Abstract
Frailty, which is a syndrome that encompasses losses in physical, psychological and
social domains, is responsible for enhanced vulnerability to endogenous and/or exogenous
stressors. Frailty is a public health problem for an ageing society; however, it is
poorly understood and often under-recognised in clinical settings. In particular,
the impact of frailty on either intestinal functions, i.e. immune response, permeability,
and absorption, or gut microbiota composition is as yet mostly unexplored. A better
comprehension of the intestinal dysfunction occurring in the elderly would help in
clarifying the mechanisms predisposing frail patients to a higher risk of infectious
or inflammatory events. Moreover, recent evidence suggests that senescence-induced
perturbations of the gut–brain axis are involved in the neuroinflammation process,
thus raising the hypothesis that preserving gut permeability and preventing frailty-related
changes in the microbiota composition might reduce the susceptibility to develop neurodegenerative
disorders. In this review, we highlight the current insights concerning the relationship
between frailty, intestinal functions, microbiota, and gut–brain axis.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Digestive and Liver DiseaseAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Frailty in elderly people.Lancet. 2013; 381: 752-762
- Frailty in older adults: evidence for a phenotype.J Gerontol A Biol Sci Med Sci. 2001; 56: M146-M156
- Frailty consensus: a call to action.J Am Med Dir Assoc. 2013; 14: 392-397
- Frailty syndrome: a transitional state in a dynamic process.Gerontology. 2009; 55: 539-549
- Frailty measurement in research and clinical practice: a review.Eur J Intern Med. 2016; 31: 3-10
- Intestinal epithelial cells: regulators of barrier function and immune homeostasis.Nat Rev Immunol. 2014; 14: 141-153
- Inflamm-aging. An evolutionary perspective on immunosenescence.Ann N Y Acad Sci. 2000; 908: 244-254
- Inflamm-ageing.Curr Opin Clin Nutr Metab Care. 2013; 16: 14-20
- Intestinal permeability defects: is it time to treat.Clin Gastroenterol Hepatol. 2013; 11: 1075-1083
- Gut microbiota composition correlates with diet and health in the elderly.Nature. 2012; 488: 178-184
- The comprehensive geriatric assessment and the multidimensional approach. A new look at the older patient with gastroenterologic disorders.Best Pract Res Clin Gastroenterol. 2009; 23: 829-837
- Development and validation of a multidimensional prognostic index for one-year mortality from comprehensive geriatric assessment in hospitalized older patients.Rejuvenation Res. 2008; 11: 151-161
- A standard procedure for creating a frailty index.BMC Geriatr. 2008; 8: 24
- A simple frailty questionnaire (FRAIL) predicts outcomes in middle aged frican Americans.J Nutr Health Aging. 2012; 16: 601-608
- Comparing the prognostic accuracy for all-cause mortality of frailty instruments: a multicentre 1 year follow up in hospitalized oled patients.PLoS One. 2012; 7e29090
- Transitions between frailty states among community living older persons.Arch Intern Med. 2006; 166: 418-423
- Untangling the concepts of disability, frailty and comorbidity: implication for improved targeting and care.J Gerontol A Biol Sci Med Sci. 2004; 59: 255-263
- The relationship of multimorbidity with disability and frailty in the oldest patients: a cross-sectional analysis of three measures of multimorbidity in the BELFRAIL cohort.Eur J Gen Pract. 2015; 21: 39-44
- Frailty and activation of inflammation and coagulation system with and without clinical comorbidities: results from the cardiovascular health study.Arch Intern Med. 2002; 162: 2333-2341
- Inflammatory mediators in the elderly.Exp Gerontol. 2004; 39: 687-699
- Age-related inflammatory cytokines and disease.Immunol Allergy Clin North Am. 2003; 23: 15-39
- Serum cytokine profiles in healthy young and elderly population assessed using multiplexed bead-based immunoassays.J Transl Med. 2011; 9: 113
- Inflamm-aging does not simply reflect increases in pro-inflammatory markers.Mech Ageing Dev. 2014; 139: 49-57
- Inflammaging and anti-inflammaging: a systemic perspective on aging and longevity emerged from studies in humans.Mech Ageing Dev. 2007; 128: 92-105
- Age-associated remodeling of the intestinal epithelial barrier.J Gerontol A Biol Sci Med Sci. 2013; 68: 1045-1056
- Age-associated modifications of intestinal permeability and innate immunity in human small intestine.Clin Sci (Lond). 2015; 129: 515-527
- Aging and the mucosal immune system in the intestine.Biogerontology. 2015; 16: 133-145
- The functional maturation of M cells is dramatically reduced in the Peyer’s patches of aged mice.Mucosal Immunol. 2013; 6: 1027-1037
- Aging correlates with reduction in regulatory-type cytokines and T cells in the gut mucosa.Immunobiology. 2011; 216: 1085-1093
- Mucosal immunity and tolerance in the elderly.Mech Ageing Dev. 2004; 125: 889-898
- The natural history of diverticulitis: fact and theory.J Clin Gastroenterol. 2004; 38: S2-7
- Risk factors for complicated diverticulitis: systematic review and meta-analysis.Int J Colorectal Dis. 2017; 32: 1375-1383
- A hypothesis: is diverticulitis a type of inflammatory bowel disease?.J Clin Gastroenterol. 2006; 40: S121-S125
- Reduced intestinal motility, mucosal barrier function, and inflammation in aged monkeys.J Nutr Health Aging. 2017; 21: 354-361
- Aging-associated increase in intestinal absorption of macromolecules.Gerontology. 1985; 31: 133-137
- Aging-associated increase in intestinal permeability to polyethylene glycol 900.Dig Dis Sci. 1987; 32: 285-288
- Ageing and small-bowel mucosa: a morphometric study.Gerontology. 1986; 32: 60-65
- Changes in small-intestine permeability with aging.J Am Geriatr Soc. 1995; 43: 160-164
- Small intestinal permeability in older adults.Physiol Rep. 2014; 2e00281
- Intestinal permeability biomarker zonulin is elevated in healthy aging.J Am Med Dir Assoc. 2017; ([Epub ahead of print].)
