uBiome of a long time stable CFS patient

 

Patient Summary

– Current age 44

– Main symptoms: Brain fog, fatigue, weakness, exercise intolerance, feel worse after eating, certain weather (high winds or overcast skies) cause me to feel extremely anxious/exhausted. The physical symptoms haven’t changed much since teenage years, but are gradually worsening with age.

– Typically able to work around 10 hours per week, running own company from a zero-gravity chair, but requires significant effort. Brain fog is the major impediment.

– Hypersensitive to chemical fragrances, but equally sensitive to light, sounds, tastes, and touch. No strong Aspergian tendencies, but an INTJ on Myers-Briggs and a 5w4 on the Enneagram.

– Fell from the second floor to the first floor of family home when 18 months old (no resulting broken or fractured bones).

– Non-restorative sleep since age 7, when began waking up sluggish and with a tired-achy-pressure sensation around eyes. The sensation itself is present 24/7 and is still present today. (ENT doctors consistently report I have no sinus problems.) Tended to be constipated.

– Developed chronic gas at age 14

– Chronic fatigue since age 15, with gradual onset and no known infection that preceded the onset of fatigue

– At age 17 undertook an elimination diet and discovered refined sugars caused feeling ill, grains cause bloating, and cultured milk products make eyes burn. Since then I’ve loosely followed a paleo diet.

Earlier this year I tested positive for EBV antibodies, and I vaguely recall this was already true in my late teens, as well.

Recently I’ve tried Symbioflor-2 (concurrent with Symbioflor-1) for a week, and Act’Regen five days now, with no discernible reaction to either.

uBiome results

From the notes above, we have a much higher functioning CFS person than most. The uBiome results suggests that is the case — many items are much less severe than what is often seen in other’s uBiome.

Diversity 88%ile (Common on uBiome results for CFS)

x1

x3– E.Coli’s parent — much higher than most. But Genova Diagnostics lab report Zero for E.Coli specifically.

Bacteriodetes/Firmicutes shift is very moderate compare to other CFS patients

x2

Sleep deprivation (possible Melatonin) families — not too bad, g low firmicutes; melatonin is not suggested

x4

Proposed bacteria genus contributing to MCS: above threshold (0.32x)

x5

Uncommon Bacteria

x6

Overgrowths

x7

Analysis of Overgrowth and Rare Genus

  1. Acholeplasmataceae (family) 
  2. Alloprevotella (genus) 
  3. Anaerotruncus (genus) 
  4. Cronobacter (genus) 
  5. Elusimicrobium (genus) 
  6. Enterorhabdus (genus) 
  7. Erysipelatoclostridium (genus) 
  8. Oscillibacter (genus) 
  9. Pseudobutyrivibrio (genus) 
  10. Terrisporobacter (genus) 
  11. Thalassospira (genus) 
  12. Klebsiella pneumoniae (species)  (From Genova Diagnostics)

NUTRIENTS/ SUBSTRATES

INHIBITED BY

ENHANCED BY

INHIBITS

Despite 11 genus listed, there is little known information on what makes them tick.  Flaxseed porridge with a glass of Pomegranate juice for breakfast is the only clean suggestion.

Elusimicrobium is a new genus to me (a.k.a. Termite Group I),  I have not seen it in other uBiomes. It is both rare and the greatest relative overgrowth. Going over to http://www.genome.jp/  we can discover what antibiotics it may be resistant to (based on it’s DNA):
x9

Digging into PubMed, we find:

  • ” an unusual peptide degradation pathway comprising transamination reactions and leading to the formation of alanine, which is excreted in substantial amounts. ” [2009]
  • “The isolate grows heterotrophically on sugars and ferments D-galactose, D-glucose, D-fructose, D-glucosamine, and N-acetyl-D-glucosamine to acetate, ethanol, hydrogen, and alanine as major products but only if amino acids are present in the medium. ” [2009]
  • “Unexpectedly, Elusimicrobia made up 14% of the operational taxonomic units detected in one subject at day 7, which is the only value that contributes to the Elusimicrobia average abundance of 3% for that date. This may be due to a subject that originated outside of North America with some rarely reported microbiome taxa.” [2017] – in this study, yogurt increased it’s abundance.

