uBiome and recovering CFS/IBS patient

A reader that have been following the model with great improvement shared their latest uBiome results. It has some interesting data points which I wish to review.

The patient is not 100% Recovered

My working definition of recovered using uBiome is having a ratio of firmcutes to bacteroides between 2.2:1 and 1.9:1. This patient is at 1.4:1 in April 2017, in January 2017 they were at 1.1:1; they are moving in the right direction but have some distance to go still.

  • Akkermansia (usually low in CFS):   Jan – 1.42% (71%), April 5.68% (287%)

shift

Can you alter your microbiome? Looking at the Order changes shown below over 3 months, the answer is a clear yes!

Alter

Bifidobacterium and Lactobacillus at or above normal levels

levels

What is very interesting is that after January, 2017 — there was considerable (major) stress on the person in this period — this may not be the cause of the decline, but personally, I consider it a contributor. Learning to deal with stress, flight or short fight or indifference are essential skills.

Looking at the split between Bifidobacterium and Lactobacillus,

  • Bifidobacterium: 176% in January, dropping to 0% in April
  • Lactobacillus: 3% in January, dropping to 2% in April
  • Diversity dropped from 97%ile to 89%ile.

Diet specific comparisons

uBiome provides comparison with average person and heavy consumers of certain things.

choices

In corresponding with this person, they saw that they were low on the Kefir bacteria chart compared to those  who eat Kefir regularly and (thanks to residue brain fog that is progressively clearing) concluded that they need to eat more Kefir.  They were at the average level of non Kefir people. There is no need to add Kefir (or anything else) when you are at the average level for that.

A surprise on raw milk bacteria

This person does not consume raw milk, but the bacteria associated with raw milk have been increasing. This is a good thing. More diversity.

rawmilk

Interesting factoid on consuming raw honey

Some patients have reported improvement from raw honey. The uBiome cites Clostridium butyricum as being in it; this is available as a probiotic (on my recommended list) Miyarisan.  For this patient, they appear to be low… a little raw honey  or Miyarisan would be suggested.  Honey brings lactobacillus kunkeei which is not available as a probiotic.

bee

Increase of Rare Bacteria also occurred with stress

It seems that a higher number of rare bacteria is an indicator for severity of CFS. This would be expected by the model. In January (pre-stress), these bacteria were seen in 1 of 10 healthy controls. Come April, we had the rare Caldicoprobacter, Gallicola, Mobiluncus suddenly appearing, and a few more common one appearing too: Gelria, Thermoanaerobacteraceae, Atopobium. One disappeared, Acidaminococcus — this bacteria uses amino acids as an energy source and its disappearance may imply the amino acids available in the gut has shifted (either not being produced enough OR some other bacteria hogging them).

Jan 2017 April 2017
janub aprub

Bottom Line

Heading into January, this patient was shifting nicely — correcting the typical CFS shifts. While no significant supplements changed, the appearance of heavy duty stress impacted the microbiome greatly …. the major change was that of Bifidobacterium disappearing!!! A secondary impact was the appearance of several rare bacteria.

Suggestions for the patient:

  • The stress is a hiccup. It has ended and time to get back to the model with a little preparation for the next stress event.
  • Invest in stress-coping techniques — may be prayer, may be yoga, may be self-help books, may be classes.
    • Whenever stress appears — write down plans for how to deal with it
      • Fight – Mark on a calendar when the fight will stop
      • Flight – May be disassociate with people, having excuses to miss meetings, etc
      • Ignore aka let-go of the stress. resignation (What will be will be – Que Sera,Sera!)
        https://www.youtube.com/watch?v=azxoVRTwlNg
  • Resume with heavy dosages of Bifidobacterium
    • Consider adding some Lactobacillus (see this post)
    • Take Ashwagandha regularly for at least 2 months.

As a personal note — I am very aggressive in seeking a low stress workplace. If there are dysfunctional managers or co-worker, I start looking for a new job with the simple rule:

  • If I cannot get the work stress resolved in 2 months (including doing a HR request under ADA if my physician is willing to write a letter), and
  • I am offered a job at a financially tolerable salary which appears to have less stress
  • Then I will take the job and give the minimum required legal notice to my employer.

