E. coli as Driver & Treatment: IBD series

Escherichia coli, or E. coli, is a gram negative bacteria that is a common inhabitant in a healthy gut. However, certain strains of this particular species are known pathogens that can contribute to active inflammation and drive inflammatory bowel disease. Surprisingly, the treatment of certain inflammatory bowel disease cases is possible with certain non pathogenic E. coli probiotics. Read on to learn about how Escherichia coli can be a driver and a treatment for inflammatory bowel disease. 

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Inflammatory Bowel Disease 101

First off a quick overview on inflammatory bowel disease. 

Most IBD patients will fall into one of two categories. They will either have a diagnosis of Crohn’s disease or ulcerative colitis. Other subtypes of IBD include lymphocytic and collagenous colitis (1). 

While we still aren’t quite sure what causes inflammatory bowel disease, there are a number of leading theories. Keep in mind this is a constantly evolving area of research and we are only covering the broad strokes. 

One of the leading theories on IBD development involves a dysfunctional overactive immune response begins to target our resident microbiota (aka loss of tolerance). A second theory includes an altered microbiota (think overgrowths and infections) and/or a breakdown in the gut wall (aka leaky gut) resulting in a healthy immune response leading to inflammation and all of the symptoms of IBD (2).

Both of these theories hold water. 

Genetics and environment/lifestyle factors can set the stage for the development of IBD. With the genetic piece we can see an increased risk of the development of IBD when a family member has IBD. Studies on identical twins show an increased incidence of 37.3% for the development of Crohn’s disease and an increased incidence of 10% in ulcerative colitis when one twin develops IBD. 

The environmental/lifestyle factors may include 

  • Breastfeeding
  • Diet
  • Hygiene 
  • Smoking

Finally, the interplay between the mucosal immune system that lines the gut, the gut wall and the abundance of microbes that live in our digestive tract, brings everything together in a perfect storm leading to inflammatory bowel disease (3).   

Quick summary. Genes + environment + a dysregulated gut = IBD

Or in science speak ‘Inflammatory bowel disease (IBD) is a multifactorial disease which arises as a result of the interaction of genetic, environmental, barrier and microbial factors leading to chronic inflammation in the intestine‘ (4)

Treating Inflammatory Bowel Disease Naturally

While there isn’t much we can do about our genetic makeup we can intervene with diet, lifestyle and gut improving therapies to improve the symptoms and correct the drivers of inflammatory bowel disease. 

From the research available and clinical experience I see bacterial overgrowths, infections and alterations to the gut microbiome as a major place to step in and help steer the direction of inflammatory bowel disease. 

We can see bacterial diversity being lower in IBD patients. An overgrowth of the Enterobacteriaceae family as well as Fusobacterium and Enterococcus faecalis overgrowths are commonly found in Crohn’s disease patients. Finally a reduction in beneficials including bifidobacteria and key butyrate-producing bacteria are found in both Crohn’s disease and ulcerative colitis (5).

While I don’t think that there is one particular bacterial overgrowth or infection that causes or drives inflammatory bowel disease in every case (if only it were that simple!) I do see Escherichia coli overrepresented in many IBD patients when we screen their microbiome. 

Microbiome Testing in Inflammatory Bowel Disease 

The more unwell someone is, the stronger my recommendations for testing become

These tests aren’t cheap but provide some valuable information that often changes or refines the therapeutic recommendations. Often patients start to feel better sooner when we have all the information we need to accurately treat. 

Below are a few images of different IBD patient’s microbiome tests showing overgrowths of E. coli.  

Image taken from Microba showing a significant elevation in E. coli in a patient with ulcerative colitis 
Image taken from The Complete Microbiome Map showing significant elevations in E. coli in another patient with ulcerative colitis 

E. coli strains causing inflammation in IBD

E. coli is an odd bug. On one hand certain strains called pathotypes can be incredibly virulent causing diarrheal disease, urinary tract infections and sepsis or meningitis whereas other strains are healthy inhabitants of the gut as long as they remain in lower numbers. One strain of E. coli is even a probiotic. More on that shortly. 