Avenues to Explore

These are based on history and labs that were included.

Epstein–Barr virus (EBV)

  • Lactobacillus casei Shirota probiotic (Yakult) – “A similar effect was found for plasma EBV antibody titres in EBV seropositive participants (p < 0.01) with antibody titre falling in the probiotic group but increasing in the placebo group over time.” [2016]

Hypercoagulation

  • See this post, it may account for cognitive, sleep and other issues.

IBS Probiotics

  • See this post and the literature supporting these specific probiotics.

High Triglycerides, Cholesterol

We know that some bacteria increases it (and may be a contributing factor), so looking at those known to lower it (perhaps by taking out the other strains).

Antibiotics for Oscillibacter

The “grains cause bloating,” combined with Oscillibacter being enhanced for Resistant starch Type I, II, III hints that this may  play a significant role.

There is a 2013 study from Denmark treating this genus, the antibiotics tested are shown below. Tigecycline is a tetracycline and metronidazole is a common antibiotics that generally reports good results with CFS patients.

x8

Bottom Line

There was no clear clustering of nutrients or inhibitors in the rare or overgrowth. If iron supplements are being taken, consideration should be done for stopping them (see this post on the bacteria connection for iron, and “Could iron supplement makes CFS recovery harder?

Given the food sensitivities reported, the reader will need to slowly feel out  the best path.

As always, consult with your medical professional before adding probiotics, changing supplements etc.

 

Probiotics Available in Spain

One of the challenges is just getting the probiotics that are likely to help. Often they are unavailable in one country but easily available in another (or if available the price is many times higher!!). Another source of single strains probiotics in the UK.

During my 2nd round of CFS, I ended up working with a Czech CFS patient to get some stuff (Piracetam) that was over the counter there and totally unavailable in the US at that time. She sent me packages and I sent her money (usually 50% more than her cost as a thank you for the effort). This model is something to keep in mind.

A reader in Spain forwarded me the list of those available in Spain — here is my quick review of the interesting ones. Two are unusual and I will research each for a future post.

  Probiótico
Aflorex (cáps)
  • B. infantis 35624TM
  • 1 BCFU/cáps.
Bivos (polvos)
  • L. rhamnosus GG (ATCC53103)
  • 6BCFU/cap
gotas) (Casen)
  • L. reuteri Protectis ((DSM 17938).
  • 0.1 BCFU/cap
Bi-Oral suero
  • L. reuteri.
  • 0.1 BCFU/cap
SHS – Synbiotic
  •  Bifidobacterium longum
Lactanza hereditum (Angelini)
  • Lactobacillus fermentum Lc40 (CECT 5716).
  • 3BCFU/caps.
Muvagyn® probiótico (cap vaginales)
  • L. rhamnosus PB01 (DSM 14870)
  • L. gasseri EB01 (DSM 14869).
  • 100 millones de ufc/cáps.
Kaleidon 60

Kaleidon 30

Kaleidon Hidro

(Menarini)

  •  Lactobacillus rhamnosus GG (ATCC 53103).
  • BCFU/cap
Yobalex (Bayer)
  • Bifidobacterium longun
Symbioran (Ordesa)
  • B. longum subespecie infantis CECT7210,
  • L. rhamnosus
  • L. helveticus),
Lactibiane ATP (Pileje)
  • Lactobacillus rhamnosus
  • LA801. 12BCFU
Probiomax flora intestinal (Aquilea)
  • Lactobacillus paracasei LPC00,
  • Lactobacillus rhamnosus LR04),
  • Fructooligosacáridos.
  • 6.000 millones de ufc.6BCFU
Probiomax defensas (Aquilea)
  • Lactobacillus plantarum LP02,
  • Bifidobacterium lactis BS01,
  • Lactobacillus rhamnosus LR04,
  • Vitamina C, 40 mg, FOS (40 mg).
  • 12BCFU.
I3.1® L. plantarum (CECT 7484 y CECT7485)

P. acidilactici (CECT 7483).

3.000 BCFY

NS Florabiotic Instant (sob). L. rhamnosus GG (ATCC 53103)

5 BCFU

Protransitus® (cap) L. plantarum 299v (LP299vTM)
10 BCFU
Reuteri® gotas L. reuteri Protectis (DSM 17938).