As a recovered CFS patient, you must protect your health (and uBiome results).

Whey, Colostrum and Goat Milk

Back around 1999-2002, the use of whey, colostrum and goat milk for CFS was popular. My wife was positive for EBV and after 2 months of an EBV specific colostrum, became negative. This was a pre-antibiotic treatment: You infect a pregnant cow with infection X and once the cow calved, you collect the milk which will high in antibodies programming against infection X.  This method was far more expensive than antibiotics and did not scale well…. hence it was forgotten once antibiotics came along. Unfortunately, this EBV specific form of colostrum is no longer available.

Colostrum and milk are rich in proteins and peptides which play a crucial role in innate immunity when transferred to the offspring and may accelerate maturation of the immune system in neonates.” [2005]

A reader asked about these, so a fresh look at the literature is done below.

Human versus Cow Milk

The chart below illustrate well the difference [source]. They are VERY different.

Milk

Colostrum

Colostrum (known colloquially as beestings,[1]bisnings[2] or first milk) is a form of milk produced by the mammary glands of mammals (including humans) during pregnancy. Most species will generate colostrum just prior to giving birth. Colostrum contains antibodies to protect the newborn against disease. In general, protein concentration in colostrum is substantially higher than in milk.” [Wikipedia]

It is heavily promoted in some alternative health circles [Example by a provider with citations to studies]

Whey

Whey protein is a mixture of globular proteins isolated from whey, the liquid material created as a by-product of cheese production. [Wikipedia]. As you can see from the figure above, why content varies according to source.

Back in 2000, “Non-denatured Whey” was a hot topic. “Undenatured whey protein isn’t heat-treated, so the fragile bonded cysteines that later form glutathione aren’t broken down in pasteurization.”[source] — so no pasturization (or homogenization) so the chemical structures of the whey are not damaged. At a philosophical level, this appears logical.

Other Non-Cow Milks

Looking at other milks, we find that Goat’s milk has less β-lactoglobulin (closer to human milk in a weak sense).

othermilk

“Because an increase in the plasma Trp-LNAA ratio is considered to be an indirect indication of increased brain serotonin function, the results suggest that dietary protein rich in alpha-lactalbumin improves cognitive performance in stress-vulnerable subjects via increased brain tryptophan and serotonin activities.” [2002]

” The main components of whey proteins in camel milk and colostrum were similar to that in bovine, except for the lack in β-lactoglobulin.” [2007]

Bottom Line

There are no PubMed studies on whey and CFS/FM/IBS. There was one study for FM and one for IBS, one for CFS (by a questionable author – conflict of interests)

  • “The objective of this clinical pilot study was to examine the induction of apoptosis in mononuclear cells on treatment of patients with chronic pain syndrome with oral immunoglobulin produced from bovine colostrum (BCC)….These results were accompanied by a relief of the pain symptoms [in 3 out of 4 patients]” [2009]
  • “After 4 weeks (i.e. immediately after treatment), the endotoxin levels of [IBS] patients in the colostrum group showed a decrease in 44.4% (4/9) patients, no interval change in 11.1% (1/9) patients, and an increase in 44.4% (4/9) patients.” [2014] – helps some, makes other worst!
  • Inconclusive (but positive) study for Gastrointestinal Infections[2008]

I would recommend trying them, especially the high alpha-lactalbumin whey Isolate because of it’s impact on cognitive function and also improvement of sleep.  Please be aware that results are mixed — it’s a for better or for worst supplement.

I wish the infection specific colostrum were still available, and would love to see one specific for staphylococcus aureus [post].

 

“”

 

Hyperacusis, Phonophobia and DNA SNPs

I have done summary of different DNA variations associated with CFS/IBS/FM before:

My model has DNA + microbiome shifts –> Symptoms. The DNA reduces tolerances for swings of metabolites produced the microbiome and with a dysfunctional microbiome, some people are pushed over a threshold and develop symptoms. Fixing the microbiome is possible today, fixing DNA is likely a few decades off.

