REMOTE BURN INJURY IN AGED MICE INDUCES COLONIC LYMPHOID AGGREGATE EXPANSION AND DYSBIOSIS OF THE FECAL MICROBIOME WHICH CORRELATES WITH NEUROINFLAMMATION.
Journal
Shock (Augusta, Ga.)
ISSN: 1540-0514
Titre abrégé: Shock
Pays: United States
ID NLM: 9421564
Informations de publication
Date de publication:
01 10 2023
01 10 2023
Historique:
medline:
23
10
2023
pubmed:
7
8
2023
entrez:
7
8
2023
Statut:
ppublish
Résumé
The Earth's population is aging, and by 2050, one of six people will be 65 years or older. Therefore, proper treatment of injuries that disproportionately impact people of advanced age will be more important. Clinical studies reveal people 65 years or older account for 16.5% of all burn injuries and experience higher morbidity, including neurocognitive decline, and mortality that we and others believe are mediated, in part, by heightened intestinal permeability. Herein, we used our clinically relevant model of scald burn injury in young and aged mice to determine whether age and burn injury cooperate to induce heightened colonic damage, alterations to the fecal microbiome, and whether resultant changes in the microbiome correlate with neuroinflammation. We found that aged, burn-injured mice have an increase in colonic lymphoid aggregates, inflammation, and proinflammatory chemokine expression when compared with young groups and sham-injured aged mice. We then performed fecal microbiota sequencing and found a striking reduction in gut protective bacterial taxa, including Akkermansia , in the aged burn group compared with all other groups. This reduction correlated with an increase in serum fluorescein isothiocyanate-Dextran administered by gavage, indicating heightened intestinal permeability. Furthermore, loss of Akkermansia was highly correlated with increased messenger RNA expression of neuroinflammatory markers in the brain, including chemokine ligand 2, TNF-α, CXC motif ligand 1, and S100 calcium-binding protein A8. Finally, we discovered that postburn alterations in the microbiome correlated with measures of strength in all treatment groups, and those that performed better on the rotarod and hanging wire tests had higher abundance of Akkermansia than those that performed worse. Taken together, these findings indicate that loss of protective bacteria after burn injury in aged mice contributes to alterations in the colon, gut leakiness, neuroinflammation, and strength. Therefore, supplementation of protective bacteria, such as Akkermansia , after burn injury in aged patients may have therapeutic benefit.
Identifiants
pubmed: 37548929
doi: 10.1097/SHK.0000000000002202
pii: 00024382-202310000-00014
pmc: PMC10581426
mid: NIHMS1921319
doi:
Substances chimiques
Ligands
0
Chemokines
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
585-593Subventions
Organisme : NIA NIH HHS
ID : R01 AG018859
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM115257
Pays : United States
Organisme : NIGMS NIH HHS
ID : K08 GM134185
Pays : United States
Organisme : NIA NIH HHS
ID : T32 AG000279
Pays : United States
Organisme : BLRD VA
ID : I01 BX004335
Pays : United States
Organisme : NIA NIH HHS
ID : F32 AG082443
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM136444
Pays : United States
Informations de copyright
Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Shock Society.
Déclaration de conflit d'intérêts
The authors report no conflicts of interest.
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