Microbiome Shifts Reduces Symptoms in ME/CFS

The 2018 study, “Open-label pilot for treatment targeting gut dysbiosis in myalgic encephalomyelitis/chronic fatigue syndrome: neuropsychological symptoms and sex comparisons.” reports symptoms improvements with increases and decreases of certain bacteria associated with ME/CFS.

A reader asks me to do a recap of what the known shifts are, and thus what you wish to try to correct (and not inadvertently increase by the wrong supplements, probiotics or diet choices).

In terms of published studies, I have assembled a dynamic list on my website (not verified and subject to data entry errors) shown below for genus level and above. When an item is repeated on multiple lines, this means that we have multiple studies report it. H-High, L- Low, B- High or Low (outside of normal)

It is unlikely that every ME/CFS will have all of these shifts. Most will have some.

At the Strain Level, we also have a long list,

Remember, for Low, it is not uncommon for people to have none of these and be perfectly healthy. The Low count is from the average of the group in the study and not definitive for any individual.

Using the citizen science aspect of my site, we do not have a information based on physician verification of precise clinical definition but solely on self-reporting of symptoms. If click on one of the above, say Bifidobacterium, we see two things listed:

  • Citizen Science discoveries dealing with symptoms.
  • Published studies listing conditions that may have the same shift (thus, potential conditions that ME/CFS may evolve to).

For 1 (EBV),2 (MCS), 4(Female), 5, 6 (Post exertional malaise) are in the list of items that are used for a ME/CFS diagnosis

Going over to Faecalibacterium (3 citations) – another LOW one, we see a more massive symptom list, many many are in the classic ME/CFS diagnosis list.

Doing another one, Streptococcus – a HIGH one for a change (3 citations – 2 high and 1 low), we see

Double Validation

One list of bacteria comes from studies on patients that conform to strict definitions of ME/CFS. The other list of bacteria comes out of the symptoms people self-report and their 16s microbiome results. We have a very strong agreement with the results coming from two independent approaches.

What does this mean?

It means that altering the microbiome will improve symptoms (as indicated in the study cited at the start; and in personal agreement with my own experience and many of my readers).

The next step is to determine which of these long lists of bacteria is involved with your ME/CFS/IBS etc. The old conventional tests only does a few of the bacteria — and do not cover all of those reported in studies. By old conventional tests, I mean:

A 16s report is strongly recommended (choices). Thryve offers the best “bang” (most taxa reported – 500-1200 different bacteria often) for the cost ($ < $100). Many 16s tests are sold direct to consumers and do not require going thru a physician (Just like DNA tests, for example 23andMe).

Once you know the bacteria involved, you need to know how to change them. If your physician, nutritionist or other health professional are well skilled and read on the microbiome, they should be able to guide you.

If they are not, I have created my free analysis and suggestion artificial intelligence engine http://microbiomeprescription.azurewebsites.net/ which uses over 95,000 medical facts on the microbiome. You must review those suggestions with your medical profession because some may be inappropriate given other medical conditions.

Candida – What Studies Find

The Candida species play a role in a healthy body. It is when there is too many that problems start. A friend asked me to put together what we know based on published studies only, no urban-medical-beliefs.

  • There is an increased total fungal load particularly of Candida and Malassezia species in the faeces and mucosa of Crohn’s disease patients, and a lower fungal diversity in the faeces of ulcerative colitis patients. [2019]

Herbs

Antifungal efficacy of herbs (2019). The larger the numbers above, the more effective it is

So to translate into familiar terms, in decreasing effectiveness:

  • Garlic vine ( Echinophora platybola )
  • Benth ( Pogostemon parviflorus )
  • Ashwagandha (Withania somnifera) – Easy to get
  • Turmeric (Curcuma longa) – Easy to get
  • Asthma-plant (Ayurveda- Euphorbia hirta )
  • Ginger (Zingiber officinale )
  • Henna ( Lawsonia inermis )
  • Swertia ( Ayurveda – Swertia chirata )

These are cited, with further studies on this page (in french) and includes the above with links to multiple additional studies for each.