I happened to stumble across some PubMed studies involving hyperacusis, phonophobia and DNA Snps. This post looks at what I found for other conditions with hyperacusis or phonophobia.

Phonophobia (light sensitivity)

  • “Dopamin Beta Hydroxylase gene +1603C>T polymorphism” [2016]

Hyperacusis (noise sensitivity)

The recognized associated conditions [2003] are

Peripheral Central
Bell’s palsy Migraine
Ramsay-Hunt syndrome Depression
Stapedectomy Post-traumatic stress disorder
Perilymph fistula Head injury
Lyme disease
Williams syndrome
  • ” The most informative marker (69%) was D7S1870, followed by Hei (55%) and ELN 17/exon 18 (44%). The microdeletion was present in 56% and absent in 22% of patients….Two of the syndrome characteristics (an overfriendly personality and hyperacusis) were more frequent in the microdeletion group and these differences were statistically significant (p = 0.006 and p = 0.02, respectively).” [2010]
  • ” OCRL gene deletion revealed involvement of several flanking repeat elements… hyperosmia and/or hyperacusis were reported recurrently.” [2015]
  • “hemizygosity for a chromosomal deletion at 7q11.23…  hyperacusis [1999]

 

 

A new uBiome Result

A reader asked me to look at the results they just got back. I was pleasantly surprise to see some significant improvements in their report

Lactobacillus and Bifidobacterium is now reported

bif

This is a classic CFS profile!

Akkermansia is cleanly reported

akk

Again, a classic CFS result. See this post on Increasing Akkermansia I did earlier.

Rare Bacteria are listed simply

rare

Checking a few other uBiome results that I could access, we did find a strong pattern for three. And an over representation (25% of the CFS samples versus 13% of general samples)

  • Thermonaerobacterales 2/8
  • Gelria:  2/8
  • Synergistaceae: 2/7
  • Low Akkermansia 6/8
  • Low Lactobacillus 8/8
  • Low Bifidobaceria 7/8

One reader was very rich in rare results:

veryRare

Bottom Line

Three groups appear to be very common as low to non-existent

  • Akkermansia  75%
  • Lactobacillus 100%
  • Bifidobaceria 87%

There is work going on in getting an Akkemansia probiotic approved for sale. Remember to avoid most lactobacillus because it will push out bifidobacteria… instead, focus on only bifidobacteria probiotics.

Metabolism Reports

Another new set of reports have been added, as shown below. This is done using data derived from the KEGG Pathway Database,

Mata

Each of these can expand, for example:

lipid

We see two items of interest, ALA (alpha-linolenic acid metabolism) is low and Arachidonic acid metabolism is high. See ALA article and Arachidonic acid metabolism: role in inflammation (1991)

  • So, taking ALA supplements would be strongly suggested

Spot checking other ubiome results, I saw one reader had

  • D-arginine and D-ornithine metabolism being a very low 0.09x
  • Flavonoid biosynthesis a low 0.27x

Again, this hits at specific supplements in lieu of gut bacteria doing their jobs.

Bottom Line 2

The ubiome results give much more friendly data and at a low cost. If you are unsure that you have CFS/IBS/FM, then comparing your results to the above may answer the question. Of greater interest is the additional tables of what part of the KEGG pathway may suggest supplementation.

 

Genetic Thick Blood Tests for CFS.

Back in 1999, Dave Berg (Hemex Labs) publised “Chronic Fatigue Syndrome (CFS) &/or Fibromyalgia (FM) as a Variation of Antiphospholipid Antibody Syndrome (APS): An Explanatory Model and Approach to Laboratory Diagnosis. and stated “We have found that 3 out of 4 CFS &/or FM patients have a genetic deficiency”. A reader wrote yesterday:

  • “I have APS.  Positive on Lupus Anticoagulant. …and now some clogged veins (ischemia disease) and perivascular tunnels. Having POTS also doesn’t help…Latest to tack on is Sojogrins to all the others… Dad had three strokes”

Hemex has been sold, Berg has retired, and their specialize suite of coagulation for CFS is no longer available 😦 . The reader asked for what tests to get to detect these defects. I had testing from Hemex, and had a known defect — fortunately one that was easy to compensate for with Piracetam and Tumeric(with pepper). In fact, 4 out of 4 that went for testing were positive, with some 5 different defects (one had three of them!).