- Small bowel enterocyte apoptosis and proliferation are increased in the elderly.Gerontology. 2002; 48: 204-208
- Effect of age and frailty on ghrelin and cholecystokinin responses to a meal test.Am J Clin Nutr. 2009; 89: 1410-1417
- Gastrointestinal peptides, gastrointestinal motility, and anorexia of aging in frail elderly persons.Neurogastroenterol Motil. 2013; 25291-e245
- Frailty syndrome and risk of sepsis in the REasons for Geographic And Racial Differences in Stroke (REGARDS) cohort.J Intensive Care Med. 2017; ([Epub ahead of print].)
- Common features of patients with autoimmune atrophic gastritis.Clin Gastroenterol Hepatol. 2012; 10: 812-814
- Micronutrient deficiencies in patients with chronic atrophic autoimmune gastritis: a review.World J Gastroenterol. 2017; 23: 563-572
- Acute and chronic thrombosis of the mesenteric arteries associated with malabsorption; a report of two cases successfully treated by thromboendarterectomy.N Engl J Med. 1958; 258: 874-878
- Drug-induced malabsorption.Mayo Clin Proc. 1975; 50: 284-293
- Clinical consequences of polypharmacy in elderly.Expert Opin Drug Saf. 2014; 13: 57-65
- Severe spruelike enteropathy associated with olmesartan.Mayo Clin Proc. 2012; 87: 732-738
- Gut microbiota in health and disease.Physiol Rev. 2010; 90: 859-904
- Ageing of the human metaorganism: the microbial counterpart.Age (Dordr). 2012; 34: 247-267
- Age-related changes in gut microbiota composition from newborn to centenarian: a cross-sectional study.BMC Microbiol. 2016; 16: 90
- Gene expression profiling gut microbiota in different races of humans.Sci Rep. 2016; 6: 23075
- The gut microbiota of centenarians: signatures of longevity in the gut microbiota profile.Mech Ageing Dev. 2017; 165: 180-184
- Gut microbiota: a player in aging and a target for anti-aging intervention.Ageing Res Rev. 2017; 35: 36-45
- Gut microbiota and extreme longevity.Curr Biol. 2016; 26: 1480-1485
- Fecal microbiota composition and frailty.Appl Environ Microbiol. 2005; 71: 6438-6442
- Signatures of early frailty in the gut microbiota.Genome Med. 2016; 8: 8
- Association between Faecalibacterium prausnitzii reduction and inflammatory bowel disease: a meta-analysis and systematic review of the literature.Gastroenterol Res Pract. 2014; 2014: 872725
- Faecalibacterium prausnitzii and human intestinal health.Curr Opin Microbiol. 2013; 16: 255-261
- Effect of a prebiotic formulation on frailty syndrome: a randomized, double-blind clinical trial.Int J Mol Sci. 2016; 17
- Prevalence and appropriateness of drug prescriptions for peptic ulcer and gastro-esophageal reflux disease in a cohort of hospitalized elderly.Eur J Intern Med. 2011; 22: 205-210
- Multimorbidity and polypharmacy in the elderly: lessons from REPOSI.Intern Emerg Med. 2014; 9: 723-734
- Proton pump inhibitors alter the composition of the gut microbiota.Gut. 2015; 0: 1-8
- Clostridium difficile infection.N Engl J Med. 2015; 372: 1539-1548
- Antimicrobial-associated risk factors for Clostridium difficile infection.Clin Infect Dis. 2008; 46: S19-S31
- Multimorbidity in elderly hospitalised patients and risk of Clostridium difficile infection: a retrospective study with the cumulative illness rating scale (CIRS).BMJ Open. 2015; 5e009316
- Clostridium difficile diarrhea in the elderly: current issues and management options.Drugs Aging. 2015; 32: 639-647
- Risk factors for Clostridium difficile infection.J Hosp Infect. 1998; 40: 1-15
- Infectious disease outbreaks in nursing homes: an unappreciated hazard for frail elderly persons.Clin Infect Dis. 2003; 36: 870-876
- The effect of ageing with and without non-steroidal anti-inflammatory drugs on gastrointestinal microbiology and immunology.Br J Nutr. 2008; 100: 130-137
- The effect of age and non-steroidal anti-inflammatory drugs on human intestinal microbiota composition.Br J Nutr. 2010; 103: 227-234
