Comparing Microbiomes around a CFS/ME flare

I recently got this email (with samples uploaded to Microbiome Prescription). I am going to compare these samples to see if I can gain any insight.

Just this morning received the new Thryve results. ***** was in really bad shape when this sample was taken – full crash. For reference he would have been a “5” for the first sample and a “1” or “2” for this one.

First Impressions

The top one was for “5” and bottom for “1”. There was an apparent drop in ‘rare’ bacteria. With “5”, we have 16.3% in the top 16% (i.e. expected) and with “1” we are down to just 5%. This implies some bacteria have become intolerant or bias against others. In the video below, I am going to walk thru my explorations (i.e. playing hide and seek with the cause). The fact that these two samples were taken close to each other means discovery is a lot easier because microbiome drift is greatly reduced.

Do we have genocide happening?

The above leads us to look at natural antibiotics, we see some very dramatic shifts – especially in bacteriocins (a protein produced by bacteria of one strain and active against other strains). As we saw above, the natural “push and shove” between bacteria has been suppressed with lots of bacteria dropping off the radar.

Hydrogen peroxide is another known bacteria killer, it too had a similar increase of amount

By clicking on the numbers, we can see the bacteria responsible — for example, Hydrogen Peroxide, we see that it’s main producer is Lactobacillus where we went from double the upper normal range to triple the upper normal range .

We can do this for the others (see video for a walk thru). The biggest impact at a genus, was Blautia  (from 64%ile to 93%ile)

We see that Lactobacillus is sitting at the 90th %ile with “1” and was at the 86%ile with the “5”. Almost all of the Lactobacillus is Lactobacillus rogosae. Here was have a catch — it is not a lactic acid producer but one of the greatest hydrogen peroxide (H2O2) producer! it was also high in “5” but much less.

Keeping Focus on the recent change and not the long term condition

There was some shifts that were surprising — for example KEGG computed supplements decreased with the “1” sample. Probiotic suggestions were similarly reduced with less weight.

“5” sample“1” Sample
beta-alanine
D-Ribose
Glycine
iron
L-asparagine
L-Cysteine
L-glutamine
L-Lysine
L-Phenylalanine
L-Proline
Molybdenum
NADH
Phytase (Enzyme)
L-Phenylalanine
Molybdenum

Using the Krona Charts, we see the overall shift well. First the “5” sample

Then the “1” sample, notice that the green area took a major decrease.

With the Krona Charts, we can drill down by just double clicking. Below are the drill downs on Clostridia , again “5” first and then “1”. Drilling down allows us to see how the composition of a group changed.

The main item was an increase of Blautia, especially Blautia wexlerae (91%ile to 98%ile) and Blautia faecis (63%ile to 92%ile). Most of the Blautia species increased — resulting in a lot of bacteriocins being produced.

Suggestions

Because Blautia and Lactobacillus appears to be a major players, we hand picked for them:

The suggestions were no lactobacillus probiotics (obvious)

tea0.361
  glycyrrhizic acid (licorice)0.306
  licorice0.306
  saccharin0.278
  salt (sodium chloride)0.278
  cranberry (flour, polyphenols)0.222

I am not too happy with these, because of the dominant item, Lactobacillus rogosae , having no known modifiers, so the items are generic lactobacillus modifiers — which may or may not apply. I went back and just picked the high blautia.

In the suggestions, we have a slight dilemma, lactobacillus rhamnosus (probiotics) was a to avoid (TOP of the list to avoid) but a mixture was a to take.   lactobacillus rhamnosus gg,lactobacillus,rhamnosus,propionibacterium freudenreichii,bifidobacterium breve (probiotics) . The logical conclusion is that propionibacterium freudenreichii is a to take. I happen to recall having taken this as a probiotic, single species or eat lots of  Emmental cheese! This is the product Nutricology, Securil, Propio-Fidus-Based. For Licorice, my usual favorite source is not tea or supplements, but Spezzatina which Cap’t’ Dave Williams introduced me to back in the 2000’s on CfsFmExperimental (originally on egroup). He too (like myself) went into remission.

