Monthly Archives: May 2014

Unknown's avatar lassesen 10:05 pm on May 26, 2014  

Microbiome: Doctor’s Data Lab Analysis 2014-05-14

Another reader asked me to review and provide comments for their CFS MD (who is also well known in the community). As always, these are suggestions based on my model and my own experience and intended to be review by a knowledgeable professional before implementing.

Person Symptoms

“My story is similar to yours, including an eventual Lyme diagnosis, but antibiotics only helped somewhat. I still have chronic fatigue, inability to exercise, and pain. My biggest complaints are neurological. My brain fog is so intense most days, I haven’t worked steadily in years. I used to be a full time writer and internet consultant, even doing some light programming. Now everything is like Greek to me.

What’s interesting is that my sickness started with IBD and a Chron’s diagnosis, but both were later deemed false after tons of testing. Around 2003 I lost 40 pounds and couldn’t eat anything without diarrhea and extreme pain and nausea. But all of my gastro symptoms were healed by diet, some short rounds of antibiotics and pancreatic enzymes. I haven’t had GI complaints in ages, almost eight years now of almost perfect GI health. Every other symptom has been on a gradual decline leaving me pretty disabled, especially in the brain functioning area.”

Initial Comments

I know people who had a CFS diagnosis, treatment and then ended up with “atypical Crohn’s Disease”, complete with fistulas.  My belief is that we are talking often about a microbiome dysfunction that evolves over time with the population in the gut determining symptoms, etc.  The symptoms are likely determined by the specific strains of species which is well beyond current medical knowledge — but with further improvements of microbiome testing and Big Data analysis could be realized within 10 years if well funded.  Ten years is tooooo long to wait for me (and others), so we have to go back to old school approach and infer and do the best that we can given limited knowledge and even more limited treatment options.

Test Results

  • Lab: Doctor’s Data (same lab as the prior review)
  • Expected/Beneficial flora
    • 4+ Bacteroides fragilis group
    • 3+ Bifidobacterium spp.
    • 3+ Escherichia coli
    • 1+ Lactobacillus spp.
    • 1+ Enterococcus spp.
    • 3+ Clostridium spp.
  • Commensal Flora
    • 1+ Alpha hemolytic strep
  • Normal flora
  • Secretory IgA – borderline low

First thoughts

This is not the typical CFS shift.

Our own friend after antibiotics: Clostridum

This seems to be best ascribed as a side-effect of antibiotics. First thought is Prescript Assist  (no studies, but some MD’s appear to believe it helps).  There are no clear results on the effectiveness “the authors of this study chose to omit any trials involving the use of probiotics for the prevention or treatment of CDI.”[2014] Other choices are:

Bacteroides Fragilis

This species has been associated with neurological changes:

Bifidobacterium longum BB536 appears to reduce the bad ones, this is the species available in Japan.

In terms of herbs:

Suggestion based on my own experience with Cognitive Issues

When I was starting to suffer loss of cognitive issues, I hit the fibrinolytic and anti-hypercoagulation supplements hard, and that kept me working for several months. When I stopped them, the cognitive collapse was quick and severe. I stopped because I was starting to bruise very easily.  My belief is that the coagulation was cause by gut bacteria. I seem totally free of coagulation issue today.

During the recovery, there was a dramatic improvement over two weeks of cognitive issues from taking Haritaki,  Neem and Tulsi. One of the studies I found indicated that some of these was used by traditional Indian medicine men (tribals) for cognitive issues with their patients — so I speculate that it is effective against some of the bacteria causing cognitive issues.

I’m going to run on the herb – cognitive issue tangent here.

Web References:

My general impression is that the following herbs should be tried (one per week, working up to 6 “00” capsules per day if tolerated), noting any cognitive or mode changes from each (if you have a significant other — ask them to record their observations and not report to you until you are done.

  • Haritaki
  • Neem
  • Tulsi
  • Ashwangandha
  • Rosavin
  • JuJu
  • Magnolia Bark

All of them appear to impact bacteria that alter mode or cognitive functions. I have noticed that some probiotics can also alter mood on occasion — however, since we are dealing with overgrowth — I believe the use of herbs may be a wiser course.

Once the cycle has been done — you may wish to cycle with the ones that had the most desired impact.

 

As always, review with your medical professionals, take detail notes, and best wishes on whatever experiments you proceed with.

Unknown's avatar lassesen 2:46 pm on May 20, 2014  

Probiotics and Histamines

I have been seeing some friends improve significantly from lowering histamine levels.

The question arises, which probiotics/bacteria increase or lower histamine levels?

Histamine release are part of the herx effect and thus reducing the level may reduce the severity of herx.

This list may be important for those that are probiotic sensitive and/or salicylates sensitive — the reason for these sensitivity could be the histamine dimension (speculation). There are some DNA association reported between salicylates and histamines sensitivities.

