• Robert T Mankowski, Ryan M Thomas, Dijoia B Darden, Raad Z Gharaibeh, Russell B Hawkins, Michael C Cox, Camille Apple, Dina C Nacionales, Ricardo F Ungaro, Marvin L Dirain, Fredrick A Moore, Christiaan Leeuwenburgh, Scott C Brakenridge, Thomas L Clanton, Orlando Laitano, Lyle L Moldawer, Alicia M Mohr, and Philip A Efron.
• Department of Aging and Geriatric Research, University of Florida College of Medicine, Gainesville, Florida.
• Shock. 2021 Apr 1; 55 (4): 519525519-525.

BackgroundOlder 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.MethodsMixed 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.ResultsNaive 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.ConclusionYoung 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.Copyright © 2020 by the Shock Society.

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