More Before and After Fecal Microbiome Transplants uBiomes

Fecal Microbiome Transplants(FMT) had great promise when the first ones happened — almost immediate remission of CFS symptoms. With time we have discovered that the FMT benefit fades, sometime quickly, sometimes slowly. I fear that it may be a similar problem as blood transfusions and organ transplants — compatibility is needed, but we still do not know how to determine it.

There have been attempts to do high dosage antibiotics prior — which according to reports from readers — have not made significant changes in the pattern.

Patient Summary

History

  • Respiratory tract infections as a child
  • Pneumonia twice as an adult (hospitalised once)
  • Reflux and IBS symptoms on and off through the 2000s
  • In sept 2011 I came down with flu type symptoms may have been ebv. Looking back in retrospect I was overexercising at the time and probably not supporting it nutritionally so there were a number of stress factors contributing. I gradually went down hill. Diagnosed with CFS December 2011.
  • Had a small recovery in 2013 due to lots of relaxation techniques (breathing and mindfulness) strict paleo diet.
  • 2014 started back to work. Things were pretty bad(full blown SIBO symptoms) had bioscreen gut test done (attached) was given emycin.
    • Post emycin[Erythromycin] histamine  symptoms went away and mood/energy improved.
    • 3 months after did a course of flagyl,rifaxmin and nistatin followed by FMT (10 rounds).
    • Improvement for a few months then bronchitis required AB and gut symptoms came back.
  • 4 more rounds of AB combinations of Flagyl, neomycin,cipro and rifaximin.
    • Each time less benefit from the AB each time followed up by FMT.
    • In 2016 stopped work did elemental diet 2 rounds of 14 days.
    • Improvement of gut problems but lots of inflammation symptoms.
    • Things have been very bad since I have tried lots of different herbal protocols in the last 2 years with a limited amount of success.
    • My liver is struggling to process things (based on experimentation and a functional not supported by mainstream medicine test).

Current symptoms:

  • Fatigue is not that bad.
  • Constant cycling of gut symptoms: burning, cramping gas, bloating.
  • I react to many things I eat both foods and supplements but it is inconsistent. Histamine is definitely a problem and I think High salicylate/phenol also seem to be a problem.
  • Inflammation symptoms.
  • Tingling in face hands and feet.
  • Whole body trembling
  • Sharp pains in feet
  • Feeling like head will explode
  • Headaches
  • Mental state: Extreme depression and anxiety

uBiome

Time Line

Phyllum Changes

phy

Genus Changes

gen

Details

1/10/2017 3/07/2017

E.Coli Parent:Enterobacteriales:  < 0.01X
Gordonibacter:   0.04

E.Coli Parent:Enterobacteriales:  < 0.01X
Gordonibacter:   0.08
Diversity: 86%ile Diversity: 86%ile
Unique Bacteria
Unique Bacteria
bf1
B/F Ratio: 4.8x normal
bf2
B/F Ratio: 4x normal
Sleep Deprived Genus
CE1
Sleep Deprived Genus
ce2

Initial Impressions

  • EMycin: Erythromycin belongs to a group of drugs called macrolide antibiotics.  (one of the recommended ones, see this post)
  • cipro – Ciprofloxacin is fluoroquinolone antibiotic (one of the recommended ones, see this post)
  • Rifaximin: Does not reduce Bifidobacteria [2010] [2007] [2002]
  • Neomycin is an  aminoglycoside antibiotics.

I am unhappy to see that Bifidobacteria decreased, and happy to see the histamine issue disappear.

Analysis of Overgrowth on Both uBiome

  1. Akkermansia (genus) 
  2. Alistipes (genus) 
  3. Butyricimonas (genus) 
  4. Desulfovibrio (genus) 
  5. Odoribacter (genus) 
  6. Parabacteroides (genus) 
  7. Phascolarctobacterium (genus) 
  8. Victivallis (genus) 

NUTRIENTS/ SUBSTRATES

ENDPRODUCTS

INHIBITED BY

ENHANCED BY

 

INHIBITS

Analysis

The FMT did not result in positive significant change of the microbiome — same diversity, similar bacteroidetes/firmicutes ratio, etc.

