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Obesity Alters cytokine signaling and gut microbiome in septic mice.

ABSTRACT: Sepsis is a leading cause of mortality. Plasma cytokine levels may identify those at increased risk of mortality from sepsis. Our aim was to understand how obesity alters cytokine levels during early sepsis and its correlation with survival. Six-week-old C57BL/6 male mice were randomized to control (non-obese) or high fat diet (obese) for 5-7 weeks. Sepsis was induced by cecal ligation and perforation (CLP). Cytokine levels were measured from cheek bleeds 8 h after CLP, and mice were monitored for survival. Other cohorts were sacrificed 1 h after CLP for plasma and tissue. Septic obese mice had higher survival. At 8 h after sepsis, obese mice had higher adiponectin, leptin, and resistin but lower TNFα and IL-6 compared to non-obese mice. When stratified by 24-h survival, adipokines were not significantly different in obese and non-obese mice. TNFα and IL-6 were higher in non-obese, compared to obese, mice that died within 24 h of sepsis. Diet and to sepsis significantly impacted the cecal microbiome. IL-6 is a prognostic biomarker during early sepsis in non-obese and obese mice. A plausible mechanism for the survival difference in non-obese and obese mice may be the difference in gut microbiome and its evolution during sepsis.

SUBMITTER: Bodilly L

PROVIDER: S-EPMC10621470 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature

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Obesity Alters cytokine signaling and gut microbiome in septic mice.

Bodilly Lauren L Williamson Lauren L Lahni Patrick P Alder Matthew N MN Haslam David B DB Kaplan Jennifer M JM

Innate immunity 20231006 8

Sepsis is a leading cause of mortality. Plasma cytokine levels may identify those at increased risk of mortality from sepsis. Our aim was to understand how obesity alters cytokine levels during early sepsis and its correlation with survival. Six-week-old C57BL/6 male mice were randomized to control (non-obese) or high fat diet (obese) for 5-7 weeks. Sepsis was induced by cecal ligation and perforation (CLP). Cytokine levels were measured from cheek bleeds 8 h after CLP, and mice were monitored f ...[more]

PMID: 37802127

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Project description:Sepsis has a high mortality rate, and treating sepsis remains a significant challenge worldwide. In former studies, our group found that traditional Chinese medicine, Shen FuHuang formula (SFH), is a promising medicine in treating coronavirus disease 2019 (COVID-19) patients with the septic syndrome. However, the underlying mechanisms remain elusive. In the present study, we first investigated the therapeutic effects of SFH on septic mice. To investigate the mechanisms of SFH-treated sepsis, we identified the gut microbiome profile and exploited untargeted metabolomics analyses. The results demonstrated that SFH significantly enhanced the mice's 7-day survival rate and hindered the release of inflammatory mediators, i.e., TNF-α, IL-6, and IL-1β. 16S rDNA sequencing further deciphered that SFH decreased the proportion of Campylobacterota and Proteobacteria at the phylum level. LEfSe analysis revealed that the treatment of SFH enriched Blautia while decreased Escherichia_Shigella. Furthermore, serum untargeted metabolomics analysis indicated that SFH could regulate the glucagon signaling pathway, PPAR signaling pathway, galactose metabolism, and pyrimidine metabolism. Finally, we found the relative abundance of Bacteroides, Lachnospiraceae_NK4A136_group, Escherichia_Shigella, Blautia, Ruminococcus, and Prevotella were closely related to the enrichment of the metabolic signaling pathways, including L-tryptophan, uracil, glucuronic acid, protocatechuic acid, and gamma-Glutamylcysteine. In conclusion, our study demonstrated that SFH alleviated sepsis by suppressing the inflammatory response and hence reduced mortality. The mechanism of SFH for treating sepsis may be ascribed to the enrichment of beneficial gut flora and modulation in glucagon signaling pathway, PPAR signaling pathway, galactose metabolism, and pyrimidine metabolism. To sum up, these findings provide a new scientific perspective for the clinical application of SFH in treating sepsis.

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Obesity Alters cytokine signaling and gut microbiome in septic mice.

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Obesity Alters cytokine signaling and gut microbiome in septic mice.

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