Metabolic Endotoxemia

Metabolic endotoxemia refers to a situation in which bowel flora species die and release something called lipopolysaccharide, or LPS, a component of their cell walls. LPS is released into the intestines, then cross the intestinal wall and enter the bloodstream. Because LPS is known to be toxic when it enters the bloodstream, it is labeled an “endotoxin” and, because it becomes blood-borne, it causes “endotoxemia.”

So-called Gram-negative bacteria that comprise approximately 70% of all bowel flora are the species that contain LPS. This includes species such as E. coli, Campylobacter, Klebsiella, Enterobacter, Citrobacter, Shigella, and others that are also potentially pathogenic, i.e., disease- and infection-causing. Only a decade ago, it was thought that higher blood levels of LPS only occurred with sepsis (blood infections) and ulcerative colitis. But it has since been demonstrated that common conditions such as obesity, insulin resistance, type 2 diabetes, fatty liver, neurodegenerative conditions and others all share higher LPS blood levels. LPS levels are not as high as that occurring with sepsis, i.e., overwhelming blood borne bacterial infection that complicates, for instance, pyelonephritis (bacterial kidney infection) or pneumonia. The more common situation of metabolic endotoxemia is associated with LPS levels that are typically no more than 10% of levels associated with sepsis, but more modest increases of LPS in the bloodstream nonetheless hold potential for adding to or causing health problems.

It is not clear what degree of intestinal dysbiosis is required for LPS levels to pose a risk to health. But it is virtually certain that SIBO, small intestinal bacterial overgrowth, yields an overwhelming quantity of LPS or metabolic endotoxemia, as this 30-foot length infection provides plenty of opportunity for Gram negative Enterobacteriaceae to shed LPS. It is also becoming clear that SIBO is now at epidemic levels in the U.S.

This chronic, 24-hour-a-day, low level of endotoxemia has real consequences outside of the dysbiosis and SIBO that create it. Among the conditions that are associated with increased blood levels of LPS are:

• Increased insulin resistance—There is a 35% reduction in insulin sensitivity, a process that contributes to weight gain and obesity, pre-diabetes and type 2 diabetes, and increased potential for heart disease, cancer, and dementia. Accordingly, people with type 2 diabetes have higher blood levels of LPS.
• Overweight and obesity—Increased levels of metabolic endotoxemia likely underlie the increase in numerous health conditions associated with excess weight.
• Fatty liver–The portal vein that receives the blood draining the intestines carries ten-fold higher levels of LPS than the systemic circulation, meaning the liver receives a large burden of this inflammatory mediator.
• Amyotrophic lateral sclerosis (Lou Gehrig’s Disease) and Alzheimer’s dementia—with 200-300% higher LPS levels that than in controls (keeping in mind that “healthy controls” are really not that healthy). LPS levels also correspond with severity of disease with levels increasing as disease progresses.
• Reduction in Bifidobacteria species that play a major role in preserving the intestinal barrier

The list of health conditions caused or worsened by metabolic endotoxemia is growing rapidly. Metabolic endotoxemia explains why dysbiosis and SIBO—obviously processes that occur within the intestinal walls—can “export” effects beyond the intestines and affect, for instance, joints, coronary arteries, skin, and brain. It is therefore a crucial process to manage. And there are indeed concrete steps you can take to minimize blood levels of LPS.

If you would like additional in-depth discussion on this important topic, see the Undoctored Advanced Topic: Metabolic Endotoxemia in our Undoctored Inner Circle.