Other Stuff

  • ” It can be concluded that monolaurin has a potential antifungal activity against C. albicans and can modulate the pro-inflammatory response of the host. ” [2016]
  • ” The difference between the groups [chlorhexidine, lactobacillus probiotics, coconut oil] was not statistically significant (Chi-square value 7.42, P value 0.06). ” [2016]
  • ” Eucommia ulmoides, Polygonum cuspidatum, Poria cocos and Uncaria rhyncophylla showed activity against both bacterial and fungal strains, indicating their broad spectrum of activity. ” [2013]
  • ” Data show that mustard [i.e. Turmeric] and coconut oil seem to be effective as in these the spore germination was poor. ” 1992
  • Pau D’Arco ( Tabebuia ) – Studies found no significant effect [1994]
    • Tabebuia avellanedae (methanol extract), with MIC varying from 0.06 to 0.001 mg/mL;  ” [2010] – this is a fraction of the effectiveness of items above.

Probiotics

  • Enterococcus Faecalis appears effective [2014] (available as probiotic)
  • Lactobacillus GG, Lactobacillus rhamnosus LC705 and Propionibacterium freudenreichii ssp. shermanii JS was shown to be an effective means of controlling oral Candida and hypo‐salivation in the elderly (Hatakka et al2007). [2016]
  • Bacillus subtilis exhibited clear zones of inhibition for Candida albicans and Candida parapsilosis but not for Candida krusei. [2016]

Sookkhee et al., in 2001, studied the effects on Candida albicans growth of different lactic-acid bacteria isolated from the oral cavity of volunteers and found that two strains, Lactobacillus paracasei and Lactobacillus rhamnosus, had the strongest effect on the yeast [44].
Lactobacillus reuteri is a promising bacterium (especially DSM 17938 and ATCC PTA 5289) for its anti-Candida properties, confirmed by several studies. In one of these, Lactobacillus reuteri was demonstrated to be able to reduce Candida load in vivo through co-aggregation, modification of oral pH with production of lactic acid and other organic acids that inhibit the virulence of Candida cells, and production of H2O2 [45].
In a recent in vitro study by Coman et al. (2014), the strains Lactobacillus rhamnosus IMC 501 and lactobacillus paracasei IMC 502, alone or in combination, showed an inhibitory effect on Candida spp. growth [46].
Lactobacillus delbrueckii ssp. bulgaricus B1 and Lactobacillus delbrueckii ssp. bulgaricus TAB2 were found to fight Candida, releasing high amounts of lactic acid [47].Recently, it was found that Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 modulate Candida glabrata virulence, through the complete inhibition of fungal biofilms [48].In addition, Lactobacillus acidophilus ATCC 4356 was found to inhibit the biofilm formation of fungus through in vitro experiments [49]. Biofilm formation is probably reduced through the production of substances called “bacteriocins” by probiotics. Wannun et al. reported the isolation of a bacteriocin, called “fermencin SD11”, from Lactobacillus fermentum SD11, a human oral Lactobacillus, which has a strong inhibitory effect on oral Candida cells [50].

Effect of Probiotics on Oral Candidiasis: A Systematic Review and Meta-Analysis 2019

Histamine Caution

  • All Lactobacillus Reuteri are histamine producers.
  • Many Bacillus subtilis are histamine producers [2007]

Lactobacillus rhamnosus appears not to be a histamine producer and reduces histamines [2011]

The many shades of Gluten

Or, all gluten is not the same — just like all cheese are not the same. People may have issues with one type of gluten — especially wheat gluten where there was been many generations of genetic manipulations to produce more profitable wheat harvests.

This is of concern to me in dealing with people with microbiome dysfunction – such as Myalgic encephalomyelitis/chronic fatigue syndrome and even fibromyalgia. Popular urban medical myths often preach that all gluten is evil. I very much disagree.

Historically, grains were an important part of our diet — especially less refined grains. Our microbiome tend to do better with grains, especially oats and barley.

