From Very Low E.Coli to Very High E.Coli

CFS and IBS have very low E.Coli level, while UC and Crohn’s has very high E.Coli levels — yet I believe that the first syndromes leads to the second syndrome often. Now? The answer is simple, with very low E.Coli, the gut is not able to keep bad E.Coli at bay and they eventually “get lucky” and take over. Where does the bad E.Coli come from? Like food that you eat. The bad E.Coli is not so bad that it makes you immediately sick, instead, it just jacks your system a bit.

What we know

In my last post I described what we know about the bacteria shift and how the degree of shift reflects the severity of Crohn’s Disease and UC. In this post I want to just describe the strategy and criteria to address the dysfunctional microbiome. Our starting point is the table below. Then we try to define what fits our model and what we know about Crohn’s Disease.

Low indicates either low count or low diversity or both compared to healthy controls

Criteria for Selecting

Being trained in Operations Research, I am always inclined to develop models and work from there logically. Rather then tossing random medications, herbs and supplements at a condition, I want to define criteria that medications, herbs and supplements should fulfill (or if none can, then look for the best match at least). There can be some randomness — because what is important or not important can vary from MD to MD. These are my top concerns.

Criteria #1 Reduce the Very High without Hurting the Very Low

Given the large numbers of bacteria involved, it will be hard to find things that are perfect fits. Our worst case scenario will be something that reduces E.Coli but does not reduce Bifidobacteria.

Criteria #2 Anticoagulants are preferred over coagulants

This is also a carry over from the CFS  model that I thought should be checked. It appears  to apply to Crohn’s Disease. A few of many articles:

• “Our data suggest a new mechanism of platelet activation which has the potential to increase risk for thromboembolism in patients with active CD which might be due to platelets poised for thrombin-inducible activation.” Increased responsiveness to thrombin through protease-activated receptors (PAR)-1 and -4 in activeCrohn’s disease. [2013]
• Inflammatory bowel disease: epidemiology, pathology and risk factors for hypercoagulability.[2014]
• Continuous active state of coagulation system in patients with nonthrombotic inflammatory bowel disease. [2011]

Criteria #3 Histamine reducers are preferred over histamine raisers

Because coagulation will result in signals to mast cells to release heparin stored there, it also risks releasing heparin. In this case, the literature states:

“The results demonstrate highly elevated mucosal histamine levels of the large intestine in allergic enteropathy. In inflammatory bowel disease histamine content and secretion were found to be significantly increased particularly in affected mucosa of Crohn’s disease and ulcerative colitis than in unaffected tissue or in healthy controls. These findings give strong evidence that mast cell mediators like histamine play a role in the pathogenesis of these diseases. Mucosalhistamine is thus concluded to contribute to the immuno-inflammatory reactions of the intestine found in these disease states and to reflect the degree of colonic inflammation in Crohn’s disease and ulcerative colitis.” Mucosal histamine content and histamine secretion in Crohn’s disease, ulcerative colitis and allergic enteropathy. [1995]

This is actually important because E.Coli, especially those found in Crohn’s disease, are biofilm bacteria. Hence, we want to use EDTA and not NAC as a biofilm breaker.

Criteria #4 Preference for items that lowers TNF-Alpha

High TNF-alpha is associated with more severe Crohn’s disease and is a better indicator than C-Reactive Protein(a common inflammation marker) according to some studies

Criteria #5 No evidence of it being counter-indicated by actual studies

I tend to get picky when something is speculated to be harmful to a condition but there are no actual studies supporting the speculation. If there are actual studies — then it is a no-no, otherwise, all things should be considered.

A dear friend suffers from Crohn’s Disease and conventional treatments were not working for her – severe reactions to prescription medicine and significant neurological symptoms (which fortunately cleared when she stopped taking them). Her medical history path was:

1. Irritable Bowel Disease
2. 8 yrs later, Chronic Fatigue Syndrome (which went into remission using Jadin’s antibiotics protocol mixed with Hemex’s protocol)
   1. ” The findings also show that exposure to antibiotics increases Crohn’s-disease-associated dysbiosis”[2014]
3. 8 yrs later, Crohn’s Disease diagnosis

She asked me to find alternatives – and in one way, I owe her a very great thanks. Why, it was finding that Mutaflor (E.Coli Nissle 1917) was very effective for Crohn’s that lead me to getting some for her. When I got CFS and started reviewing the literature and conference proceeding that I read about the very low level of E.Coli found in CFS patients that I tried Mutaflor on a whim (from her stock). The rest is history on this blog.

I had put together an eBook on an alternative treatment for Crohn’s Disease — using PubMed literature only. It has been 18 months since I did the research. It is time to revise the book with the last 18 months of new findings on PubMed. I intend to effectively do a draft revision on this blog, adding new citations to the revision (but not including the original citations)

This is actually of interest to IBS and CFS patients, because, I believe these patients have a major risk of progressing to ulcerative colitis, Crohn’s disease or other forms of inflammatory bowel disease.

Back to my friend, she had a MRI done last month, and as with every one since she started my alternative proposal, her MRI is constantly better (with no prescript drugs being used).

