One of the few studies to directly implicate endotoxin (also known as LPS) in cancer progression. While there are other studies showing activation of the LPS receptor known as TLR4 is involved in cancer genesis and progression, there are many endogenous and exogenous substances that can activate TLR4 and as such the LPS connection to cancer was unclear in the past. This study is perhaps the first to demonstrate increased serum LPS in both human and animal patients with esophageal cancer (EC), and direct pro-cancer effects of LPS. This, of course, directly implies increased gut permeability, which has already been shown to be due to low NAD+ levels – i.e. it is driven by low oxidative metabolism. The same studies showing gut permeability to be riven by low NAD+ also demonstrated that the permeability can be reversed by supplementing NAD+ precursors such as niacinamide. If LPS is the main driver of EC (and, very likely, most other cancers) then supplementing with niacinamide could be a simple and cheap option to put the brakes on this (and possibly others) cancers, especially if combined with aspirin. That hypothesis has already been corroborated by my own studies with cancer, demonstrating the curative effects of combining B1, B3, and B7 vitamins with aspirin. And since my cancer studies use a very different type of tumor (human B cell lymphoma), one could reasonably conclude the LPS pro-cancer effects apply to many/most (all?) tumors and as such the remedies against LPS may be applicable to not just esophageal cancer.
https://www.nature.com/articles/s41598-024-63774-6
“…Here, we investigated the gut flora and metabolites of patients with esophageal squamous cell carcinoma and found abundant Bacteroides and increased secretion and entry of the surface antigen lipopolysaccharide (LPS) into the blood, causing inflammatory changes in the body. We confirmed these results in a mouse model of 4NQO-induced esophageal carcinoma in situ and further identified epithelial–mesenchymal transition (EMT) occurrence and TLR4/Myd88/NF-κB pathway activation in mouse esophageal tumors. Additionally, in vitro experiments revealed that LPS from Bacteroides fragile promoted esophageal cancer cell proliferation, migration, and invasion, and induced EMT by activating the TLR4/Myd88/NF-κB pathway. These results reveal that Bacteroides are closely associated with esophageal cancer progression through a higher inflammatory response level and signaling pathway activation that are both common to inflammation and tumors induced by LPS, providing a new biological target for esophageal cancer prevention or treatment.”
