390

[190]

Kozak R,Strick CA.Reduction of brain kynurenic acid improves cognitive function.J Neurosci2014;34:10592-602 PMCID:PMC6802596

[191]

Gulaj E,Bien B.Kynurenine and its metabolites in Alzheimer’s disease patients.Adv Med Sci2010;55:204-11

[192]

Solvang SH,Aarsland D.Kynurenines, neuropsychiatric symptoms, and cognitive prognosis in patients with mild dementia.Int J Tryptophan Res2019;12:1178646919877883 PMCID:PMC6769202

[193]

Voils SA,Singh S,Garrett TJ.Intensive care unit delirium in surgical patients is associated with upregulation in tryptophan metabolism.Pharmacotherapy2020;40:500-6

[194]

Yano JM,Donaldson GP.Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis.Cell2015;161:264-76 PMCID:PMC4393509

[195]

Reigstad CS,Rainey JF 3rd.Gut microbes promote colonic serotonin production through an effect of short-chain fatty acids on enterochromaffin cells.FASEB J2015;29:1395-403 PMCID:PMC4396604

[196]

Chang-Graham AL,Engevik MA.Human intestinal enteroids with inducible neurogenin-3 expression as a novel model of gut hormone secretion.Cell Mol Gastroenterol Hepatol2019;8:209-29

[197]

Tsuruta T,Osaki Y,Aoki-Yoshida A.Organoids as an ex vivo model for studying the serotonin system in the murine small intestine and colon epithelium.Biochem Biophys Res Commun2016;474:161-7

[198]

Lund ML,Engelstoft MS.Enterochromaffin 5-HT cells - A major target for GLP-1 and gut microbial metabolites.Mol Metab2018;11:70-83 PMCID:PMC6001397

[199]

Akiba Y,Kaji I.Short-chain fatty acid sensing in rat duodenum.J Physiol2015;593:585-99 PMCID:PMC4324707

[200]

Akiba Y,Narimatsu K.FFA2 activation combined with ulcerogenic COX inhibition induces duodenal mucosal injury via the 5-HT pathway in rats.Am J Physiol Gastrointest Liver Physiol2017;313:G117-28 PMCID:PMC5582879

[201]

Luck B,Engevik KA.Neurotransmitter profiles are altered in the gut and brain of mice mono-associated with Bifidobacterium dentium.Biomolecules2021;11:1091 PMCID:PMC8392031

[202]

Engevik MA,Visuthranukul C.Human-derived Bifidobacterium dentium Modulates the mammalian serotonergic system and gut-brain axis.Cell Mol Gastroenterol Hepatol2021;11:221-48 PMCID:PMC7683275

[203]

Nzakizwanayo J,Standen G,Patel BA.Escherichia coli Nissle 1917 enhances bioavailability of serotonin in gut tissues through modulation of synthesis and clearance.Sci Rep2015;5:17324 PMCID:PMC4663480

[204]

Nakaita Y,Shigyo T.Heat-killed Lactobacillus brevis SBC8803 induces serotonin release from intestinal cells.FNS2013;04:767-71

[205]

Williams BB,Cimermancic P.Discovery and characterization of gut microbiota decarboxylases that can produce the neurotransmitter tryptamine.Cell Host Microbe2014;16:495-503 PMCID:PMC4260654

[206]

Robinson TN,Angles EM.Low tryptophan levels are associated with postoperative delirium in the elderly.Am J Surg2008;196:670-4 PMCID:PMC2586980

[207]

Pandharipande PP,Adams JR.Plasma tryptophan and tyrosine levels are independent risk factors for delirium in critically ill patients.Intensive Care Med2009;35:1886-92 PMCID:PMC3673700

[208]

Marcantonio ER,Culley D,Alsop D.Serum biomarkers for delirium.J Gerontol A Biol Sci Med Sci2006;611281-1286

[209]

Maldonado JR.Neuropathogenesis of delirium: review of current etiologic theories and common pathways.Am J Geriatr Psychiatry2013;211190-1222

[210]

Zhang J,Guo G.Anesthesia and surgery induce delirium-like behavior in susceptible mice: the role of oxidative stress.Am J Transl Res2018;102435-2444. PMCID:PMC6129548

[211]

Kaźmierski J,Pawlak A.Oxidative stress and soluble receptor for advanced glycation end-products play a role in the pathophysiology of delirium after cardiac surgery.Sci Rep2021;11:23646 PMCID:PMC8655063

[212]

