Enhanced Bacteremia in Dextran Sulfate‐Induced Colitis in Splenectomy Mice Correlates with Gut Dysbiosis and LPS Tolerance
1
Issued Date
2022-02-01
Resource Type
ISSN
16616596
eISSN
14220067
Scopus ID
2-s2.0-85123686469
Pubmed ID
35163596
Journal Title
International Journal of Molecular Sciences
Volume
23
Issue
3
Rights Holder(s)
SCOPUS
Bibliographic Citation
International Journal of Molecular Sciences Vol.23 No.3 (2022)
Suggested Citation
Thim‐uam A., Makjaroen J., Issara‐amphorn J., Saisorn W., Wannigama D.L., Chancharoenthana W., Leelahavanichkul A. Enhanced Bacteremia in Dextran Sulfate‐Induced Colitis in Splenectomy Mice Correlates with Gut Dysbiosis and LPS Tolerance. International Journal of Molecular Sciences Vol.23 No.3 (2022). doi:10.3390/ijms23031676 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/83844
Title
Enhanced Bacteremia in Dextran Sulfate‐Induced Colitis in Splenectomy Mice Correlates with Gut Dysbiosis and LPS Tolerance
Other Contributor(s)
Abstract
Because both endotoxemia and gut dysbiosis post‐splenectomy might be associated with systemic infection, the susceptibility against infection was tested by dextran sulfate solution (DSS)‐ induced colitis and lipopolysaccharide (LPS) injection models in splenectomy mice with macrophage experiments. Here, splenectomy induced a gut barrier defect (FITC‐dextran assay, endotoxemia, bacteria in mesenteric lymph nodes, and the loss of enterocyte tight junction) and gut dysbiosis (increased Proteobacteria by fecal microbiome analysis) without systemic inflammation (serum IL‐6). In parallel, DSS induced more severe mucositis in splenectomy mice than sham‐DSS mice, as indicated by mortality, stool consistency, gut barrier defect, serum cytokines, and blood bacterial burdens. The presence of green fluorescent‐producing (GFP) E. coli in the spleen of sham‐DSS mice after an oral gavage supported a crucial role of the spleen in the control of bacteria from gut translocation. Additionally, LPS administration in splenectomy mice induced lower serum cytokines (TNF‐α and IL‐6) than LPS‐administered sham mice, perhaps due to LPS tolerance from pre‐existing post‐splenectomy endotoxemia. In macrophages, LPS tolerance (sequential LPS stimulation) demonstrated lower cell activities than the single LPS stimulation, as indicated by the reduction in supernatant cytokines, pro‐inflammatory genes (iNOS and IL‐1β), cell energy status (extracellular flux analysis), and enzymes of the glycolysis pathway (proteomic analysis). In conclusion, a gut barrier defect after splenectomy was vulnerable to enterocyte injury (such as DSS), which caused severe bacteremia due to defects in microbial control (asplenia) and endotoxemia‐induced LPS tolerance. Hence, gut dysbiosis and gut bacterial translocation in patients with a splenectomy might be associated with systemic infection, and gut‐barrier monitoring or intestinal tight‐junction strengthening may be useful.