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.

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:

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)

• Emtricitabine
• Naproxen – Pain
• Atenolol – High Blood Pressure

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.

Early this year I shouted EUREKA — I found it in greek. I used non-parametric statistical methods and found strong association between certain mixtures of bacteria. How strong? Statistically the chance of some happening by chance was 0.00005%. Many medical studies are published with the chance being 5%.

Over the weekend, someone asked if I could give suggestions for probiotics for mast cell issues. She had no microbiome results. While I was solving some of the site issues, I realized that I could give suggestions with good confidence that they would fit — in fact, may produce better suggestions than a microbiome sample. Why? Noise – often we have 600 bacteria/taxonomy is a microbiome sample and the nasty problem is what to focus on. This is compounded by a lack of research papers on the human impact on many of the bacteria.

Using symptoms only, we have a small subset that are likely the ones misbehaving. These are not bad bacteria, just bacteria that are too abundant or sparse. We want to inhibit or encourage them — not eliminate them.

If you go to the Very Strong Bacteris to Symptom Association page, you will see a list of around 150 symptoms. Some symptoms are missing because not enough people with those symptoms have upload a microbiome and provide their symptoms — for example, Epilepsy has just one. The threshold is 16 samples with the same symptom.

All that you need to do is:

• Check the symptoms that you have.
• Select at the top what type of modifiers that you are interested in
• Click get suggestions for Symptoms Selected.

To answer the question asked about probiotics for histamine issues we see just one recommendation with no known downside. We have others that have a little risk.

A Video walk thru

Bottom Line

All of this material is theoretical produced by using an Artificial Intelligence Engine and have not be validated by clinical studies. These are suggestions. Before doing any of these, have them reviewed by a qualified medical professional familiar with your medical condition.

Back in 1999-2002 period, a chap called Dave Williams (Cap’n Dave) advocated some specific treatments to help CFS patients. He was active on the old Yahoo group that I was a co-moderator on, https://groups.yahoo.com/neo/groups/CFSFMExperimental I ended up incorporating his suggestions into my treatment regimen then. He arranged bulk purchase of supplements (L-Glutamine, CoQ10, Spezzatina (Licorice) etc. and send them free to people that made donations to his ocean health charity (SeaQuake) at that time.

Like me, he ended up successfully treating himself and also has a Master of Science which tends to bring with it a systematic approach to this illness. He has moved on with his life, but I thought a shout out of thanks was due!

With all of the microbiome research, his suggestions are in good agreement (for a significant subset). Today the lists of issues to address will be much longer than his summary in 2000.

You fail to understand that NO SINGLE TREATMENT will ever get fantastic results when used on a PWC! The single therapy approach is doomed to failure because CFS is a multiple problem caused by many months or years of hyperimmunity! People that say they have sudden onset CFS simply do not realize that they were sick for along time and never recovered. The illness they associate with the start of their CFS was
simply the straw the broke the camel’s back. If you want to recover
from CFS you must address hyperimmunity, poor red cell health,
hypoadrenalism, hypothyroid, hypoglycemia, poor NK cell activity, and
multiple nutrient depletion. And, you must address all these factors
at the same time—otherwise your recovery will be limited.

Dave Williams, 2000

What was unknown (not possible to test even!) was the microbiome aspect which links many of these to specific microbiome shifts. So each shift needs to be addressed. Some examples:

• Immune Manifestations: Constipation , Taxonomy Matches: 20
• Comorbid: Hypothyroidism , Taxonomy Matches: 11
• Comorbid: Histamine or Mast Cell issues , Taxonomy Matches: 18
• Neurocognitive: Brain Fog , Taxonomy Matches: 29
• Neurological-Sleep: Night Sweats , Taxonomy Matches: 9
• Neurological-Audio: Tinnitus (ringing in ear) , Taxonomy Matches: 8
• Post-exertional malaise: Worsening of symptoms after mild physical activity , Taxonomy Matches: 17

So I raise a glass of Rum to old Cap’n Dave in thanks!

Today the option to download as JSON or CSV disappeared from the uBiome site. The ability to download the raw sequence data was there.

Over the last 30 minutes, I processed one of my samples via https://metagenomics.sequentiabiotech.com/ . (Which offers free accounts – up to 2 GB of data, the download files from uBiome uploaded is just 12 Megs, so the free account will work for most people.)

The main thing is for people not to go into a panic. It appears that uBiome is planning to add back the download options. If they do not, there are possible alternative solutions.