Lopez MG,DeMatteo A.Intraoperative oxidative damage and delirium after cardiac surgery.Anesthesiology2020;132:551-61 PMCID:PMC7015795

[213]

Pang Y,Zhang Y.Effects of inflammation and oxidative stress on postoperative delirium in cardiac surgery.Front Cardiovasc Med2022;9:1049600 PMCID:PMC9731159

[214]

Egberts A,Wijnbeld EH.Disturbed serotonergic neurotransmission and oxidative stress in elderly patients with delirium.Dement Geriatr Cogn Dis Extra2015;5:450-8 PMCID:PMC4777943

[215]

Dumitrescu L,Cozma L.Oxidative stress and the microbiota-gut-brain axis.Oxid Med Cell Longev2018;20182406594 PMCID:PMC6304899

[216]

Mossad O,Yilmaz B.Gut microbiota drives age-related oxidative stress and mitochondrial damage in microglia via the metabolite N6-carboxymethyllysine.Nat Neurosci2022;25295-305

[217]

Lin WY,Kuo YW,Ho HH.Probiotics and their metabolites reduce oxidative stress in middle-aged mice.Curr Microbiol2022;79:104 PMCID:PMC8843923

[218]

Finamore A,Nobili F,Raguzzini A.Redox role of lactobacillus casei shirota against the cellular damage induced by 2,2'-Azobis (2-amidinopropane) dihydrochloride-induced oxidative and inflammatory stress in enterocytes-like epithelial cells.Front Immunol2018;9:1131 PMCID:PMC5976738

[219]

Wang Y,Xie J.Protective effects of probiotic Lactobacillus casei Zhang against endotoxin- and d-galactosamine-induced liver injury in rats via anti-oxidative and anti-inflammatory capacities.Int Immunopharmacol2013;15:30-7

[220]

Engevik MA,Ruan W.Bifidobacterium dentium-derived y-glutamylcysteine suppresses ER-mediated goblet cell stress and reduces TNBS-driven colonic inflammation.Gut Microbes2021;13:1-21 PMCID:PMC8128206

[221]

Vitheejongjaroen P,Puttarat N,Taweechotipatr M.Bifidobacterium animalis MSMC83 improves oxidative stress and gut microbiota in D-galactose-induced rats.Antioxidants2022;11:2146 PMCID:PMC9686799

[222]

Ejtahed HS,Homayouni-Rad A,Asghari-Jafarabadi M.Probiotic yogurt improves antioxidant status in type 2 diabetic patients.Nutrition2012;28:539-43

[223]

Shandilya S,Kumar Jha N,Ruokolainen J.Interplay of gut microbiota and oxidative stress: perspective on neurodegeneration and neuroprotection.J Adv Res2022;38:223-44 PMCID:PMC9091761

[224]

Weiss GA.Mechanisms and consequences of intestinal dysbiosis.Cell Mol Life Sci2017;74:2959-77

[225]

Liu L,Jin D,Long B.General anesthesia bullies the gut: a toxic relationship with dysbiosis and cognitive dysfunction.Psychopharmacology2022;239:709-28

[226]

Xu X,Yan E,Liu C.Perioperative neurocognitive dysfunction: thinking from the gut?.Aging2020;1215979-15817 PMCID:PMC7467368

[227]

Lu J,Gao S,Zong Y.The role of gut microbiota-gut-brain axis in perioperative neurocognitive dysfunction.Front Pharmacol2022;13:879745 PMCID:PMC9237434

[228]

Woo V.Epigenetic regulation by gut microbiota.Gut Microbes2022;14:2022407 PMCID:PMC8744890

[229]

Rossi M,Raimondi S.Folate production by probiotic bacteria.Nutrients2011;3:118-34 PMCID:PMC3257725

[230]

Ansari I,Gutekunst J.The microbiota programs DNA methylation to control intestinal homeostasis and inflammation.Nat Microbiol2020;5:610-9

[231]

Röth D,Hu W.Two-carbon folate cycle of commensal Lactobacillus reuteri 6475 gives rise to immunomodulatory ethionine, a source for histone ethylation.FASEB J2019;33:3536-48 PMCID:PMC6404577

[232]

Krautkramer KA,Romano KA.Diet-microbiota interactions mediate global epigenetic programming in multiple host tissues.Mol Cell2016;64:982-92 PMCID:PMC5227652

[233]

Alenghat T,Saenz SA.Histone deacetylase 3 coordinates commensal-bacteria-dependent intestinal homeostasis.Nature2013;504:153-7 PMCID:PMC3949438

[234]

