Endotoxemia and Gastrointestinal Cancers: Insight into the Mechanisms Underlying a Dangerous Relationship

Abstract

Lipopolysaccharide (LPS), also known as endotoxin, is a component of the membrane of gram-negative bacteria and a well-recognized marker of sepsis. In case of disruption of the intestinal barrier, as occurs with unhealthy diets, alcohol consumption, or during chronic diseases, the microbiota residing in the gastrointestinal tract becomes a crucial factor in amplifying the systemic inflammatory response. Indeed, the translocation of LPS into the bloodstream and its interaction with toll-like receptors (TLRs) triggers molecular pathways involved in cytokine release and immune dysregulation. This is a critical step in the exacerbation of many diseases, including metabolic disorders and cancer. Indeed, the role of LPS in cancer development is widely recognized, and examples include gastric tumor related to Helicobacter pylori infection and hepatocellular carcinoma, both of which are preceded by a prolonged inflammatory injury; in addition, the risk of recurrence and development of metastasis appears to be associated with endotoxemia. Here, we review the mechanisms that link the promotion and progression of tumorigenesis with endotoxemia, and the possible therapeutic interventions that can be deployed to counteract these events.

Oleanolic acid improved intestinal immune function by activating and potentiating bile acids receptor signaling in E. coli-challenged piglets

“…Young animals infected with ETEC often die due to severe watery diarrhea and rapid dehydration, resulting in immediate financial loss to farmers [ 40 ]. After entering the intestine, ETEC can use bacterial surface adhesins to adhere to the IECs and secrete enterotoxins, causing intestinal inflammation and injury [ 41 ] and even endotoxemia or systemic infection [ 42 ]. Since the prohibition of antibiotics in livestock production, there has been a lack of effective nutritional measures available to mitigate ETEC infections.…”

Role of the gut microbiota in tumorigenesis and treatment

“…The impairment of the gut barrier promotes hepatic inflammation, fibrosis, proliferation and the activation of antiapoptotic signals by activating LPS and its receptor TLR. This process thereby facilitates the development of HCC (Figure 4 ) 131 , 138 . Administering dextran sulfate sodium disrupts the gut barrier, which not only results in increased systemic LPS levels and liver fibrosis but also promotes HCC formation in mice 139 .…”

Gut Microbiota, LADA, and Type 1 Diabetes Mellitus: An Evolving Relationship

“…Alterations in the gut microbiota and their repercussions at the metabolic level play a key role in the development of type 2 diabetes mellitus [ 15 , 16 ]. Changes in microbiota composition and gut dysbiosis increase gut inflammation and directly induce endotoxemia, which is recognized as a conditioning promoter of infectious, chronic, and metabolic diseases and has also gained importance in cancer pathogenesis [ 17 ]. Recent studies have highlighted the link between type 2 diabetes mellitus and metabolic endotoxemia.…”