Are self-reported gastrointestinal symptoms among older adults associated with increased intestinal permeability and psychological distress?
Tóm tắt
Despite the substantial number of older adults suffering from gastrointestinal (GI) symptoms little is known regarding the character of these complaints and whether they are associated with an altered intestinal barrier function and psychological distress. Our aim was to explore the relationship between self-reported gut health, intestinal permeability and psychological distress among older adults. Three study populations were included: 1) older adults with GI symptoms (n = 24), 2) a group of older adults representing the general elderly population in Sweden (n = 22) and 3) senior orienteering athletes as a potential model of healthy ageing (n = 27). Questionnaire data on gut-health, psychological distress and level of physical activity were collected. Intestinal permeability was measured by quantifying zonulin in plasma. The level of systemic and local inflammation was monitored by measuring C-reactive protein (CRP), hydrogen peroxide in plasma and calprotectin in stool samples. The relationship between biomarkers and questionnaire data in the different study populations was illustrated using a Principal Component Analysis (PCA). Older adults with GI symptoms displayed significantly higher levels of both zonulin and psychological distress than both general older adults and senior orienteering athletes. The PCA analysis revealed a separation between senior orienteering athletes and older adults with GI symptoms and showed an association between GI symptoms, psychological distress and zonulin. Older adults with GI symptoms express increased plasma levels of zonulin, which might reflect an augmented intestinal permeability. In addition, this group suffer from higher psychological distress compared to general older adults and senior orienteering athletes. This relationship was further confirmed by a PCA plot, which illustrated an association between GI symptoms, psychological distress and intestinal permeability.
Tài liệu tham khảo
Cohen JE. Human population: the next half century. Science. 2003;302(5648):1172–5.
Algilani S, Ostlund-Lagerstrom L, Kihlgren A, Blomberg K, Brummer RJ, Schoultz I. Exploring the concept of optimal functionality in old age. J Multidiscip Healthc. 2014;7:69–79.
Bosshard W, Dreher R, Schnegg JF, Bula CJ. The treatment of chronic constipation in elderly people: an update. Drugs Aging. 2004;21(14):911–30.
Kinnunen O. Study of constipation in a geriatric hospital, day hospital, old people's home and at home. Aging (Milano). 1991;3(2):161–70.
Scallan E, Majowicz SE, Hall G, Banerjee A, Bowman CL, Daly L, Jones T, Kirk MD, Fitzgerald M, Angulo FJ. Prevalence of diarrhoea in the community in Australia, Canada, Ireland, and the United States. Int J Epidemiol. 2005;34(2):454–60.
Talley NJ, O'Keefe EA, Zinsmeister AR, Melton LJ. 3rd: prevalence of gastrointestinal symptoms in the elderly: a population-based study. Gastroenterology. 1992;102(3):895–901.
Pilotto A, Franceschi M, Vitale D, Zaninelli A, Di Mario F, Seripa D, Rengo F, Firi, Investigators SP. The prevalence of diarrhea and its association with drug use in elderly outpatients: a multicenter study. Am J Gastroenterol. 2008;103(11):2816–23.
Eckerblad J, Theander K, Ekdahl A, Unosson M, Wirehn AB, Milberg A, Krevers B, Jaarsma T. Symptom burden in community-dwelling older people with multimorbidity: a cross-sectional study. BMC Geriatr. 2015;15:1.
James I, Blomberg K, Kihlgren A. A meaningful daily life in nursing homes - a place of shelter and a space of freedom: a participatory appreciative action reflection study. BMC Nurs. 2014;13:19.
Ostlund-Lagerstrom L, Blomberg K, Algilani S, Schoultz M, Kihlgren A, Brummer RJ, Schoultz I. Senior orienteering athletes as a model of healthy aging: a mixed-method approach. BMC Geriatr. 2015;15:76.
Gareau MG. Microbiota-gut-brain axis and cognitive function. Adv Exp Med Biol. 2014;817:357–71.
Bednarska O, Walter SA, Casado-Bedmar M, Strom M, Salvo-Romero E, Vicario M, Mayer EA, Keita AV. Vasoactive intestinal polypeptide and mast cells regulate increased passage of colonic Bacteria in patients with irritable bowel syndrome. Gastroenterology. 2017;153(4):948–60. e943
Salim SY, Soderholm JD. Importance of disrupted intestinal barrier in inflammatory bowel diseases. Inflamm Bowel Dis. 2011;17(1):362–81.
Vancamelbeke M, Vermeire S. The intestinal barrier: a fundamental role in health and disease. Expert Rev Gastroenterol Hepatol. 2017;11(9):821–34.