In some cases, it appears that one strain increases histamines and a different strain decreases histamine (i.e. Lactobacillus casei)

  • Increases
    •  Lactobacillus casei [2011]
    • Lactobacillus delbrueckii subsp. bulgaricus [2011]
    • Lactobacillus reuteri [2014] [2013] [2012]
    • Bacillus licheniformis A7 [2013]
    • Bacillus coagulans SL5 [2013]
    •  Morganella morganii [2013]
    • Pseudomonas aeruginosa[2012]
    •  Citrobacter koseri [2012]
    • Enterobacter spp [2012]
  • No Impact
    • Lactobacillus acidophilus [2011]
    • Lactobacillus lactis subsp. lactis [2011] 
    • Lactococcus lactis subsp. lactis [2011]
    • Lactobacillus plantarum [2011]
    • Lactobacillus sakei CRL1862 [2012]
    •  Lactobacillus plantarum Tensia[2012]
  • Decreases
    • Bacteroides thetaiotaomicron [1999]
    • Bacteroides fragilis [1999]
    • Bifidobacterium adolescentis  [1999]
    • Escherichia coli  [1999]
    • Bifidobacterium infantis [2008]
    • Bifidobacterium longum [2008]
    •  Lactobacillus rhamnosus (L. rhamnosus) GG (LGG(®) [2011]
    •  L. rhamnosus Lc705 (Lc705) [2011]
    • Propionibacterium freudenreichii ssp. shermanii JS (PJS)  [2011]
    • Bifidobacterium animalis ssp. lactis Bb12 (Bb12) [2011]
    •  Lactobacillus casei [2012]
    • Lactobacillus plantarum K-1 [2011]
Unknown's avatar lassesen 1:59 pm on May 19, 2014  

Microbiome: Doctor’s Data Lab Analysis 2014-05-19

A reader sent me a copy of a lab report and ask me for comments to discuss with their MD (who is a well known CFS MD) and asked me to directly email this post to their office on the reader’s behalf.

Lab: Doctors Data Inc. Comprehensive Stool Analysis / Parasitology x3

Initial Observations (on the report – not the contents)

  • Citations used were: 1982, 1986, 1988, 1990(3), 1991, 1994(2), 1995(2), 1996, 1997(2), 2001, 2004(2), 2005(2), 2006
    • It feels like the report was  created around 1997, and partially update in 2006 (8 years ago)
    • IMHO, if there are no citations from the last 3 years, the current literature should always be reviewed

Results

I will focus only on the abnormal results in the report:

  • Postive bacterias:
    • 3+ Bacteroides fragilis group
    • NG Bifidobacterium spp.
    • NG Escherichia coli
    • 3+ Lactobacillus spp.
    • 1+ Enterococcus spp.
    • 4+ Clostridium spp.
  • Negative Bacteria
    • 1+ Alpha hemolytic strep
    • 2+ Gamma hemolytic strep
    •  2+ Hemolytic Escherichia coli
    • 1+ Klebsiella pneumoniae ssp pneumoniae
  •  Dysbiotic flora
    • Nothing listed

Comment:

The No Growth (NG) for Escherichia Coli (good ones) and Bifidobacterium is as expected as agrees with prior reports of CFS Microbiome. The high Enterococcus also matches the typical pattern.  The other ones are interesting, especially the high Lactobacillus – this is opposite to that reported in the literature.

I checked with the reader in case they were taking lactobacillus probiotics when the test was done, the answer was none. Mystery.

The Clostridium overgrowth is sometimes seen as a consequence of taking antibiotics — I checked with the reader in case they had taken antibiotics in the prior 6 months, the answer was for prescription:  co-amoxiclav, metrodanizole, minocycline, lymecycline and for herbals  olive leaf extract, high-dose garlic and coconut oil (which is similar to monolaurin).

The absence of any dysbiotic flora would cause many MDs to say “no problem there” – in deed there are no acute problems. CFS is a chronic problem. <soapbox> This is a familiar refrain with CFS, MDs look for acute issues (which are relatively easy to treat), and elect to do no action for non-acute issues. </soapbox>

We have bad E.Coli, Klebsiella overgrowth — which matches the reported pattern for CFS patients reported from Australia.

Unresolved Questions

In general, lactobacillus are known to kill E.Coli so the high hemolytic E.Coli and high lactobacillus seems contrary to simple logic. Stepping away and remembering that within every family there are good and bad ones (including a few species of lactobacillus that are known to fatal). That is more speculative then I prefer.