- Efficacy of Lactobacillus casei treatment on small bowel injury in chronic low-dose aspirin users: a pilot randomized controlled study.J Gastroenterol. 2011; 46: 894-905
- Gut feelings: the emerging biology of gut–brain communication.Nat Rev Neurosci. 2011; 12: 453-466
- The role of microbiome in central nervous system disorders.Brain Behav Immun. 2014; 38: 1-12
- Brain–gut-microbiota axis in Parkinson’s disease.World J Gastroenterol. 2015; 21: 10609-10620
- Parkinson’s disease: clinical features and diagnosis.J Neurol Neurosurg Psychiatry. 2008; 79: 368-376
- Parkinson’s disease and alpha-synucleinopathies: from arising pathways to therapeutic challenge.Cent Nerv Syst Agents Med Chem. 2015; 15: 109-116
- Microbiota-gut–brain signalling in Parkinson’s disease: implications for non-motor symptoms.Parkinsonism Relat Disord. 2016; 27: 1-8
- Multi-organ distribution of phosphorylated alphasynuclein histopathology in subjects with Lewy body disorders.Acta Neuropathol. 2010; 119: 689-702
- Gastrointestinal manifestations in Parkinson’s disease: prevalence and occurrence before motor symptoms.J Neurol. 2013; 260: 1332-1338
- Faecal transplant eases symptoms of Parkinson’s disease.New Sci. 2011; 209: 8-9
- Vagotomy and subsequent risk of Parkinson’s disease.Ann Neurol. 2015; 78: 522-529
- Gut microbiota regulate motor deficits and neuroinflammation in a model of Parkinson’s disease.Cell. 2016; 167: 1469-1480
- Gut–brain and brain–gut axis in Parkinson’s disease models: effects of a uridine and fish oil diet.Nutr Neurosci. 2017; ([Epub ahead of print].)
- Colonic inflammation in Parkinson’s disease.Neurobiol Dis. 2013; 50: 42-48
- Gut microbiota are related to Parkinson’s disease and clinical phenotype.Mov Disord. 2015; 30: 350-358
- Alzheimer’s disease.Lancet. 2011; 377: 1019-1031
- Alzheimer’s disease facts and figures.Alzheimers Dement. 2016; 12: 459-509
- Bacterial infection causes stress-induced memory dysfunction in mice.Gut. 2011; 60: 307-317
- The intestinal microbiota affect central levels of brain-derived neurotropic factor and behavior in mice.Gastroenterology. 2011; 141: 599-609
- Is altered BDNF biosynthesis a general feature in patients with cognitive dysfunctions?.Neuroscientist. 2013; 19: 345-353
- Apathy and APOE4 are associated with reduced BDNF levels in Alzheimer’s disease.J Alzheimers Dis. 2014; 42: 1347-1355
- Prolonged elevation in hippocampal Aβ and cognitive deficits following repeated endotoxin exposure in the mouse.Behav Brain Res. 2012; 229: 176-184
- Antibiotic-induced perturbations in gut microbial diversity influences neuro-inflammation and amyloidosis in a murine model of Alzheimer’s disease.Sci Rep. 2016; 6: 30028
- Host microbiota constantly control maturation and function of microglia in the CNS.Nat Neurosci. 2015; 18: 965-977
- Reduction of Abeta amyloid pathology in APPPS1 transgenic mice in the absence of gut microbiota.Sci Rep. 2017; 7: 41802
- Modulation of intestinal microbiota by the probiotic VSL#3 resets brain gene expression and ameliorates the age-related deficit in LTP.PLoS One. 2014; 9
- Potentially modifiable risk factors for dementia in identical twins.Alzheimers Dement. 2006; 2: 110-117
- Tooth loss, dementia and neuropathology in the Nun study.J Am Dent Assoc. 2007; 138: 1314-1322
- Periodontal disease associates with higher brain amyloid load in normal elderly.Neurobiol Aging. 2015; 36: 627-633
- Association of brain amyloidosis with pro-inflammatory gut bacterial taxa and peripheral inflammation markers in cognitively impaired elderly.Neurobiol Aging. 2017; 49: 60-68
- Gastrointestinal microbiota and their contribution to healthy aging.Dig Dis. 2016; 34: 194-201
Article info
Publication history
Published online: March 16, 2018
Accepted:
March 8,
2018
Received:
January 9,
2018
Identification
Copyright
© 2018 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.
