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I consider bacterial translocation from the gut, aka, metabolic endotoxemia, the key to understanding chronic conditions like diabetes and cardiovascular disease. Gut pathogens and large food molecules that breach the gut wall provoke inflammatory immune responses that negatively impact the liver and other organs throughout the body, including the brain.

For those of you who read my heart disease series, you know that I believe the most likely source of endotoxins responsible for atherosclerosis emanate from the small intestine. Today I want to post about a Chinese rodent study published in 2012 that corroborates that view. (1)

As always, what’s true for an animal model may not be applicable to humans. However, there’s good reason to believe these observations also hold true for us.

This study explored how sepsis affected bacterial transmission from the intestinal tract to systemic circulation. What makes blood infections so life threatening is the intense immune and stress responses provoked. These responses disassemble intestinal tight junctions causing translocation of gut pathogens that in turn provoke even greater inflammatory immune responses and cortisol release in a feed-forward manner.

Stopping this feedback loop makes treating sepsis very, very challenging. It’s one reason mortality rates from blood infections are depressingly high.

Metabolic endotoxemia is, in my estimation, a form of low-grade, chronic sepsis that remains mostly under control due to immune-cell complexes in the intestinal tract and liver. Yet unlike sepsis, blood poisoning is not the end result. Nevertheless, the provocation of chronic intestinal and liver inflammation coupled with lipid peroxidation and chronic cortisol release does lead to long-term health consequences, many of which I’ve written about over the past six months.

While the causes differ between these conditions, the sepsis disease model can help us understand which sections of the intestinal tract are most prone to increased intestinal permeability when subjected to the stress of gut dysbiosis. So with that as prologue, let’s see what these researchers found.

A pathogenic strain of gram-negative E. coli was used in this study. As you recall, gram-negative bacteria contain lipopolysaccharides (LPSs) which initiate intense immune responses. To trace its translocation in these animals, a green fluorescent protein was paired with the E. coli.

A total of ninety Spague-Dawley rats were chosen for this trial based on their lack of kanamycin-resistant bacteria. Kanamycin is an antibiotic and was used to sterilize their guts and prepare them for E. coli colonization.

All rats underwent surgery for the implantation of an enterogastric tube. These are tubes inserted through the abdomen with their terminus in the intestine.

Thirty rats had tubes inserted into the middle part of their small intestine (jejunum). Thirty others had tubes inserted into the last section of their small intestine (ileum). The last group of thirty had tubes inserted into their colons.

These rats were then divided as follows: ten rats were assigned to a blank group, ten to a control group, and ten to the E. coli group henceforth known as the lipopolysaccharide group (LPS group). After surgery, sterile water containing kanamycin was injected into the enterogastric tubes of all rats for three days.

On the fourth day, those rats placed in both the control and LPS group, were given a solution containing E. coli through these same tubes. Rats in the blank group were just given saline. This went on for two days.

After this, rats in the LPS group were given an intraperitoneal (body cavity) injection of E. coli to induce sepsis. The rats in the control and blank group were injected with a saline solution instead.

Lactulose and mannitol were given to all rats to assess levels of “leaky gut” via a six-hour collection of urine. Animals were then “sacrificed.”


Courtesy: Lipopolysaccharide-Induced Bacterial Translocation Is Intestine Site-Specific and Associates with Intestinal Mucosal Inflammation

Courtesy: Lipopolysaccharide-Induced Bacterial Translocation Is Intestine Site-Specific and Associates with Intestinal Mucosal Inflammation


These slides show translocation, or lack thereof, of E. coli to four organs. Slides (a) to (d) are the blank group, (e) to (h) are the control group, and (i) to (l) are the LPS group. Vertical columns from left to right are images of the following sites: intestines, mesenteric lymph node, liver and spleen.

The arrows indicate locations of translocated E. coli. The only group to show this was the LPS group. This shouldn’t be surprising as it would have been much too soon for the control group whose guts were also colonized with E. coli to develop endotoxemia as a result of depleted beneficial gut bacteria.




This is an electron transmission micrograph of intestinal tight junction status. Slides (a) to (c) are the blank group, (d) to (f) the control group, and (g) to (i) the LPS group. In both the blank and control groups, tight junctions remained closed. Not the case with the LPS group, however, where junctions were wide open (see arrows) thus confirming that sepsis disrupts gut-barrier function.




This graph plots the percentage of open intestinal tight junctions. For the purposes of today’s post, the LPS group is the only group of interest. While tight junctions were open in all three sections of the gastrointestinal tract, the ileum had the highest percentage and was the greatest source of endotoxins.


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This chart looks at the source of gut leakiness as measured by urinary excretion of lactulose and mannitol. This echoes the same finding as the previous illustration with most “leakiness” emanating from the ileum and jejunum.




These three graphs chart interleukin 10, interleukin 6 and tumor necrosis factor alpha levels in rat mucosal cells. Once again, the ileum had the highest levels, the colon the least.

As I said, while the cause of intestinal permeability in this study differs from what occurs in metabolic endotoxemia, its finding that the small intestine, and specifically the ileum, is the most likely source of endotoxin translocation when the body is subjected to elevated cytokine and stress levels is quite revealing.

From these results, we can see that the colon is far better able to neutralize endotoxins than the small intestine. This makes perfect sense as the colon has the highest bacterial concentrations in the GI tract and would be expected to contain them best.

In humans it is known that the colon has higher electrical resistance to permeability in contrast to the small intestine. It is also resistant to the passive movement of positively or negatively charged molecules (ions) through the gut wall. Finally, the colon is less susceptible to inflammatory injury than the small intestine.

Now obviously, in those with inflammatory disorders of the large bowel, levels of endotoxin translocation are quite high. Even in this study, permeability from the colon was significantly greater than in controls. Nevertheless, this study suggests that increased intestinal permeability is more likely to occur in the small intestine.

In my small intestinal bacterial overgrowth (SIBO) series, I noted that the overwhelming majority of bacterial infections affect the ileum and jejunum as a result of gut pathogens migrating from the colon due to impaired intestinal peristalsis. This makes perfect sense as the colon is adjacent to the ileum.

However, this study suggests that an additional mechanism may be at work in the development of SIBO. Regardless of where along the intestinal tract dysbiosis first takes hold, the inflammatory responses this initiates will in turn react back on the ileum and disrupt tight junctions here first and foremost. Once this occurs, it’s only a matter of time before increased intestinal permeability begins provoking immune responses in this part of the gastrointestinal tract.

Oxidative gut-wall environments caused by chronic immune activation favors the growth of pathogens and reduces or eliminates beneficial bacterial strains like lactobacillus that are unable to survive, let alone thrive in such conditions. Throw in impaired intestinal peristalsis and/or compromised gastric-barrier function, not to mention poor dietary choices, and the stage is set for metabolic endotoxemia,

Any bacterial theory of cardiovascular disease, diabetes, liver disorders, obesity, autism, ulcerative colitis, autoimmune disorders, etc. would do well to concentrate on the health, or lack thereof, of the small intestine. This study illustrates why it’s so important to study the digestive tract as a unified whole and not make the error of compartmentalizing gastrointestinal disorders by physical location alone. Gut flora disturbances anywhere along the length of the digestive track have knock-on effects elsewhere, especially the ileum and jejunum. Failure to recognize that can make resolving gut issues and the chronic diseases that flow from them very difficult.


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