There was one interesting change at the family level was those related to the Melatonin /sleep bacteria went down. Items #3 and #4 are my greatest concern — but all available information on inhibitors is zero.

The only thing common with the nutrients is D-Glucose — a familiar theme in many uBiome studies, dietgrail.com has a helpful table here of foods low or without glucose. There are no common inhibitors 😦 .

One question that arises, does a FMT result in “noise” in the microbiome for N weeks after the FMT — resulting in instability of the microbiome (i.e. is this the cause of an absence of clustering seen above?)

Bottom Line

There was no mention of probiotics in the patient notes. Given the number of rounds of antibiotics I would suggest starting with Prescript Assist and then add in Equilibrium.  The E.Coli probiotics OR Lactobacillus Fermentum ME3 would be the next ones to rotate to.

The reader also supplied results from Genova Diagnostic test done before either of the above.
gut

This would suggest:

  • butyrate supplements
  • Miyarisan (Clostridium butyricum) probiotics

As always, consult with a medical professional before altering diet, changing supplements or probiotics.

 

 

Another uBiome Review with Bifidobacteria Overgrowth

 

This is a report from someone who started trying some of my suggestions in June.

  • Week #1: Prescript Assist just before bed. In morning Vitamin D3 and Licorice
  • Week #2: Add Equilibrium in AM, Mag Malate in evening
  • Week #3: Add Symbioflor 1 + 2 in PM, D-Ribose with it
  • Week #4: Add Miyarisan in AM, CoQ10 in evening
  • Week #5: Stop Symbiorflor, Start L.Reuteri
  • Various gums (Mastic etc)

There is a second uBiome that also has a bifidobacteria overgrowth with no lactobacillus which I looked at in another post.

“Id love to write a a summary but It would be very short, I haven’t had any changes in symptoms except for maybe a bit of more wired-and-tired after taking symbioflor-1. ”

Basics Criteria
bifido

  • Diversity is 44%ile (I am starting to suspect that moving closer to 50%ile indicates recovery in some form)
  • No E.Coli
    • Not directly reported, but it parent is: Enterobacteriaceae  is not reported (i.e. none)
  • Akkermansia: 0 – none reported
  • ratio

It is interesting that we see a drop of diversity which may be connected to bifidobacterium being high. Bifidobacterium suppress many of the bacteria genus that are high in CFS uBiome results.

Analysis of Over Growth by Bacteria Genus

e1

  1. Turicibacter (genus) 
  2. Bifidobacterium (genus)
  3. Faecalibacterium (genus) 
  4. Blautia (genus) 
  5. Roseburia (genus) 

NUTRIENTS/ SUBSTRATES

 

INHIBITED BY

ENHANCED BY

INHIBITS

Analysis – I have marked the items only connected to Bifidobacterium in blue.

Number of Very Elusive Bacteria:

These are not overgrowth of common bacteria, but mystery bacteria who may have special traits.

elusi

Bottom Line

Melatonin Candidate

mela

This person is high in all of the genus that melatonin may reduce (see this post).  These are the triplet of genus associated with  Partial Sleep Deprivation on DataPunk.Net.

General Suggestions

Suggestions are similar to other recent analysis:

A question that I have is what the strains and species of bifidobacteria are for this patient and the earlier post of a ubiome that was also high in bifidobacteria and zero lactobacillus. This earlier post ubiome did not have any Coriobacteriacease and low Erysipelotrichaceae with the Firmicutes-to-Bacteroidetes ratio in the opposite direction (so NOT a melatonin candidate).

Given both the drop in diversity towubiomeards typical and high bifidobacteria (positive signs), I would suggest adding in some human-source lactobacillus probiotics – for example:

  • L. Reuteri –> BioGaia and Cardioviva
  • L. Fermentum ME-3
  • Shown to persist (see this post)
    • L. rhamnosus GG (Culturelle)
    • L. rhamnosus CNCM I-4036 (Human origin)
    • L. rhamnosus (573L/1-3)
    • L. plantarum  MF1298, DC13

As always, consult with your medical professional before starting or altering your supplements.