Fundamentals

Different cereal crops have different gluten. This may be very important with ancestry from the United Kingdom, Scandinavia, Poland, Russia, Baltic states. Before the genetic manipulation of wheat, there was a “wheat line” across Europe. North of it, wheat did not grow/was not cultivated. Wheat’s gluten was foreign to the microbiomes and DNA of people living there. Wheat has had a massive DNA history with historic Chinese wheat being very different than Spanish where (see this article). Wheat has been massively manipulated over the decades.

  • Gliadins found in wheat, which have three main types: three main types of gliadin (α, γ, and ω). Each has different amino acid sequences.
  • Hordeins found in barley, which have with major grouping B, C, D and γ [2009]
  • Secalins found in rye, which has γ and ω groups [1983]
  • Avenins found in oats (up to 80%)

Several later studies (Srinivasan et al., 1996; Janatuinen et al., 2002; Kemppainen et al., 2007; Guttormsen et al., 2008) indicate that oats are not unsafe for those with Coeliac disease (CD), and thus oats are now often included in the CD diet (Butt et al., 2008; Guttormsen et al., 2008).

Oats Elke K. Arendt, Emanuele Zannini, in Cereal Grains for the Food and Beverage Industries, 2013

Bottom Line

If you “react to gluten” or “feel better without gluten”(which may be an induced placebo effect), there are dozens of different chemicals falling under the gluten label. You should attempt to isolate which ones are problems. Wheat gluten is something that I personally minimize, because all of my ancestors were above the wheat line — dark solid rye bread, rye crispbread were what they had. Wheat flour was an imported luxury. Oat and Barley porridge for breakfast was also traditional.

Image result for rye crisp

Cutting all gluten from your diet is likely very unhealthy to your microbiome. Even if you have Coeliac Disease, you should try barley and oats porridge (beware of buying from “bulk” – cross contamination is very common using bulk bins).

uBiome Aftermath

With the announcement that uBiome is asking to change from a Chapter 11 (Reorganization) to Chapter 7 (Shut the doors!) – the question is what comes next?

During the company’s Chapter 11 filing, the company had indicated that it would be looking into a sale. However, according to the motion it filed in court today, the company wasn’t able to secure lending that would enable it to continue operations. As a consequence, it has requested the court allow it to cease operations and liquidate its assets in order to pay off its creditors. The bankruptcy court still needs to approve the motion. If it is accepted and the company moves to Chapter 7, the liquidation of uBiome’s assets will happen under the supervision of a court-appointed trustee.

Forbes

At this point it becomes interesting — superior technology than what ubiome (also thryve, and American/British Gut) is available. There are two on interest because they are using superior technology

  • SunGenomics.com – they do not have downloads available yet
  • XenoGene – they do have viable downloads available (just uploaded some tonight by data scraping their PDF files) and my contact with them indicates they are going to be making an upload friendly version available soon

What is the difference between technologies…. well with the older technologies we are talking 400-600 taxonomies. The last XenoGene that I uploaded had over 6000 taxonomies – a factor of 10 more! This was 182 pages of data with one taxonomy per line. This does come at a cost 10x more — but I expect the price to come down rapidly. There is a market out there… the fact that it appears that 1.4+ million samples have been processed by uBiome means that opportunity is there, a $140 million dollars of potential sales!

To me, Xenogene has set a new gold standards for retail microbiome reports.

The company that grabs this opportunity, the vacuum left by uBiome may be in China, Russia, Israel, India, Denmark, Australia or Spain. Setting the right price point, picking the right equipment and designing a good friendly user site is the key.

See known alternative providers on this page.

Nature abhors a vacuum! and capitalism abhors missing an opportunity to make money!

Xifaxan and SIBO 👎

A reader wrote today: “One thing that maybe you can comment on. Xifaxan did not show up and is the new standard for SIBO treatment. Any insight? “

I am going to do a walk through of how those of you without brain fog could do it. [Hint: I do not want to have hundreds of request to do it for other things – this reader got lucky with asking the right new question!]

