Metabolic endotoxemia refers to a situation in which unhealthy 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 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 great 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. And I believe that it is 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.
- 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.
The list of growing rapidly. It is also increasingly looking like increased LPS is virtually synonymous with small intestinal bacterial overgrowth, SIBO. The increased LPS levels associated with the proliferation of Gram-negative Enterobacteriaceae of SIBO likely accounts for why it is associated with, say, fibromyalgia and neurodegenerative conditions.
Killing off undesirable bacterial species during treatment for small intestinal bacterial overgrowth, SIBO, can really amp up metabolic endotoxemia temporarily. The flood of LPS is a big part of the reason why “die-off” reactions occur with SIBO treatment, as dying bacteria shed their cell wall LPS.
Unfortunately, because metabolic endotoxemia was first observed in mice fed a high-fat diet, this has led many to interpret this to mean that a high-fat diet in humans also cultivates the same. This is an overly-simplistic interpretation, as prebiotic and various probiotics can completely ‘turn off” the rise in blood LPS levels.
Prebiotic fibers are the heroes for reducing LPS blood levels, typically reducing levels by 20-50% or more. Of course, if SIBO is suspected or its presence confirmed, then this should be addressed before increasing prebiotic fiber intake, since prebiotic fibers can make you ill in the presence of SIBO. See my Undoctored Inner Circle for the in-depth SIBO Protocol we follow to eradicate SIBO, along with steps we take to enhance efficacy, while also addressing the common fungal overgrowth that co-exists in at least 50% of people with SIBO. Once accomplished, be sure to make prebiotic fiber intake the centerpiece of your dietary efforts to enjoy their wide and fabulous health benefits.