Aging-induced dysbiosis worsens sepsis severity but is attenuated by probiotics in D-galactose-administered mice with cecal ligation and puncture model
Issued Date
2024-01-01
Resource Type
eISSN
19326203
Scopus ID
2-s2.0-85206810289
Pubmed ID
39423218
Journal Title
PloS one
Volume
19
Issue
10
Rights Holder(s)
SCOPUS
Bibliographic Citation
PloS one Vol.19 No.10 (2024) , e0311774
Suggested Citation
Pinitchun C., Panpetch W., Bhunyakarnjanarat T., Udompornpitak K., Do H.T., Visitchanakun P., Wannigama D.L., Udomkarnjananun S., Sukprasansap M., Tencomnao T., Tangtanatakul P., Leelahavanichkul A. Aging-induced dysbiosis worsens sepsis severity but is attenuated by probiotics in D-galactose-administered mice with cecal ligation and puncture model. PloS one Vol.19 No.10 (2024) , e0311774. doi:10.1371/journal.pone.0311774 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/101766
Title
Aging-induced dysbiosis worsens sepsis severity but is attenuated by probiotics in D-galactose-administered mice with cecal ligation and puncture model
Corresponding Author(s)
Other Contributor(s)
Abstract
INTRODUCTION: Despite the well-established effects of aging on brain function and gut dysbiosis (an imbalance in gut microbiota), the influence of aging on sepsis-associated encephalopathy (SAE) and the role of probiotics in this context remain less understood. METHODS: C57BL/6J mice (8-week-old) were subcutaneously administered with 8 weeks of D-galactose (D-gal) or phosphate buffer solution (PBS) for aging and non-aging models, respectively, with or without 8 weeks of oral Lacticaseibacillus rhamnosus GG (LGG). Additionally, the impact of the condition media from LGG (LCM) was tested in macrophages (RAW 264.7 cells), microglia (BV-2 cells), and hippocampal cells (HT-22 cells). RESULT: Fecal microbiome analysis demonstrated D-gal-induced dysbiosis (reduced Firmicutes and Desulfobacterota with increased Bacteroidota and Verrucomicrobiota), which LGG partially neutralized the dysbiosis. D-gal also worsens cecal ligation and puncture (CLP) sepsis severity when compared with PBS-CLP mice, as indicated by serum creatinine (Scr) and alanine transaminase (ALT), but not mortality, neurological characteristics (SHIRPA score), and serum cytokines (TNF-α and IL-6). Additionally, D-gal-induced aging was supported by fibrosis in the liver, kidney, and lung; however, CLP sepsis did not worsen fibrosis. Interestingly, LGG attenuated all parameters (mortality, Scr, ALT, SHIRPA, and cytokines) in non-aging sepsis (PBS-CLP) while improving all these parameters, except for mortality and serum IL-6, in aging sepsis (D-gal CLP). For the in vitro test using lipopolysaccharide (LPS) stimulation, LCM attenuated inflammation in some parameters on RAW264.7 cells but not BV-2 and HT-22 cells, implying a direct anti-inflammatory effect of LGG on macrophages, but not in cells from the brain. CONCLUSION: D-gal induced fecal dysbiosis and worsened sepsis severity as determined by Scr and ALT, and LGG could alleviate most of the selected parameters of sepsis, including SAE. However, the impact of LGG on SAE was not a direct delivery of beneficial molecules from the gut to the brain but partly due to the attenuation of systemic inflammation through the modulation of macrophages.