Polypharmacy With High Drug Burden Index (DBI) Alters the Gut Microbiome Overriding Aging Effects and Is Reversible With Deprescribing.
Anticholinergics
Frailty
Gut microbiota
Sedatives
Journal
The journals of gerontology. Series A, Biological sciences and medical sciences
ISSN: 1758-535X
Titre abrégé: J Gerontol A Biol Sci Med Sci
Pays: United States
ID NLM: 9502837
Informations de publication
Date de publication:
24 02 2023
24 02 2023
Historique:
received:
29
05
2022
pubmed:
21
9
2022
medline:
3
3
2023
entrez:
20
9
2022
Statut:
ppublish
Résumé
Aging, medication use, and global function are associated with changes in the microbiome. However, their interrelationships and changes over time require further characterization. In a longitudinal aging mouse study, we investigated the effects of aging, chronic polypharmacy with a high Drug Burden Index (DBI, measure of total anticholinergic and sedative medication exposure) and gradual cessation (deprescribing) on the microbiome, further exploring any association with global outcomes. Chronic administration of high DBI polypharmacy attenuated the aging-related reduction in alpha diversity, which was not sustained after deprescribing. Beta diversity and LEfSe (Linear discriminant analysis Effect Size) features varied with age, polypharmacy, and deprescribing. Aging with and without polypharmacy shared decreases in Bifidobacteriaceae, Paraprevotellaceae, Bacteroidaceae, and Clostridiaceae, while only aging with polypharmacy showed increased LEfSe features. Microbiome diversity correlated with frailty, nesting, and open field performance. Polypharmacy deprescribing reversed changes that occurred with treatment. However, the microbiome did not recover to its pretreatment composition at 12 months, nor develop the same aging-related changes from 12 to 24 months as the control group. Overall, aging, chronic polypharmacy, and deprescribing differentially affected the diversity and composition of the gut microbiome, which is associated with frailty and function.
Identifiants
pubmed: 36124741
pii: 6702649
doi: 10.1093/gerona/glac195
pmc: PMC9951051
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
213-222Informations de copyright
© The Author(s) 2022. Published by Oxford University Press on behalf of The Gerontological Society of America.
Références
Front Nutr. 2017 Jul 24;4:34
pubmed: 28791292
PLoS One. 2010 May 17;5(5):e10667
pubmed: 20498852
Brain Behav Immun. 2015 Aug;48:186-94
pubmed: 25882912
Microbiome. 2017 Aug 9;5(1):95
pubmed: 28793934
Transl Psychiatry. 2021 Feb 18;11(1):131
pubmed: 33602895
Microbiome. 2020 Mar 14;8(1):36
pubmed: 32169105
Pharmacotherapy. 2020 Oct;40(10):1042-1053
pubmed: 33078479
J Gerontol A Biol Sci Med Sci. 2015 Aug;70(8):989-95
pubmed: 25733718
J Gerontol A Biol Sci Med Sci. 2021 May 22;76(6):1010-1018
pubmed: 32147704
Aging Clin Exp Res. 2020 Oct;32(10):2001-2011
pubmed: 31656031
J Am Assoc Lab Anim Sci. 2008 Nov;47(6):25-31
pubmed: 19049249
Arch Gerontol Geriatr. 2018 Sep - Oct;78:213-220
pubmed: 30015057
Gastroenterology. 2021 Jan;160(2):507-523
pubmed: 33307030
Mucosal Immunol. 2016 Nov;9(6):1418-1428
pubmed: 26906406
Med J Aust. 2012 Jan 16;196(1):50-3
pubmed: 22256935
Nature. 2018 Mar 29;555(7698):623-628
pubmed: 29555994
J Gerontol A Biol Sci Med Sci. 2021 May 22;76(6):1019-1028
pubmed: 32064521
Sci Rep. 2017 Sep 11;7(1):11102
pubmed: 28894183
BMC Microbiol. 2009 Jun 09;9:123
pubmed: 19508720
Nature. 2021 Dec;600(7889):500-505
pubmed: 34880489
Nat Commun. 2020 Jan 17;11(1):362
pubmed: 31953381
Cell Host Microbe. 2019 Nov 13;26(5):650-665.e4
pubmed: 31726029
Genome Med. 2016 Jan 29;8(1):8
pubmed: 26822992
J Pers Med. 2021 Mar 12;11(3):
pubmed: 33809103
Nat Methods. 2016 Jul;13(7):581-3
pubmed: 27214047
Proc Natl Acad Sci U S A. 2011 Mar 15;108 Suppl 1:4554-61
pubmed: 20847294
J Gerontol A Biol Sci Med Sci. 2017 Oct 12;72(11):1474-1482
pubmed: 28444190
PLoS One. 2013 Apr 22;8(4):e61217
pubmed: 23630581
BMC Microbiol. 2016 May 25;16:90
pubmed: 27220822
Front Microbiol. 2020 Feb 21;11:219
pubmed: 32153527
Med J Aust. 2019 Jul;211(2):71-75
pubmed: 31219179
Microbiome. 2016 Aug 08;4(1):42
pubmed: 27502158
Arch Intern Med. 2007 Apr 23;167(8):781-7
pubmed: 17452540
Clin Interv Aging. 2014 Sep 09;9:1503-15
pubmed: 25246778
Pharmacol Res Perspect. 2020 Jun;8(3):e00601
pubmed: 32476298
Br J Clin Pharmacol. 2020 Oct;86(10):1912-1920
pubmed: 32644249
Sci Transl Med. 2018 Nov 14;10(467):
pubmed: 30429354
Gastroenterology. 2022 Oct;163(4):1038-1052
pubmed: 35788347
Pharmacol Rev. 2004 Jun;56(2):163-84
pubmed: 15169926
mSystems. 2019 May 14;4(4):
pubmed: 31098397
Age (Dordr). 2014 Apr;36(2):583-92
pubmed: 24122289
J Proteome Res. 2017 May 5;16(5):1900-1910
pubmed: 28378586
Clin Pharmacol Ther. 2009 Jan;85(1):86-8
pubmed: 19037203
World J Gastroenterol. 2018 Nov 14;24(42):4750-4758
pubmed: 30479462
Sci Rep. 2022 Feb 9;12(1):2168
pubmed: 35140291
Nat Methods. 2012 Mar 04;9(4):357-9
pubmed: 22388286
Nature. 2012 Aug 9;488(7410):178-84
pubmed: 22797518
JAMA Intern Med. 2015 May;175(5):827-34
pubmed: 25798731
Genome Biol. 2011 Jun 24;12(6):R60
pubmed: 21702898
Front Microbiol. 2019 Sep 04;10:1947
pubmed: 31551944
Fundam Clin Pharmacol. 2007 Jun;21(3):217-30
pubmed: 17521291
J Gerontol A Biol Sci Med Sci. 2014 Jun;69(6):621-32
pubmed: 24051346
Heart. 2019 Jul;105(13):975-981
pubmed: 30988003
Nat Biotechnol. 2019 Aug;37(8):852-857
pubmed: 31341288
Microbiome. 2014 Dec 05;2(1):50
pubmed: 25520805