The evidence is growing implicating SIBO as an important risk for heart disease. SIBO has potential to be among the most important cardiovascular risk factors of all, alongside consumption of foods that provoke small LDL and VLDL particles (wheat, grains, and sugars), insulin resistance, vitamin D deficiency, and inflammation. Cholesterol? That is so 1960s. Don’t let the obsession for cholesterol—rusty. outdated, imprecise, but hugely profitable—fool you. There are far better ways to manage risk for cardiovascular disease than the silly notion of cholesterol.

For those of you new to this conversation, I invite you to review the many discussions I’ve provided on the important issue of small intestinal bacterial overgrowth, or SIBO. The arguments are a bit convoluted but, if you understand them, you will have huge insight into heart disease and how to not have it. In a nutshell, SIBO is initiated by the loss of numerous beneficial species from the colon, species such as Lactobacillus reuteri and Faecalibacterium prausnitzii that are susceptible to common antibiotics. A 10-day course of amoxicillin, for instance, that you took 20 years ago for an upper respiratory infection, may have completely eliminated these beneficial species. These species were responsible for suppression of potentially pathogenic species, especially fecal microbes. Loss of healthy species therefore allows potentially pathogenic fecal species to proliferate. In many people (1 in 2 Americans, by my estimate), these microbes also ascend up the 24-feet of small intestine. The 4-5 feet of colon and 24-feet of small intestine therefore total nearly 30-feet of gastrointestinal tract filled with unhealthy microbes such as E. coli, Klebsiella, and Citrobacter, so-called Gram-negative species since they fail to stain with one of the dyes used in the process of Gram staining to visualize microbes under a microscope.

The failure to take up some of the dye in Gram staining is due to the unique composition of the cell walls of these microbes, cell walls rich in something called lipopolysaccharide, LPS, also called endotoxin. Endotoxin has the potential to enter the blood circulation, a situation labeled “endotoxemia.” Evidence generated since the original 2007 European report suggest that blood levels of LPS endotoxin are around 200-400% higher in people with this condition compared to healthy controls.

Newcomers to this conversation are often skeptical. “How can microbes living in the GI tract have effects on the heart or other faraway organs such as joints, muscle, liver, or brain?” After all, the bowels have no direct connection to these organs.

The key is endotoxemia. Numerous factors in modern life have conspired to increase blood levels of endotoxemia, a long list that includes:

  • Intestinal proliferation of Gram-negatives—the overgrowth of E. coli and other fecal microbes alone can damage the intestinal barrier (“tight junctions”), leading to increased endotoxemia in the bloodstream. Coupled with loss of beneficial microbial species, this is a major contributor to increased intestinal permeability.
  • Emulsifying agents—Food additives such as polysorbate 80 and carboxymethylcellulose, common in foods such as ice cream, also emulsify the small intestinal mucus barrier, allowing increased entry of LPS into the bloodstream. Some people unknowingly take N-acetyl cysteine, hoping for cognitive benefits but not realizing that it is a potent emulsifier of the intestinal mucus barrier. This is also true for polyethylene glycol (Miralax) commonly used as a “prep” before a colonoscopy, resulting in massive disruption of the intestinal mucus lining.
  • The gliadin protein of wheat—and related proteins of other grains such as the secalin of rye or the zein of corn. Evidence tells us that the gliadin protein of wheat increases intestinal permeability, the initiating factor in type 1 diabetes, rheumatoid arthritis, and other autoimmune conditions.
  • Lack of omega-3 fatty acids—The fatty acids, EPA and DHA, activate the intestinal enzyme, intestinal alkaline phosphatase, that helps deactivate LPS in the intestines.
  • Lack of vitamin D—Vitamin D is a major activator of the intestinal immune response. When vitamin D blood levels are low, intestinal immunity is impaired and LPS is allowed to enter the bloodstream.
  • Lack of prebiotic fibers that microbes convert to butyrate—A very important mediator of the intestinal mucus barrier and nutrition for intestinal cells.
  • Lack of oleic acid—Oleic acid is the omega-9 fatty acid rich in extra-virgin olive oil that leads to formation of the endocannabinoid, oleoylethanolamide (OEA), that supports the intestinal cellular lining.
  • Chlorinated drinking water—Yes, your municipality chlorinates water to eliminate pathogens, but the chlorine (or worse, chloramine) also emulsifies (breaks down) the intestinal barrier.

In short, we are surrounded by numerous factors that invite LPS endotoxin into the bloodstream.

We can recreate the effects of SIBO and endotoxemia on the organs of the body outside the GI tract by injecting LPS directly into people. Despite the potential fatal hazards of this maneuver, such studies have indeed been conducted. Here’s a graph from a study looking at what happens to 89 inflammatory mediators and cardiovascular risk factors with direct administration of LPS into the bloodstream (i.e., via injection, not originating from GI microbes), with 54 cardiovascular risk biomarkers surging with LPS in the bloodstream:

LPS-induced inflammation

Resi 2021

Other experimental evidence suggests that endotoxemia hugely drives formation and progression of coronary atherosclerotic plaque, i.e, coronary heart disease, heart attacks, angina, “need” for procedures such as stent implantation and bypass surgery—

As I have often said, the real tragedy of focusing on reducing saturated fat and reducing blood measures of cholesterol is that they take everyone’s attention away from the real causes of heart disease. Cholesterol is not a cause; it is a weak and indirect biomarker for some of the real causes of heart disease. The real causes are measurable, trackable, and manageable but the solutions are entirely nutritional and do not oblige the use of any pharmaceuticals. Thus, the silence and indifference of my colleagues, the drug industry, and people in healthcare, an industry built on profit, not on genuine health. Cardiovascular risk is a process that you have huge personal control over but the least knowledgeable person to consult is the doctor, as strategies that are available at little to no cost and involve non-pharmaceuticals or procedures are of no interest to them.

Identify SIBO, manage it, reduce endotoxemia, and you have been given an enormous advantage in reducing or eliminating risk for cardiovascular disease.