In reviewing the literature, I found a few gems:

“ The results showed that aqueous extractions of garlic and black peppercorns significantly enhanced the growth of one strain of probiotic bacteria (L. reuteri) whilst inhibiting both pathogenic strains of E. coli at a 1:50 dilution… Both aqueous and organic extractions of ginger significantly inhibited the growth of one or both E. coli strains, respectively (also at the 1:50 dilution).” [2009]

Enhanced viability of Lactobacillus reuteri for probiotics production in mixed solid-state fermentation in the presence of Bacillus subtilis.[2014]

 Lactobacillus reuteri has been linked to obesity and weight gain in children affected with Kwashiorkor using ready-to-use therapeutic food. In contrast, Escherichia coli has been linked with the absence of obesity. Both of these bacteria are resistant to vancomycin [2013] – which may indicate why some CFS become fat and cannot loose weight and other thin and cannot put on weight.

 Moreover, L. reuteri exhibited a strong ability to aggregate with E. coli, which could be another limiting factor of pathogen invasion. [2012]

This suggests that we are seeing up regulation of L.Reuteri due to the high-dose garlic. I asked the reader if they knew their current B-12 levels (which is usually produced by L.Reuteri) as a proxy for species analysis of the lactobacillus (which would have been the next step in digging into this question. The reader responded with no recent tests but results have been very high (suggestive of L.Reuteri “overgrowth”) and very low (suggestive of low levels of L.Reuteri). Being an optimist, I am going to assume that this is L.Reuteri overgrowth and not concerned about it.

As a side effect of this research, I see that R.Reuteri should be taken with Bacillus subtilis and garlic – a little gem of knowledge! On a personal note, my wife often complains about my garlic breath — because I have a preference for food with garlic (I just feel better eating such and if I don’t have some, I can “feel it”, I now have a feasible explanation for my preference!)

Treatment Considerations

This is relatively simple (and is close to what I did for my last remission— I did not have labs, I just assumed that my pattern matched that reported for CFS patients from Australia).

  1. The spice Haritaki works against Klebsiella, Enterococcus and E.Coli (and as many other anti-E.Coli herbs that you can find, see the Crohn’s Herb list). Intent is to NUKE the bad E.coli before introducing Mutaflor (E.Coli Nissle 1917).  For haritaki, work up to 6 gm/day. Expect nasty herx.
    1. Rotating the herbs is recommended. Continuous use of the same herb does result in herb-resistance according to some studies from China.
    2. Add EDTA to breakup biofilms (most of the overgrowths use biofilms) — expect more herx. NAC is a histamine producer and thus you may get a worst herx then with EDTA.
    3. Since herx is usually histamine related, supplement with the following to moderate the herx (these are histamine reducers):
      1. Mangosteen
      2. Diamine Oxidase Enzyme (DAOSin, Histame)
  2. Supplement with as many species of just Bifidobacterium probiotics as you can find at the same time.  Most of the above herbs have minimal impact on this species (at least that is my memory). So taking with 1. above is fine.
  3. Once the herxing stops, then continue for one more week and stop the herbs — wait 2 days and then start with Mutaflor (E.Coli Nissle 1917) as well as d-ribose to feed to it. You may have a significant headache from it — so start with a low dose and work up slowly.
    1. Grape seed extract and/or aspirin seems to work for the headache for some people
  4. Minocycline is compatible with E.Coli Nissle 1917, and is likely a good choice to take with it. Take Prescript Assist with it.
  5. Once you are up to 3 capsule of mutaflor a day without herx or other noticeable effect, go one more week and stop it. You should now be rotating this with the next set of herbs on a regular schedule (i.e. Pulsing as per Dr. Jadin’s protocol)
  6. Switch to Neem and Tulsi as your herbs (appear compatible with E.Coli and effective against Klebsiella and Enterococcus according to PubMed. Again, 6-8 gms/day of each is the target dosage. Again, wait until the herx stops. You may wish to cycle back to 5. a few times before going on to 6.
  7. Rotate weekly across all of the non-lactobacillus bacteria probiotics that you can obtain(with L.Reuteri being the exception). That is 1 week on each and then change to the next.  If you can obtain oral probiotics, then take those concurrently on some weeks (especially if you have a water pick or other deep teeth cleaning device to use first).

Blastocystis hominis

Two of three samples had many (high)  Blastocystis hominis. This reading is controversial in the literature. To quote CDC, “Blastocystis is a common microscopic organism that inhabits the intestine and is found throughout the world. A full understanding of the biology of Blastocystis and its relationship to other organisms is not clear, but is an active area of research.”

Secretory IgA*

This was High. My general belief is that this is caused by the dysfunction bacteria mixture. There appears to be a relationship to bacteroides fragilis which is a reported overgrowth above and IgA. On the good news side — we know something to help both due to a recent article.