These are the tests that should be done for hypocoagulation (thick blood) and how often they are found in the general population.

Bottom Line

There have been no followup study done on CFS/FM patients to see how their incidence of the above conditions compare to the general population. In theory, the incidence would be much higher with likely 80% having at least one of the above.

There is usually difficulty getting testing for the above until after a blood clot happens. A CFS/FM patient with apparent blood circulation issues (i.e. face and skin being ‘grey’, brain fog) would likely benefit from such testing.


 

Inherited dimensions for CFS/FM/IBS

A reader forward me a link to “Find the cause of fibromyalgia” article (Spanish) which states:

  • “Thanks to a study carried out with 3,000 people – of which two thirds of them were affected by fibromyalgia and chronic fatigue – it has been possible to determine that there are 90 polymorphisms in the DNA of the patients that affect the nervous and nervous system.” I have a few of them listed in this 2016 post.

The problem with DNA causing FM/IBS/FM etc, it the tendency towards resignation (“It’s in my DNA — how can we fix it!!!”).  This is very wrong, a very important concept to remember is epigenetics – “In simplified terms, epigenetics is the study of biological mechanisms that will switch genes on and off.”[A Super Brief and Basic Explanation of Epigenetics for Total Beginners]. The key factors of turning genes on and off are items like stress and diet (including availability of minerals, amino acid etc – often a by product of the microbiome).

Microbiome is also inherited in two ways

“microbes (and their genetic material, collectively known as the microbiome) within the body can influence all kinds of traits as disparate as digestion and behavior, and can be passed down to offspring, he says. Just like a person’s own DNA.” [Newsweek]

“A genome-wide association analysis of over 1,000 twins in the UK supports that some parts of our microbiomes are inherited and shaped–not through a spread of microbes from parent to child, but through our genes. The results, revealing new examples of heritable bacterial species–including those related to diet preference, metabolism, and immune defense — appear May 11 in Cell Host & Microbe‘s special issue on the “Genetics and Epigenetics of Host-Microbe Interactions….The investigators used the genome-wide association approach to look for connections between genetic variations between twin pairs and certain bacterial types that were present and stable in the study subjects.” [Science Daily]  So DNA impacts the microbiome … but the microbiome is much more changeable than DNA!

Model

  • “Events” trigger DNA to turn some FM/IBS/CFS genes ON (epigenetics)
    • Same event to someone else with different DNA has no problems.
  • The change of genes may also result in alteration of the microbiome

Model prediction

  • Create an epigenetic event by altering microbiome, supplements.
  • Epigenetic events shuts down the genes.
    • Remission (NOT cure).

Bottom Line

There is no defined universal protocol possible for CFS/FM etc. We have at least 80 SNPs for FM, likely a similar number for IBS, CFS etc. Each person has some combination (not all of them), which supported the epigenetic change/microbiome change. The microbiome changes are likely even more complex.

There are commonality that most patients have in common. You may be high in one bacterial genus and the CFS person next to you may be low in the same genus.  What is common are low lactobacillus, low bifidobacterium, low in typical E.Coli (possibly high in atypical E.Coli), low in typical Enterococcus (possibly high in atypical Enterococcus).

With this complex situation, we have very little research, extremely few tools,  and the tools tend to be crude. In one way we have a big box of nuts and bolts in front of us and a bunch of metal connectors with different size holes in them. Some nuts and bolts are metric and some are SAE. This does not mean we are helpless — it means we need to be patient to find the right nut to match with the right bolt and then find the right metal connector where it is a tight fit. There is no handy IKEA assembly manual with all of the parts nicely bagged.