The Proposal

Crohn’s Disease or Syndrome is a form of inflammatory bowel disease. It is often progressive and difficult to treat. A 2007 study reported that “Of all invasive bacterial strains in Crohn’s Disease (CD), 98.9% were identified as Escherichia Coli as opposed to 42.1% in Ulcerative Colitis (UC) and 2.1% in normal controls.” Other studies reported two other species overgrowth: bacteroides fragilis and peptostreptococcus. Low levels of faecalibacterium praunsitzii and bifidobacteria are reported [2014].

An important rhetorical question is “Does the disease cause the gut flora alteration, or does the gut flora alteration cause the disease symptoms?” Reviewing articles on PubMed, I could not locate any studies where attempts to concurrently correct all of the gut bacteria dysfunction were done. The term concurrent is not insignificant because gut bacteria displays a friend-foe behavior. Some bacteria are known to create virus to attack other members of its own family. Attempts to alter one species may fail because the other species may strive to restore the prior status-quo. A 2014 study did find that the shifts in bacteria “correlates strongly with disease status“.

A review of some successful treatments for CD and UC reveals that many attack invasive E. coli species. For example, E.Coli Nissle 1917 (Mutaflor) outcompetes many (but not all) E.Coli species and has been demonstrated to maintain remission. Various antibiotics are effective against some E.Coli species, with a triple antibiotic combination (ciprofloxacin, tetracycline, and trimethoprim) resulting in a 97% effectiveness against E.Coli species in the laboratory with no clinical trials reported for this combination. This study found that the antibiotic rifampin eliminated 85% of the species. This agrees with reports from other studies reporting varying success of this antibiotic for CD8. Similar results are seen with Rifaximin, a member of the rifampin family.

E. Coli is a difficult bacteria to eliminate. Many antibiotics have significant impact on beneficial species in multiple families which can result in easy establishment of other invasive species. Fecal transplants for CD are being trialed at the Centre for Digestive Diseases in Australia.

Recently there have been several studies of traditional medicines (“herbs”) where items were identified to be effective against E.Coli. This book looks at the possible use of herbs and probiotics to correct the reported gut bacteria dysfunction seen in CD.

Fecal Transplants

There have been a significant number of studies reporting success. including:

• Fecal Microbiota Transplantation Inducing Remission in Crohn’s Colitis and the Associated Changes in Fecal Microbial Profile. [2014]
• Fecal microbiota transplantation for severe enterocolonic fistulizing Crohn’s disease.[2013]
• Systematic review: faecal microbiota transplantation in the management of inflammatory boweldisease.[2012]

And on the negative side, there are some risks:

• Bacteremia as an adverse event of fecal microbiota transplantation in a patient with Crohn’s disease and recurrent Clostridium difficile infection. [2014]

“After FMT, the modification of the composition of the microbiota can be seen with an increase in the presence of the Bacteroidetes and Firmicutes species”

There are some reviews on the transplants for related conditions:

• “FMT seems efficacious and safe for the treatment of recurrent CDI. Hospitals should encourage the development of fecaltransplantation programs to improve therapy of local patients.” Fecal Microbiota Transplantation for the Treatment of Clostridium difficile Infection: A Systematic Review[2014]
• “The cumulative clinical resolution following four or more FMTs was 86 %. When antibiotic therapy was used between FMTs, the clinical resolution rate increased to 92 %. There were no reported adverse events and no patients who were cured with FMT had further episodes of CDI at 6-24 months follow-up. Multiple FMTs administered through enemas is an effective, safe, and simple therapy for the management of recurrent or refractory CDI.” The outcome and long-term follow-up of 94 patients with recurrent and refractory Clostridium difficile infection using single to multiple fecal microbiota transplantation via retention enema.[2014]

While I believe the benefit/risk ratio is very favorable, the newness of this therapy and the lack of large scale studies will result in reluctance by many MDs to advocate or perform this procedure.  The nature of this therapy and ‘Victorian Sense of cleanliness’ may result in a very slow adoption and even banning by law (due to it’s grossness — not due to any science). Note: FMT has shown the same effectiveness for Chronic Fatigue Syndrome.

This leads us to a second approach (which can be done concurrently with the above) – modifying via probiotics. “After FMT, the modification of the composition of the microbiota can be seen with an increase in the presence of the Bacteroidetes and Firmicutes species” [2014]. If we can induce the same shift via prebiotics, appropriate foods and probiotics then FMT may not be needed. Even if FMT is done, I believe that monthly analysis (via ubione, etc) is strongly recommended and appropriate supplementation done.  This is my focus.

Better Microbiome Analysis

Over the last year new technology and citizen scientist initiatives (http://americangut.org/ , http://ubiome.com/)have provided greater insight into the bacteria shifts. What do we know today? An excellent start is this 2014 paper, The Treatment-Naive Microbiome in New-Onset Crohn’s Disease

Low indicates either low count or low diversity or both compared to healthy controls

Graphics

From: The Treatment-Naive Microbiome in New-Onset Crohn’s Disease [2014]

That’s it for this post, next is looking at the E.Coli dimension and what can be done about it.