Bischoff SC, Barbara G, Buurman W, Ockhuizen T, Schulzke JD, Serino M, Tilg H, Watson A, Wells JM. Intestinal permeability--a new target for disease prevention and therapy. BMC Gastroenterol. 2014;14:189.
Wells JM, Brummer RJ, Derrien M, MacDonald TT, Troost F, Cani PD, Theodorou V, Dekker J, Meheust A, de Vos WM, et al. Homeostasis of the gut barrier and potential biomarkers. Am J Physiol Gastrointest Liver Physiol. 2017;312(3):G171–93.
Suzuki T. Regulation of intestinal epithelial permeability by tight junctions. Cell Mol Life Sci. 2013;70(4):631–59.
Forsyth CB, Shannon KM, Kordower JH, Voigt RM, Shaikh M, Jaglin JA, Estes JD, Dodiya HB, Keshavarzian A. Increased intestinal permeability correlates with sigmoid mucosa alpha-synuclein staining and endotoxin exposure markers in early Parkinson's disease. PLoS One. 2011;6(12):e28032.
Zhang R, Miller RG, Gascon R, Champion S, Katz J, Lancero M, Narvaez A, Honrada R, Ruvalcaba D, McGrath MS. Circulating endotoxin and systemic immune activation in sporadic amyotrophic lateral sclerosis (sALS). J Neuroimmunol. 2009;206(1-2):121–4.
Wang A, Keita AV, Phan V, McKay CM, Schoultz I, Lee J, Murphy MP, Fernando M, Ronaghan N, Balce D, et al. Targeting mitochondria-derived reactive oxygen species to reduce epithelial barrier dysfunction and colitis. Am J Pathol. 2014;184(9):2516–27.
Wang W, Uzzau S, Goldblum SE, Fasano A. Human zonulin, a potential modulator of intestinal tight junctions. J Cell Sci. 2000;113(Pt 24):4435–40.
Sapone A, de Magistris L, Pietzak M, Clemente MG, Tripathi A, Cucca F, Lampis R, Kryszak D, Carteni M, Generoso M, et al. Zonulin upregulation is associated with increased gut permeability in subjects with type 1 diabetes and their relatives. Diabetes. 2006;55(5):1443–9.
Svedlund J, Sjodin I, Dotevall G. GSRS--a clinical rating scale for gastrointestinal symptoms in patients with irritable bowel syndrome and peptic ulcer disease. Dig Dis Sci. 1988;33(2):129–34.
Chaplin A, Curless R, Thomson R, Barton R. Prevalence of lower gastrointestinal symptoms and associated consultation behaviour in a British elderly population determined by face-to-face interview. Br J Gen Pract. 2000;50(459):798–802.
Zuchelli T, Myers SE. Gastrointestinal issues in the older female patient. Gastroenterol Clin N Am. 2011;40(2):449–66. x
Snaith RP, Zigmond AS. The hospital anxiety and depression scale. Br Med J (Clin Res Ed). 1986;292(6516):344.
Roberts MH, Fletcher RB, Merrick PL. The validity and clinical utility of the hospital anxiety and depression scale (HADS) with older adult new Zealanders. Int Psychogeriatr. 2014;26(2):325–33.
Frändin K, Grimby G. Assessment of physical activity, fitness and performance in 76-year-olds. Scand J Med Sci Sports. 2007;4(1):41–6.
Palmieri B, Sblendorio V. Oxidative stress tests: overview on reliability and use. Part II. Eur Rev Med Pharmacol Sci. 2007;11(6):383–99.
R: A language and environment for statistical computing: R Core team. R Foundation for Statistical Computing. Vienna. 2016. [http://www.r-project.org].
Samuelsson G, McCamish-Svensson C, Hagberg B, Sundstrom G, Dehlin O. Incidence and risk factors for depression and anxiety disorders: results from a 34-year longitudinal Swedish cohort study. Aging Ment Health. 2005;9(6):571–5.
Schaub RT, Linden M. Anxiety and anxiety disorders in the old and very old--results from the berlin aging study (BASE). Compr Psychiatry. 2000;41(2 Suppl 1):48–54.
van Balkom AJ, Beekman AT, de Beurs E, Deeg DJ, van Dyck R, van Tilburg W. Comorbidity of the anxiety disorders in a community-based older population in the Netherlands. Acta Psychiatr Scand. 2000;101(1):37–45.
Walter S, Hallbook O, Gotthard R, Bergmark M, Sjodahl R. A population-based study on bowel habits in a Swedish community: prevalence of faecal incontinence and constipation. Scand J Gastroenterol. 2002;37(8):911–6.