First we need to decipher the trade name Xifaxan

XIFAXAN tablets contain rifaximin, a non-aminoglycoside semi-synthetic, nonsystemic antibiotic derived from rifamycin SV. Rifaximin is a structural analog of rifampin. The chemical name for rifaximin is (2 S,16 Z,18 E,20 S,21 S,22 R,23 R,24 R,25 S,26 S,27 S,28 E)-5,6,21,23,25-pentahydroxy-27- methoxy-2,4,11,16,20,22,24,26-octamethyl-2,7-(epoxypentadeca-[1,11,13]trienimino)benzofuro[4,5- e]pyrido[1,2-á]-benzimidazole-1,15(2 H)-dione,25-acetate. The empirical formula is C43H51N3O11 and its molecular weight is 785.9. 

rxlist.com

The next thing is to see if we have any information on these two – for xifaxan we have none, for rifaximin, we find it on our full list of gut modifiers that we have some information on. It’s link is here.

The second side of the question is microbiome shift for SIBO. We have two extremely high associations (in yellow) and a ton of associations < 0.05 (5% chance of happening at random — almost all at the high end!). I am extremely conservative in declaring significance.

SIBO Statistical Analysis

The next step is easy: comparing the two lists and seeing where there “is apparent agreement”, that is, xifaxan reduces a high bacteria (or encourage a low one).

  • For the Eggerthella and Eisenbergia genus — there appears to be no impact.
    • Similarly no impact for Moryella, Flavonifractor, Dielma, , Sarcina
    • In terms of parents of species: Nothing on Gordonibacter,Prevotella, Anaerosporobacter
  • It does decrease Bacteroides
  • It does decrease the parent of: Blautia

Where do we get this information?

The key information is summarized on the above page (with links to the source — definitely open medicine!), but to illustrate for the casual reader:

  • Review article: the antimicrobial effects of rifaximin on the gut microbiota. Alimentary pharmacology & therapeutics (Aliment Pharmacol Ther ) Vol: 43 Suppl 1 Issue Pages: 3-10 PubDuPont HL : 2016 Jan Epub
  • Modulation of the gut microbiota composition by rifaximin in non-constipated irritable bowel syndrome patients: a molecular approach Clinical and Experimental Gastroenterology (Clin Exp Gastroenterol ) Vol: 8 Issue Pages: 309-325 Pub: 2015 Dec 4 Epub: 2015 Dec 4

Inference from above

It does not move anything is the wrong direction :-). However, it only impact 18% of the bacteria shifts at the genus level. I would expect that it would result in statistically significant improvement of a study group with enough data massaging. No remissions should be expected.

Would I take it? No, I would first try the following:

from: http://microbiomeprescription.azurewebsites.net/data/Suggestions?modifier=B&modifier=H&modifier=I&filterby=order&topcount=20&bottomcount=20&selectby=s&modifier=3&symptomId=126

In fact, doing a little behind the scene magic (by adding modifier=P,A,D to the url), the following may be more effective (and definitely off label)

This latter approach is hunting for drugs based on reported microbiome changes; then evaluating safety and side-effect risks.If you have a condition that could warrant being prescribed them, you may wish to negotiate with your physician on a change of prescription.

Actual Studies?

  • ” Response rates to rifaximin (550 mg three times daily for 14 days) were 47.4% for hydrogen positivity alone and 80% for both hydrogen and methane positivity. ” [2019]
  • ” Rifaximin was not effective in improving IBS symptoms and QOL in GW Veterans with non-constipated IBS. ” [2019]
  • ” Rifaximin therapy is well tolerated and the results are promising in terms of efficacy in eradicating small intestinal bacterial overgrowth in CF. ” [2019] “promising” is double talk for no statistically significant results but we are not willing to give future grant money to do more studies.
  • ” Combination of amoxicillin and rifaximin may be effective in the treatment of patients with small intestinal bacterial overgrowth syndrome and concomitant H. pylori infection. ” [2018] again “may be” means that they did not get statistically significant results.

So, studies appear to support my logical conclusion using the model and our citizen science data.