Modifier To Add or increaseConfidence
  licorice1
  glycyrrhizic acid (licorice)1
  resveratrol (grape seed/polyphenols/red wine)0.56
  lactobacillus rhamnosus gg,lactobacillus,rhamnosus,propionibacterium freudenreichii,bif (probiotics)0.483
  lactobacillus rhamnosus gg,lactobacillus,rhamnosus,propionibacterium freudenreichii,bifidobacterium breve (probiotics)0.483
  triphala0.439
Modifier To Remove or DecreaseConfidence
 lactobacillus rhamnosus (probiotics)0.841
 cocoa0.747
 resistant starch0.72
 bifidobacterium longum bb536 (probiotics)0.561
 barley0.56
 lactobacillus plantarum (probiotics)0.56
 Slippery Elm0.527
 vitamin a0.483
 iron (Note that Iron disappeared with KEGG from “5” to “1”0.483

Lactobacillus rogosae – What do we know?

There is painfully little data on it, just five studies. In fact, it is “not available in any established culture collection; therefore, they cannot be included in any scientific study.” [2004] [2014]

  • It is reduced by going to space šŸ™‚ [2021]
  • It is reduced by Methicillin-resistant Staphylococcus aureus  [2017]
  • “The species most frequently related to vaginal health were Lactobacillus jensenii and Lactobacillus rogosae.” [1992] This actually hints at why other bacteria appeared to be suppressed — it is a strong hydrogen peroxide producer.

Some interesting nodes:

  • “. The hydrogen peroxide-producing colonic bacteria have been also suggested as causative agents of IBD in young adults (107).” and “hydrogen peroxide … are dangerous to mucosal cells, easily penetrating through membranes and causing, depending on their concentration, their apoptosis and necrosis[death]”
    • IBS is often comorbid with CFS/ME

Blautia wexlerae – What do we know

We have more data, some fourteen.

  • High in prediabetics [2020]
  • Increases with body mass index (BMI) [2021]

KEGG Data

“Resistance to hydrogen peroxide is proportional to pyruvate oxidase expression.” [2003] This is Enzyme 1.2.3.3 in KEGG – which we can look up! The count increase from 12%ile in “5” to 29%ile in “1” indicating an increase of bacteria that tolerates hydrogen peroxide. The following appear in the new sample that have this enzyme: Weissella ceti, Aerococcus urinae and a doubling of Staphylococcus haemolyticus.

Unfortunately, KEGG data applies only to those that are fully sequenced, so data is incomplete and often is only for one strain of a species.

Bottom Line

We can see the probable cause, increase of L.Rogosae which may have saturated the gut with hydrogen peroxide killing off or reducing many other bacteria. Hydrogen Peroxide tolerant bacteria grew. I was unable to find any explicit information on B. Wexlerae being hydrogen peroxide tolerant. However we do find B. Wexlerae, and Blautia in general are “catalase-negative, indole-negative and produced acetate and succinate as end products of metabolism” [2008]. Since catalase breaks down hydrogen peroxide — it implies that they may be tolerant (at least not consuming).

I should note that Staphylococcus aureus is heavily implicated with ME/CFS and is also catalase-negative [2010]. Also see early post: Staphylococcus aureus ā€“ the CFS maintainer? and A forgotten treatment for fibromyalgia/chronic fatigue syndrome?

The logical way would be to reduce or eliminate L.Rogosae — but we have no information on what effects it which is acceptable (or affordable!). Contrary to general opinion, Hydrogen Peroxide: the body’s best defence system, too much is not desired.

Strategy to reduce the Hydrogen Peroxide

The basic concept is that the environment and other bacteria are symbiotic (a mutually beneficial relationship). If you alter the environment, then the bacteria will change. We want to shift it away from high Hydrogen Peroxide levels and consuming bacteria. We do not know how to alters those identified — but we do know how to break down the Hydrogen Peroxide.

  • Catelase [Wikipedia] breaks down hydrogen peroxide (H2O2) and is available as a supplement. It appears to be the simplest path forward.
    • There have been NO STUDIES of this supplement with ME/CFS. It is a novel approach.
    • It is being investigated for treating IBD [2021]
  • Additional possibilities include: manganese oxide [Src], yeast (contains catelase)[src],  

As a side note: high hydrogen peroxide (H2O2) is associated with loss of hair color. It was during a ME/CFS relapse that I lost most of my color (older brother and both parents retained their hair colors until they were decades older).

Videos

Video walk thru (more details) of this post

Below is the original analysis

and for the walkthru for this post