Focusing in on the diarrheal disease causing E. colis we can see six different categories (6). Their actions on the gut wall can be seen in the image below 

  1. Enteropathogenic E. coli (EPEC)
  2. Enterohaemorrhagenic E. coli (EHEC)
  3. Enterotoxigenic E. coli (ETEC)
  4. Enteroaggregative E. coli (EAEC)
  5. Enteroinvasive E. coli (EIEC)
  6. Diffusely adherent E. coli (DAEC)
Image taken from: Pathogenic Escherichia coli showing the effects of different pathotypes of E. coli on the gut wall.

These strains of E. coli have the ability to colonise the mucous layer in the gut, evade our immune system and damage our cells. 

Researchers have been investigating E. coli as a driver of disease in IBD for decades.

Back in the late 90’s a research team found significant E. coli overgrowths from biopsies of the small intestine of Crohn’s disease patients concluding that E. coli could both initiate and chronically promote the inflammatory response in Crohn’s disease (7). 

In Crohn’s disease they have found a higher number of more virulent E. coli strains when patients relapse (8).

On the ulcerative colitis front we see E. coli as a possible driver of the inflammation as well. 

One study biopsied and assessed the colon mucosa of patients with active ulcerative colitis. They found a significant increase of E. coli in inflamed tissue in the ulcerative colitis group compared to the placebo group (9).

Now here is the interesting bit. The control group in the study above were patients diagnosed with diarrhoea predominant irritable bowel syndrome, showing that E. coli proliferation was significantly pronounced in the IBD group compared to patients experiencing IBS. 

Another study found E. coli to proliferate from the gut mucosal layer into the connective tissue (the lamina propria) in ulcerative colitis patients whereas, in normal controls, there was no E. coli found in this connective tissue layer (10). 

Image taken from: wikipedia

E. coli strains as a probiotic? 

After everything we have covered above it would be understandable to think of E. coli as a problematic bug, but the microbiome is not that straight forward. 

One particular strain of E. coli, isolated in 1917 by Alfred Nissle, has good evidence for use as a potent probiotic for IBD and bacterial infections. This strain, called Escherichia coli Nissle 1917 was first isolated from the stool of a German soldier who appeared to have resistance against diarrhoeal causing infections which were a big issue at the time (11).

Here in Australia it is available as a product called mutaflor.

E. coli Nissle 1917 deserves a whole article covering it’s actions and benefits on the gut ecosystem. A few key points are summarised in the image below showing this probiotics actions including

  • Direct antagonistic effects on pathogenic bacteria and yeasts
  • Improving colonisation resistance 
  • Improving gut permeability 
  • Immune modulating activities
  • Inhibiting certain pathogenic bacteria from invading the gut lining including Salmonella, Enteroinvasive E. coli (EIEC), Shigella, Yersinia, Listeria and Candida
Image taken from: Escherichia coli strain Nissle 1917—from bench to bedside and back: history of a special Escherichia coli strain with probiotic properties  

E. coli to treat Inflammatory Bowel Disease

Here is the interesting bit. E. coli Nissle 1917 has a decent amount of research showing benefit in IBD. Let’s cover this research now. 

The highest level of evidence we have are systematic reviews with meta-analysis. One such review published in the Journal of gastrointestinal and liver diseases in 2015 looked at the effects of E. coli Nissle 1917 in maintaining remission in ulcerative colitis patients. 

From the 6 studies including 719 patients they found that E. coli Nissle 1917 induced remission in 61.6% of patients compared to the standard treatment for ulcerative colitis which induced remission in 69.5% of patients. In the patients that took E. coli Nissle 1917 36.8% relapsed (very common in IBD) compared to 36.1% in the pharmaceutical arm. 

While there isn’t much published in E. coli Nissle 1917 and Crohn’s disease there is one interesting in-vitro study worth covering. 