Higgins PD, Johanson JF. Epidemiology of constipation in North America: a systematic review. Am J Gastroenterol. 2004;99(4):750–9.
Wald A, Scarpignato C, Mueller-Lissner S, Kamm MA, Hinkel U, Helfrich I, Schuijt C, Mandel KG. A multinational survey of prevalence and patterns of laxative use among adults with self-defined constipation. Aliment Pharmacol Ther. 2008;28(7):917–30.
Kelly JR, Kennedy PJ, Cryan JF, Dinan TG, Clarke G, Hyland NP. Breaking down the barriers: the gut microbiome, intestinal permeability and stress-related psychiatric disorders. Front Cell Neurosci. 2015;9:392.
Donini LM, Savina C, Cannella C. Nutrition in the elderly: role of fiber. Arch Gerontol Geriatr. 2009;49(Suppl 1):61–9.
Ganda Mall JP, Casado-Bedmar M, Winberg ME, Brummer RJ, Schoultz I, Keita AV. A beta-glucan-based dietary Fiber reduces mast cell-induced Hyperpermeability in ileum from patients with Crohn's disease and control subjects. Inflamm Bowel Dis. 2017;24(1):166–78.
Fasano A. Regulation of intercellular tight junctions by zonula occludens toxin and its eukaryotic analogue zonulin. Ann N Y Acad Sci. 2000;915:214–22.
Smecuol E, Sugai E, Niveloni S, Vazquez H, Pedreira S, Mazure R, Moreno ML, Label M, Maurino E, Fasano A, et al. Permeability, zonulin production, and enteropathy in dermatitis herpetiformis. Clin Gastroenterol Hepatol. 2005;3(4):335–41.
Vojdani A, Vojdani E, Kharrazian D. Fluctuation of zonulin levels in blood vs stability of antibodies. World J Gastroenterol. 2017;23(31):5669–79.
Ohlsson B, Orho-Melander M, Nilsson PM. Higher levels of serum Zonulin may rather be associated with increased risk of obesity and hyperlipidemia, than with gastrointestinal symptoms or disease manifestations. Int J Mol Sci. 2017;18(3):1-13.
Moreno-Navarrete JM, Sabater M, Ortega F, Ricart W, Fernandez-Real JM. Circulating zonulin, a marker of intestinal permeability, is increased in association with obesity-associated insulin resistance. PLoS One. 2012;7(5):e37160.
Condello G, Capranica L, Stager J, Forte R, Falbo S, Di Baldassarre A, Segura-Garcia C, Pesce C. Physical activity and health perception in aging: do body mass and satisfaction matter? A three-path mediated link. PLoS One. 2016;11(9):e0160805.
Keita AV, Gullberg E, Ericson AC, Salim SY, Wallon C, Kald A, Artursson P, Soderholm JD. Characterization of antigen and bacterial transport in the follicle-associated epithelium of human ileum. Lab Investig. 2006;86(5):504–16.
Hansson L, Zanchetti A, Carruthers SG, Dahlof B, Elmfeldt D, Julius S, Menard J, Rahn KH, Wedel H, Westerling S. Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the hypertension optimal treatment (HOT) randomised trial. HOT study group. Lancet. 1998;351(9118):1755–62.
Ittaman SV, VanWormer JJ, Rezkalla SH. The role of aspirin in the prevention of cardiovascular disease. Clin Med Res. 2014;12(3-4):147–54.
Bjarnason I, Williams P, Smethurst P, Peters TJ, Levi AJ. Effect of non-steroidal anti-inflammatory drugs and prostaglandins on the permeability of the human small intestine. Gut. 1986;27(11):1292–7.
Perez-Paramo M, Munoz J, Albillos A, Freile I, Portero F, Santos M, Ortiz-Berrocal J. Effect of propranolol on the factors promoting bacterial translocation in cirrhotic rats with ascites. Hepatology. 2000;31(1):43–8.
Tulstrup MV, Christensen EG, Carvalho V, Linninge C, Ahrne S, Hojberg O, Licht TR, Bahl MI. Antibiotic treatment affects intestinal permeability and gut microbial composition in Wistar rats dependent on antibiotic class. PLoS One. 2015;10(12):e0144854.
Wistrom J, Norrby SR, Myhre EB, Eriksson S, Granstrom G, Lagergren L, Englund G, Nord CE, Svenungsson B. Frequency of antibiotic-associated diarrhoea in 2462 antibiotic-treated hospitalized patients: a prospective study. J Antimicrob Chemother. 2001;47(1):43–50.