Septic Stability? Gut Microbiota in Young Adult Mice Maintains Overall Stability After Sepsis Compared to Old Adult Mice

Older adults have worse outcomes after sepsis than young adults. Additionally, alterations of the gut microbiota have been demonstrated to contribute to sepsis-related mortality. We sought to determine if there were alterations in the gut microbiota with a novel sepsis model in old adult mice, which...

Full description

Saved in:
Bibliographic Details
Published in:Shock (Augusta, Ga.) Vol. 55; no. 4; p. 519
Main Authors: Mankowski, Robert T, Thomas, Ryan M, Darden, Dijoia B, Gharaibeh, Raad Z, Hawkins, Russell B, Cox, Michael C, Apple, Camille, Nacionales, Dina C, Ungaro, Ricardo F, Dirain, Marvin L, Moore, Fredrick A, Leeuwenburgh, Christiaan, Brakenridge, Scott C, Clanton, Thomas L, Laitano, Orlando, Moldawer, Lyle L, Mohr, Alicia M, Efron, Philip A
Format: Journal Article
Language:English
Published: United States 01.04.2021
Subjects:
Age Factors
Animals
Female
Gastrointestinal Microbiome - physiology
Male
Mice
Mice, Inbred C57BL
Sepsis - microbiology
ISSN:1540-0514, 1540-0514
Online Access:Get more information
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Older adults have worse outcomes after sepsis than young adults. Additionally, alterations of the gut microbiota have been demonstrated to contribute to sepsis-related mortality. We sought to determine if there were alterations in the gut microbiota with a novel sepsis model in old adult mice, which enter a state of persistent inflammation, immunosuppression, and catabolism (PICS), as compared with young adult mice, which recover with the sepsis model. Mixed sex old (∼20 mo) and young (∼4 mo) C57Bl/6J mice underwent cecal ligation and puncture with daily chronic stress (CLP+DCS) and were compared with naive age-matched controls. Mice were sacrificed at CLP+DCS day 7 and feces collected for bacterial DNA isolation. The V3-V4 hypervariable region was amplified, 16S rRNA gene sequencing performed, and cohorts compared. α-Diversity was assessed using Chao1 and Shannon indices using rarefied counts, and β-diversity was assessed using Bray-Curtis dissimilarity. Naive old adult mice had significantly different α and β-diversity compared with naive adult young adult mice. After CLP+DCS, there was a significant shift in the α and β-diversity (FDR = 0.03 for both) of old adult mice (naive vs. CLP+DCS). However, no significant shift was displayed in the microbiota of young mice that underwent CLP+DCS in regards to α-diversity (FDR = 0.052) and β-diversity (FDR = 0.12), demonstrating a greater overall stability of their microbiota at 7 days despite the septic insult. The taxonomic changes in old mice undergoing CLP+DCS were dominated by decreased abundance of the order Clostridiales and genera Oscillospira. Young adult mice maintain an overall microbiome stability 7 days after CLP+DCS after compared with old adult mice. The lack of microbiome stability could contribute to PICS and worse long-term outcomes in older adult sepsis survivors. Further studies are warranted to elucidate mechanistic pathways and potential therapeutics.
Bibliography:ObjectType-Article-2
SourceType-Scholarly Journals-1
ObjectType-Feature-1
content type line 23
ISSN:1540-0514
1540-0514
DOI:10.1097/SHK.0000000000001648