Fellows R,Stellato C.Microbiota derived short chain fatty acids promote histone crotonylation in the colon through histone deacetylases.Nat Commun2018;9:105 PMCID:PMC5760624

[235]

der Hee B, Wells JM. Microbial regulation of host physiology by short-chain fatty acids.Trends Microbiol2021;29:700-12

[236]

Evans LW,Ferguson BS.Dietary natural products as epigenetic modifiers in aging-associated inflammation and disease.Nat Prod Rep2020;37:653-76 PMCID:PMC7577396

[237]

Liang L,Qian J,Xu J.Long noncoding RNA expression profiles in gut tissues constitute molecular signatures that reflect the types of microbes.Sci Rep2015;5:11763 PMCID:PMC4485256

[238]

Wahba NE,Marra PS.Genome-wide DNA methylation analysis of post-operative delirium with brain, blood, saliva, and buccal samples from neurosurgery patients.J Psychiatr Res2022;156:245-51

[239]

Yamanashi T,Wahba NE.The genome-wide DNA methylation profiles among neurosurgery patients with and without post-operative delirium.Psychiatry Clin Neurosci2023;77:48-55 PMCID:PMC9812874

[240]

Sadahiro R,James F.Major surgery induces acute changes in measured DNA methylation associated with immune response pathways.Sci Rep2020;10:5743 PMCID:PMC7113299

[241]

Shinozaki G,Hing BWQ.Epigenetics of delirium and aging: potential role of dna methylation change on cytokine genes in glia and blood along with aging.Front Aging Neurosci2018;10:311 PMCID:PMC6206747

[242]

Stilling RM,Cryan JF.Microbial genes, brain & behaviour - epigenetic regulation of the gut-brain axis.Genes Brain Behav2014;13:69-86

[243]

Yang XD,Wu HY.Effects of prebiotic galacto-oligosaccharide on postoperative cognitive dysfunction and neuroinflammation through targeting of the gut-brain axis.BMC Anesthesiol2018;18:177 PMCID:PMC6267821

[244]

Jiang XL,Zhou XX.Intestinal dysbacteriosis mediates the reference memory deficit induced by anaesthesia/surgery in aged mice.Brain Behav Immun2019;80:605-15

[245]

Wen J,Wang L.Gut microbiome improves postoperative cognitive function by decreasing permeability of the blood-brain barrier in aged mice.Brain Res Bull2020;164:249-56

[246]

Yang L,Dong Y.Electroacupuncture attenuates surgical pain-induced delirium-like behavior in mice via remodeling gut microbiota and dendritic spine.Front Immunol2022;13:955581 PMCID:PMC9393710

[247]

Maekawa M,Yahagi M.Association between postoperative changes in the gut microbiota and pseudopsia after cardiac surgery: prospective observational study.BMC Surg2020;20:247 PMCID:PMC7576870

[248]

Yang Z,Qian X,Wang Y.Mechanical bowel preparation is a risk factor for postoperative delirium as it alters the gut microbiota composition: a prospective randomized single-center study.Front Aging Neurosci2022;14:847610 PMCID:PMC9014128

[249]

Gotoh K,Kato H.Fecal microbiota transplantation as therapy for recurrent Clostridioides difficile infection is associated with amelioration of delirium and accompanied by changes in fecal microbiota and the metabolome.Anaerobe2022;73:102502

[250]

Yu H,Yang M.A large-scale causal analysis of gut microbiota and delirium: A Mendelian randomization study.J Affect Disord2023;329:64-71

[251]

Xie Z,Baldyga K.The association between gut microbiota and postoperative delirium in patients.Res Sq2023;rs.3.rs-2456664 PMCID:PMC9900981

[252]

Sugita S,Kinjo S.The effects of microbiome-targeted therapy on cognitive impairment and postoperative cognitive dysfunction-a systematic review.PLoS One2023;18:e0281049 PMCID:PMC9904456

[253]

Melrose J.The potential of flavonoids and flavonoid metabolites in the treatment of neurodegenerative pathology in disorders of cognitive decline.Antioxidants2023;12:663 PMCID:PMC10045397

[254]

Melrose J.Natural and semi-synthetic flavonoid anti-SARS-CoV-2 agents for the treatment of long COVID-19 disease and neurodegenerative disorders of cognitive decline.Front Biosci2022;14(4)27

[255]

Lin X,Dong R,Bi YL.Habitual tea consumption and postoperative delirium after total hip/knee arthroplasty in elderly patients: the PNDABLE study.Brain Behav2022;12:e2612 PMCID:PMC9226797

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