The stuff goes together if we approach it in an organized manner. Take one nut at a time, try different bolts until you have some possible matches. If frustrated, go on to the next nut (or bolt).

What are these nuts, bolts and connectors — herbs, spices, supplements, probiotics and antibiotics. Not all will be needed by everyone. Trying too hard to fit a nut to a bolt may end up jamming it.

Vitamin D and the Microbiome

In my last post we found that magnesium enhanced the growth of bifidobacteria and lactobacillus — two groups of bacteria that CFS patients are low in. The majority of PubMed studies found that it also improve symptoms. Yet magnesium levels were found to be normal in blood cells — which raise the issue of “selective rationing of minerals and vitamins to the most critical components”. The blood is far more critical to maintain magnesium levels than incidental bacteria in the gut. Often testing assumes that the body is naive and does not do selective rationing.

In this next re-examination of supplements shown to help CFS/FM/IBS, I will look at Vitamin D. I have written often about the need to take sufficients (Mythology of Vitamin D toxicity,  changes from increasing Vitamin D, Vitamin 25D and 1,25D). A few citations:

  • “This study demonstrates for the first time a direct antiviral effect of vitamin D in an in vitro infectious virus production system.”[2011]
  • “vitamin D is the environmental factor that most strongly influences autoimmune disease development.”[2015]
  • “A significant negative correlation between vitamin D level and widespread pain index was found.”[2012] i.e. FM
  • Serum 25-Hydroxyvitamin D3 and BAFF Levels Are Associated with Disease Activity in Primary Sjogren’s Syndrome [2017].  “Female SS patients had significantly lower vit D levels  than controls” [2015]
  • “Our findings showed that the high-dose supplementation of vitamin D[9 of 50000 IU cholecalciferol capsules for 3 months taken at weekly intervals] affects measures of systemic inflammation: reductions in High-Sensitivity C-Reactive Protein level and Neutrophil-to-lymphocyte ratio (NLR) distribution.” [2017]
    • “The results of the meta-analysis of 10 trials involving a total of 924 participants showed that vitamin D supplementation significantly decreased the circulating hs-CRP level by 1.08 mg/L” [2014]

A longer quote from this year is beneficial

“Vitamin D was first discovered as the curative agent for nutritional c, and its classical actions are associated with calcium absorption and bone health. However, vitamin D exhibits a number of extra-skeletal effects, particularly in innate immunity. Notably, it stimulates production of pattern recognition receptors, anti-microbial peptides, and cytokines, which are at the forefront of innate immune responses. They play a role in sensing the microbiota, in preventing excessive bacterial overgrowth, and complement the actions of vitamin D signaling in enhancing intestinal barrier function. Vitamin D also favours tolerogenic rather than inflammogenic T cell differentiation and function. Compromised innate immune function and overactive adaptive immunity, as well as defective intestinal barrier function, have been associated with IBD. Importantly, observational and intervention studies support a beneficial role of vitamin D supplementation in patients with Crohn’s disease, a form of IBD. This review summarizes the effects of vitamin D signaling on barrier integrity and innate and adaptive immunity in the gut, as well as on microbial load and composition. Collectively, studies to date reveal that vitamin D signaling has widespread effects on gut homeostasis, and provide a mechanistic basis for potential therapeutic benefit of vitamin D supplementation in IBD.” [2017]

Now for some interesting links:

Bottom Line

The understanding of what Vitamin D does have changed over the last decades. Originally, it was know to cure rickets (and the recommended dosage became some 50 Iu/day), then it impacted bone loss and the dosage increased.  Today, we find that it is implicated in many areas, impacting the distribution of bacteria in the microbiome, and needed for a healthy gut microbiota.

The biggest problem is that MDs are often behind the times and do not work from the latest literature.  For example a single dosage of 600,000 IU of vitamin D is deemed safe on medscape, or 10,000 IU/day for months [source]. One of the studies above cited an average of 60,000 IU/day for 3 months!  [2017]