“the administration of B. longum CECT 7347 reduced the numbers of the Bacteroides fragilis group (P= 0·020) and the content of sIgA in stools (P= 0·011) ” [2014]

I was unable to find any spices or herbs effective against bacteroides fragilis, so load up on Bifidobacterium longum!  This specific species may be available in Spain (researchers were based there).  A commercial version appears to be in profess (see this 2012 filing) and will likely be produced by Farma-Biotech. If you cannot get this species, any species of Bifidobacterium longum is better than none. 

 

FLASH: longum CECT 7347 is being commercialised by CAPSA and the name of the product in Proceliac.

http://www.centrallecheraasturiana.es/proceliac/

As always, everyone is different and other factors can come into play.

Unknown's avatar lassesen 7:16 pm on May 18, 2014  

An example of a gotcha for studies…

Often studies are done with a “naive” thinking (if you don’t have a good statistician involved with the design – the study may become useless and a waste of time and money and worst mislead the reader!).

Recently a reader forwarded this article to me:

Increased proportions of Bifidobacterium and the Lactobacillus group and loss of butyrate-producing bacteria in inflammatory bowel disease. 2014

My initial take was “perfect” — I have been preaching about the potential negative effect of taking lactobacillus for CFS (with only CFS having a true rationale).

” In conclusion, Bifidobacterium and the Lactobacillus group were increased in active IBD patients and should be used more cautiously as probiotics during the active phase of IBD. Butyrate-producing bacteria might be important to gut homeostasis.”

The problem that is not apparent from the article is a simple one, active IBD patients are very likely to be supplementing with both lcatobacillus and bifidobacterium!!!!(See [2012]) So, a higher count may not be reflecting the actual “natural” state of IBD patients. The lower butyrate-producing bacteria rate is valid because there are no such probiotics on the market in the study area (China).

This is often an ongoing challenge with CFS studies — patients supplements will alter their lab results (I know very well — what do you mean you have hyper-coagulation! your results are normal … But have you looked at the handfuls of anticoagulants that I have in my daily supplement list? )

 

Unknown's avatar lassesen 12:18 am on May 18, 2014  

The possible role of Butyricicoccus bacteria is various conditions

IBS is co-morbid (70-85%) with Chronic Fatigue Syndrome and often become other forms of inflammatory bowel disease (IBD) over time.

“Patients with inflammatory bowel disease have lower numbers of Butyricicoccus bacteria in their stools. Administration of B pullicaecorum attenuates TNBS-induced colitis in rats and supernatant of B pullicaecorum cultures strengthens the epithelial barrier function by increasing the TER.” [2013]

This species of bacteria is named because it produces butyric acid.  This acid is significant:

“Several recent studies have identified butyric acid as a potential therapeutic agent for IBD. Some gut bacteria produce butyric acid naturally in the intestines, but in IBD patients some of these strains are heavily depleted. Trials in mice have shown that injecting one such strain Faecalibacterium prausnitzii into the digestive tract is effective at restoring normal levels of gut bacteria and treating the symptoms of IBD. In addition, novel identified butyrate-producing strains, such as Butyricicoccus pullicaecorum, have been shown to exert similar effects.” [2010]

This leads logically into two directions:

  • Bacteria that produces butyric acid
  • Supplementing with butyric acid

Bacteria producing butyric acid

The species cited above is just one bacteria (which does not appear to be available as a commercial product at the moment). There appear to be a group working on producing Butyricicoccus pullicaecorum as a probiotic according to this presentation and a related patent application assigned to the University of Gent, Belgium (any Belgium readers may wish to make some phone calls… )

The known species producing butyric acid are:

  • Faecalibacterium prausnitzii ( low in IBD [2014], [2014]
    • ” this bacterium is highly oxygen-senstive, making it notoriously difficult to cultivate and preserve”[2014]
    • “cysteine can facilitate the survival of F. prausnitzii upon exposure to air,” – unknown if cysteine supplements would help it grow.
  • Butyricicoccus pullicaecorum

  • Roseburia hominis [2013], first identified in [2006]

  • Clostridium butyricum [2000] [1990] [1990] – is easily available in Japan. An application to sell it in the UK was made in 2012. It is available OTC in Japan (so if you have friend going there — tell them what you want to have brought back!). None of the online shops that I could find will ship to the US (Amazon.co.jp lists it – but will not ship it).
    • Summary of studies here.

Butyric Acid Supplements

This is available as a supplement (GABA), for example on Amazon. There are many articles proposing it for treatment of FM, CFS, etc. for example, this article. Another form, sodium butyrate,  is also available as a supplement and a 2011 study found

“In conclusion, our results show that oral administration of sodium butyrate improves mucosa lesion and attenuates the inflammatory profile of intestinal mucosa, local draining lymph nodes and Peyer’s patches of DSS-induced UC. Our results also highlight the potential use of butyrate supplements as adjuvant in UC treatment.”