 

 

Dealing with neurologists …

I have had to deal with a neurologist — fortunately I walked into the appointment with a SPECT scan that a radiologist had read as early Alzheimer’s (I was having severe short term memory issues in the CFS flare when the SPECT was done). The session went well, he confirmed that the Alzheimer’s diagnosis was wrong and fortunately was familiar with CFS patients and deem it to be very real.

A reader wrote today

Hello, could you please link the research that shows which masses of the brain loose brain matter. I need to show this to my neurologist or she won’t help me get a spect done 😦 “

Pub Med Studies that should interest Neurologists

This is a technical post intended for neurologists, not brain fogged CFS patients.

central_nervous_system-smFrom Lactate in the brain by ME Reseach UK

  • “Mean lateral ventricular lactate concentrations measured by (1)H MRSI in CFS were increased by 297% compared with those in GAD (P < 0.001) and by 348% compared with those in healthy volunteers (P < 0.001), even after controlling for ventricular volume, which did not differ significantly between the groups. Regression analysis revealed that diagnosis accounted for 43% of the variance in ventricular lactate. CFS is associated with significantly raised concentrations of ventricular lactate, potentially consistent with recent evidence of decreased cortical blood flow, secondary mitochondrial dysfunction, and/or oxidative stress abnormalities in the disorder." [2009]
  • “Ventricular cerebrospinal fluid  lactate was significantly elevated in CFS compared to healthy volunteers, replicating the major result of our previous study. Ventricular lactate measures in MDD did not differ from those in either CFS or healthy volunteers. ” [2010]
  • ” We found elevated ventricular lactate and decreased GSH in patients with CFS and MDD relative to HVs. GSH did not differ significantly between the two patient groups. In addition, we found lower rCBF in the left anterior cingulate cortex and the right lingual gyrus in patients with CFS relative to HVs, but rCBF did not differ between those with CFS and MDD. We found no differences between the three groups in terms of any high-energy phosphate metabolites. In exploratory correlation analyses, we found that levels of ventricular lactate and cortical GSH were inversely correlated, and significantly associated with several key indices of physical health and disability. Collectively, the results of this third independent study support a pathophysiological model of CFS in which increased oxidative stress may play a key role in CFS etiopathophysiology.” [2012]
  • “Less efficient and costly processes of frontal cortex in childhood chronic fatigue syndrome. [2015]
    • “We conducted a study using a dual verbal task to assess allocation of attentional resources to two simultaneous activities (picking out vowels and reading for story comprehension) and functional magnetic resonance imaging. Patients exhibited a much larger area of activation, recruiting additional frontal areas. The right middle frontal gyrus (MFG), which is included in the dorsolateral prefrontal cortex, of CCFS patients was specifically activated in both the single and dual tasks; this activation level was positively correlated with motivation scores for the tasks and accuracy of story comprehension. In addition, in patients, the dorsal anterior cingulate gyrus (dACC) and left MFG were activated only in the dual task, and activation levels of the dACC and left MFG were positively associated with the motivation and fatigue scores, respectively. Patients with CCFS exhibited a wider area of activated frontal regions related to attentional resources in order to increase their poorer task performance with massive mental effort.”
    • scan

MRI:

    • “This study investigated responses to acute tryptophan feeding (after administration of 30 mg/kg body mass) using functional magnetic resonance imaging to investigate neural correlates of central fatigue during a cognitively demanding exercise, the counting Stroop task. Thus, tryptophan administration before the Stroop task caused distributed functional changes in primary sensory and in multimodal neocortex, including changes in a brain region, the activity of which has been shown previously to vary with conscious awareness (precuneus). Previous reports suggest that primary mechanisms of central fatigue may be predominantly subcortical. The present results demonstrate that neocortical activity changes are also found” [2007]
    • “The primary purpose of the study was to use functional magnetic resonance imaging (fMRI) to determine Results showed that mental fatigue was significantly related to brain activity during the fatiguing cognitive task but not the finger tapping or simple auditory monitoring tasks. Significant (p< or =0.005) positive relationships were found for cerebellar, temporal, cingulate and frontal regions. A significant (p=0.001) negative relationship was found for the left posterior parietal cortex. CFS participants did not differ from controls for either finger tapping or auditory monitoring tasks, but exhibited significantly greater activity in several cortical and subcortical regions during the fatiguing cognitive task." [2007]
    • “In a series of two Blood Oxygen Level Dependent (BOLD) functional Magnetic Resonance Imaging (fMRI) studies, … Within and between regions of interest (ROI), group analyses were performed for both studies with statistical parametric mapping (SPM99). Findings showed that individuals with CFS are able to process challenging auditory information as accurately as Controls but utilize more extensive regions of the network associated with the verbal WM system. Individuals with CFS appear to have to exert greater effort to process auditory information as effectively as demographically similar healthy adults.” [2005]
    • Right arcuate fasciculus abnormality in chronic fatigue [2015]
      • “Bilateral white matter atrophy is present in CFS. …Right hemispheric increased FA may reflect degeneration of crossing fibers or strengthening of short-range fibers. Right anterior arcuate FA may serve as a biomarker for CFS.”

       

 

SPECT:

  • “Radiological imaging studies (SPECT, Xe-CT, and MRS) revealed decreased blood flow in the frontal and thalamic areas, and accumulation of choline in the frontal lobe.” [Learning and memorization impairment in childhood chronic fatigue syndrome manifesting as school phobia in Japan. 2004]
  • ” Regional blood flow studies by single photon-emission computerized tomography (SPECT) have been more consistent. They have revealed blood flow reductions in many regions, especially in the hind brain. Similar lesions have been reported after poliomyelitis and in multiple sclerosis–in both of which conditions chronic fatigue is characteristically present. In the well-known post-polio fatigue syndrome, lesions predominate in the RAS of the brain stem. ” [Chronic fatigue syndrome–aetiological aspects. 1997]
  • ” Patients with chronic fatigue syndrome had significantly more defects throughout the cerebral cortex on SPECT scans than did normal subjects (7.31 vs 0.43 defects per subject, p < .001). SPECT abnormalities were present in 13 (81%) of 16 patients, vs three (21%) of 14 control subjects (p < .01). SPECT scans showed significantly more abnormalities than did MR scans in patients with chronic fatigue syndrome(p < .025).” [Detection of intracranial abnormalities in patients with chronic fatigue syndrome: comparison of MR imaging and SPECT. 1994]
  • “Compared with the Normal Control  group, the CFS group showed significantly lower cortical/cerebellar rCBF ratios, throughout multiple brain regions (P < 0.05). Forty-eight CFS subjects (80%) showed at least one or more rCBF ratios significantly less than normal values. The major cerebral regions involved were frontal (38 cases, 63%), temporal (21 cases, 35%), parietal (32 cases, 53%) and occipital lobes (23 cases, 38%). The rCBF ratios of basal ganglia (24 cases, 40%) were also reduced.” [Assessment of regional cerebral perfusion by 99Tcm-HMPAO SPECT in chronic fatigue syndrome. 1992]

Brain Matter Volume

These was the requested studies asked for by the reader. I cite the 2015 studies that links to six earlier studies.

  • Gray matter volumes in patients with chronic fatigue syndrome [2015].
    • “Although most studies found Gray Matter volumes reduced in some brain regions in CFS, as we discussed above, there are so many factors that could affect brain structure should have been considered. So far, no study has controlled all these factors.”
    • We found 6 studies focusing on the change of GM volumes. Okada et al. [34] found in a voxel-based morphometric study of CFS that GM volumes reduced in bilateral prefrontal and that the affected areas extended from Brodmann area (BA) 8 to 9 in right cerebral hemisphere and from BA 9 to 11 in left. Puri et al. [35] also found that GM declined in occipital lobe, right angular gyrus, and posterior division of the left parahippocampal gyrus in a voxel-based morphometric 3-T MRI study. de Lange et al. [36] found that global GM volumes reduced by 8% compared to healthy controls and the rate of decline is 2.2 mL/year in a cohort study; moreover, the GM volumes could increase after cognitive behavioral therapy [37].

Bottom Line

CFS/ME alters the brain in many ways. Many of the alterations correspond to symptoms.