Pathogenic E. coli strains were isolated from ileal lesions in Crohn’s disease patients. The researchers then incubated these pathogenic strains with Nissle 1917. They found that Nissle 1917 strongly inhibited the adherence of the pathogenic strains of E. coli to the cells that line the gut (13).

Is E. Coli Nissle 1917 safe as a Probiotic? 

As E. coli Nissle 1917 is the same species as the different pathotypes of E. coli it has been studied up and down to determine whether it is healthy for people to consume. 

A number of studies (summarised here) have demonstrated the safety of E. coli nissle 1917 showing that it 

  • Lack pathogenic adhesion factors
  • It does not produce any enterotoxins or cytotoxins
  • It is not invasive
  • It is not uropathogenic
  • It is rapidly killed by non-specific defense factors of blood serum. 

While E. coli Nissle 1917 is still a gram negative bacteria, and like all gram negative bacteria contains a bacterial endotoxin called lipopolysaccharide (LPS) in its membrane, Nissle 1917 is unique here as well.

The LPS found on the Nissle 1917 strain of E. coli is different when compared to all other E. coli strains that have been studied. The 06 polysaccharide side chain is very short and the oligosaccharide core segment of the LPS molecule has had some unique modifications as well (14). 

That microbiology speak may be too much detail (yes I am a nerd!) so let’s boil it down to brass tax. All strains of Escherichia coli contain an endotoxin that can set off the immune system. E. coli Nissle 1917 has this endotoxin but it is unique in the fact that it tends to promote immune modulating effects and does not demonstrate any immunotoxic effects

A Holistic Approach to treating Inflammatory Bowel Disease 

It is important to point out that diseases involving gut imbalances, immune dysregulation, genetic susceptibility and environmental triggers are complex. 

While there is research supporting the use of E. coli Nissle 1917 for IBD that doesn’t mean it is a cure all. 

When I approach IBD cases I like to consider 

  • Diet as a driver of the disease 
  • The microbiome balance (using advanced gut testing)
  • Intestinal permeability status (leaky gut)
  • Nutrient deficiencies that may be contributing the symptom picture 
  • Herbal medicines to lower inflammation and balance the gut 
  • Prebiotics and probiotics to help balance the gut

Often when I screen my IBD patients I see an overgrowth of Escherichia coli. Sometimes it is one of the many pathogenic E. coli strains we discussed above. Many times I will use the E. coli Nissle 1917 and generally see good effect but it is never the only thing I recommend to help balance the gut, lower inflammation, heal the mucous lining and improve health in general.

Now over to you. Do you suffer from IBD? What has helped in your healing journey? 

References & Resources

  1. Diagnostics of Inflammatory Bowel Disease
  2. The fundamental basis of inflammatory bowel disease
  3. Inflammatory bowel disease: cause and immunobiology
  4. Microbiota dysbiosis and barrier dysfunction in inflammatory bowel disease and colorectal cancers: exploring a common ground hypothesis
  5. Microbiota dysbiosis and barrier dysfunction in inflammatory bowel disease and colorectal cancers: exploring a common ground hypothesis
  6. Pathogenic Escherichia coli
  7. Presence of adherent Escherichia coli strains in ileal mucosa of patients with Crohn’s disease
  8. Escherichia coli Pathobionts Associated with Inflammatory Bowel Disease 
  9. Possible role of Escherichia coli in propagation and perpetuation of chronic inflammation in ulcerative colitis
  10. Molecular Characterization of Rectal Mucosa-associated Bacterial Flora in Inflammatory Bowel Disease
  11. Escherichia coli strain Nissle 1917—from bench to bedside and back: history of a special Escherichia coli strain with probiotic properties  
  12. Escherichia coli Nissle 1917 in Ulcerative Colitis Treatment: Systematic Review and Meta-analysis
  13. Inhibitory effect of probiotic Escherichia coli strain Nissle 1917 on adhesion to and invasion of intestinal epithelial cells by adherent–invasive E. coli strains isolated from patients with Crohn’s disease
  14. The non-pathogenic Escherichia coli strain Nissle 1917 – features of a versatile probiotic

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