It generates many files, for example below are some of the files sample. uBiome does 4 passes, and the numbers from each pass is shown below. How you boil the four numbers into one is an art – arithmetic mean, median, geometric mean, etc are possible choices.

I look at my ubiome JSON file for the same data and I get:

• Bacteroides acidifaciens 30655
• Bacteroides faecis 38174
• Bacteroides finegoldii 21914
• Bacteroides ovatus 192887
• Bacteroides sp. J1511 91
• Bacteroides sp. ‘Smarlab BioMol-2301151’ 30
• Bacteroides thetaiotaomicron 153659
• Bacteroides vulgatus 30

This is not surprising, because the raw data fragments are looked up in different reference databases. By the way, there was no E.Coli listed here either!

Bottom Line

I will do a walk thru video this coming weekend for people interested in exploring a different analysis of the raw data. It is a multiple step process that takes about 30 minutes per sample.

Since the flare has gone on for 6 months, I have changed the title to relapse.

• Report #1
• Report #2
• Report #3
• Report #4
• Report #5
• Report #6

I should also mention that immediately after I took this sample, I altered supplements dramatically because ‘something felt like it was going in the wrong direction’. This lab results confirmed it when I look at Diversity by Taxonomy Rank, a 43% jump!

Why is diversity important to monitor? Don’t you want high diversity? To me, the answer is no and appears to be backed up with this study on humans. “Increased Diversity due to increased abundance of less dominant taxa [as a result of stress]“[2017]. Since stress has always been the trigger, the increase of diversity should be a warning sign. More bacteria types means alterations of metabolites and chemical system — dysruption of a well operating microbiome. More is not better always.

A healthy gut ecosystem is rich in diverse species.^[1][2]

Ubiome.com — I believe this is an over simplification

What Did I Change

I went over to my heavy duty kill evil bacteria supplements, namely significant dosages of:

• Tulsi
• Haritaki
• Neem
• Triphala
• Wormwood
• Olive Leaf
• EDTA and NAC as biofilm breakers

Also because of a high blood pressure reading (predictable from microbiome) from an urgent care visit. I also added in (see this post for why):

• Melatonin
• Grape Seed Extract /Resveratrol
• CoQ10
• Fisetin
• Lycopene
• Pomegranate Extract
• Piracetam
• Nattokinease

The results were good:

• Went from struggling to get to 6000 steps per day to over 10,000 steps on many days
• Smart watch blood pressure readings dropped by at least 7mm

Ubiome Reports

Remember this reflects what was happening when I felt something was going the wrong direction and altered supplements etc. My gut feeling appear to have been very correct.

Vitamin K2 and B9 also reported as < 0.05 of selected samples.

Microbiome Prescription Site

First, it’s the charts of uBiome Predicted Metabolic Functions, scanning for interesting things – there are a lot…

A bunch of items to digest.

Condition Templates

Alzheimer’s Mimic

Back in 2012, I had a SPECT scan that was read as mild or early Alzheimer’s disease. I believed that this was caused by a microbiome shift. With the templates and samples, it appears to be confirmed. My microbiome has shifted to match that seen in Alzheimer’s. I am not explicitly concerned because I am working on restoring the microbiome.

High Blood Pressure

A recent urgent care had the physician concerned about my having high blood pressure. A little checking up found that some items that I was taking are known to include blood pressure (which I stopped), and then looked at my microbiome — as it appears that the root cause was the microbiome shift.

Changes in Suggestions

There was no striking difference in suggestions. That is not totally unexpected — the increase in biodiversity was likely in the minor or elusive bacteria. There is little literature on those. 😦

Ubiome reports 5 very elusive bacteria and 10 under 7.5% in the latest sample. The prior has ZERO elusive bacteria and only 2 under 7.5%. The one before has 1 elusive and 3 under 7.5 which was the patten back until 4-09-2019 (2nd and 3rd samples after relapse) when we also had 5 elusive and 10 under 7.5.

Bottom line: The goal is to suppress these elusive bacteria and reduce diversity. Looking over suggestions, I see that I may wish to also add:

• Rhubarb
• Oregano

One item that I became lazy about in the weeks before the last sample was having Barley Porridge every morning. It is high on the list and is the only change that I can identify. It was time consuming to prepared and I felt well enough that I thought that I could skip it — classic ME/CFS mistake.

The next analysis may be very interesting.