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

Background: 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. Methods: Mixed sex old (similar to 20 mo) and young (similar to 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. alpha-Diversity was assessed using Chao1 and Shannon indices using rarefied counts, and beta-diversity was assessed using Bray-Curtis dissimilarity. Results: Naive old adult mice had significantly different alpha and beta-diversity compared with naive adult young adult mice. After CLP+DCS, there was a significant shift in the alpha and beta-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 alpha-diversity (FDR = 0.052) and beta-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. Conclusion: 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.

Automated summary

Old adult mice showed significant alterations in gut microbiota after infection, while young adult mice maintained stability. These microbiota changes may contribute to worse outcomes in older adults after sepsis. Further research is needed to explore potential therapeutic targets.