Celiac Disease, Microbiome – a different path?

Once a microbiome dysfunction happens, it can evolved into more symptoms as the bacteria shifts more. Some of these evolutions may put someone out of the CFS diagnosis into a different medical diagnosis.  Some of these diagnosis can be worst than CFS, i.e. Crohn’s disease.

A reader in Europe indicated several CFS/Celaic people in their group, so I will look at Celiac disease in this post.

Celiac Disease

“Celiac disease (CD) is a frequent chronic inflammatory enteropathy caused by gluten in genetically predisposed individuals that carry disease susceptibility genes (HLA-DQ2/8).” [2015]

At first browsing of PubMed, we see close associations just like “depression and CFS” has.

  • The Overlap between Irritable Bowel Syndrome and Non-Celiac Gluten Sensitivity: A Clinical Dilemma.[2015] ” Some patients with celiac disease may remain asymptomatic or have only mild gastrointestinal symptoms and thus may qualify for the diagnosis of IBS in the general clinical practice… While the treatment of NCGS is exclusion of gluten from the diet, some, but not all, of the patients with IBS also improve on a gluten-free diet. “
  • Chronic fatigue syndrome and non-celiac gluten sensitivity. Association or cause? [2015]  “From my point of view fibromyalgia and chronic fatigue (FM/CFS) are not defined diseases but just syndromic terms that reflect reality… The following case, treated during the preparation of this manuscript, illustrates this relationship: a 23 year old woman with 3 years since the onset of FM/CFS with severe fatigue … After one year of follow-up, after starting diet without gluten or dairy, she presented complete remission of all her symptoms, with a normal life, practicing sports and without medication. She chose not to eat triggering foodstuffs.”
  • Celiac symptoms in patients with fibromyalgia: a cross-sectional study[2015].  A list of typical celiac-type symptoms was developed, comparing the frequency of presentation of these symptoms between patients with fibromyalgia (N = 178) and healthy subjects (N = 131), in addition to those of celiac patients and gluten-sensitive patients reported in the literature. The frequency of presentation of every celiac-type symptom, excepting anemia, was significantly higher among patients with fibromyalgia compared to controls (p < 0.0001).”
  • Fibromyalgia and chronic fatigue syndrome caused by non-celiac gluten sensitivity. [2015] “The symptomatological similarity of both pathologies, especially gastrointestinal symptoms, suggests that at least a subgroup of patients with fibromyalgia could experience subclinical celiacdisease or nonceliac gluten intolerance.”
  • Fatigue in adult coeliac disease. [2005] “In coeliacs, fatigue is a common finding, which ameliorates with the gluten-free diet and is strictly correlated to depression although coeliacs on a gluten-free diet showed more frequent and more severe depression symptoms than coeliacs on a normal diet.”

 Microbiome Dimension

What do we know about changes in the microbiome? We have a lot detail than with IBS..

  • ” In fact, patients with celiac disease have a reduction in beneficial species and an increase in those potentially pathogenic as compared to healthy subjects. This dysbiosis is reduced, but might still remain, after a gluten-free diet. Thus, gut microbiota could play a significant role in the pathogenesis of celiac disease, as described by studies which link dysbiosis with the inflammatory milieu in celiac patients.” [2016]
  • “children following an African-style gluten-free diet for at least two years were subjected to a change of diet to an Italian-style gluten-free diet for 60 days. Significant differences were identified in the salivary microbiota and metabolome when Saharawi celiac children switched from African- to Italian-style dietary habits. An Italian-style gluten-free diet caused increases in the abundance of Granulicatella, Porphyromonas and Neisseria and decreases in Clostridium, Prevotella and Veillonella, …High concentrations of acetone and 2-butanone during treatment with the Italian-style gluten-free diet suggested metabolic dysfunction in the Saharawi celiac children.” [2015]
  • “The main differences were obtained in ecological indexes belonging to the genus Lactobacillus, with significant richness, diversity and habitability reduction in CD patients. In CD bands were categorized primarily with Streptococcus, Bacteroides and E.coli species. In HC the predominant bands were Bifidobacterium, Lactobacillus and Acinetobacter, though the Streptococcus and Bacteroides were lower.” [2015] so CD has:
    • Less Lactobacillus – ditto CFS
    • Less Bifidobacterium — ditto CFS
    • Less Acinetobacter — ditto IBS [2015]
    • More Streptococcus — ditto CFS
    • More Bacteroides — ditto IBS [2015]
    • enterobacteria tended to increase in celiac children.[2015]

Jumping to Conclusions

CD has a specific DNA SNP associated with it, FM has a series of DNA SNP associated with it. What if all of these were the same condition (a bacteria shift) — with DNA determining the symptoms/presentations?  Where as the conventional 2015 literature cites “The underlying mechanism of the disease is completely unknown and beside of gluten other wheat proteins as well as amylase-trypsin-inhibitor or short chain sugars are discussed as triggers.” [2015]

If this is true, than the IBS probiotics would also apply to CFS and CD. Similarly, other aspects of treatment for the dysfunction described on this site would also apply to CD.

What about wheat free? dairy free? — as stated in the articles, it helps some — why? because it will likely starve some of the bacteria involved (remember there are MANY MANY, see this post on IBS)

Probiotics?

Far less studies, with Bifidobacterium having positive results — just like IBS.

 

 

IBS Probiotics

The following are a list of probiotics effective (i.e. improve, not necessarily cure) Irritable Bowel Syndrome according to studies on PubMed.com. IBS is co-morbid with CFS and thus they become recommended probiotics for CFS. For this I raised the criteria to studies on humans and not on mice. In general mixtures were eliminated with the exception of “unique mixtures” – Prescript Assist and VSL#3

NOTE: Probiotics do produce natural antibiotics. It is strongly recommended that the probiotics below be rotated and not taken continuously. Two weeks on one and then move to the next. Why?  We want to minimize the risk of antiibiotic resistance to the natural antibiotics produced by the probiotics.

“Overall, more than 50% of trials presented negative outcomes. The majority of the single-strain probiotictrials employing lactobacilli or Saccharomyces were negative, whereas trials employing bifidobacteria showed positive results.” Probiotic Therapy of the Irritable Bowel Syndrome: Why Is the Evidence Still Poor and What Can Be Done About It? [2015]

“because bifidobacteria concentrations have been found to be reduced in IBS compared with healthy controls, it seems reasonable, logical and safe to use prebiotics to enhance the growth of bifidobacteria and other beneficial bacteria to improve symptoms in these patients. However, based on available evidence, general use cannot be recommended in patients with IBS [2018].

Only Positive Effects

Prescript Assist – multiple species

Symbioflor 2 – E.Coli Probiotic

Mutaflor — E.Coli Nissle 1917

Clostridium butyricum probiotics

Incidental Positive

Inconclusive or negative effects

I am tough here — if there is disagreement between studies, the probiotic is dropped into the list below. One of the main reason is that only 1 in 10(100?) negative studies get published, but every positive one gets published.

Lactobacillus Plantarum

 Yakult – Lactobacillus Shirota

VSL#3 Multiple Lactobacillus, Bifidobacterium, Streptococcus

Lactobacilus GG

May be effective for children only.

Bottom Line

Lactobaccilus probiotics all show little effect (and possibly negative effect). Prescript Assist, E.Coli Probiotics and Bifidobacterium probiotics show effects (but only one strain is well reported).

A Review of how little we know about gut bacteria

T0day I came across an article entitled: The first 1000 cultured species of the human gastrointestinal microbiota [Oxford University Press, 2014). While technical, it has lots of diagrams and picture. It really illustrate how little we know about the bacteria in out guts (and their dysfunction)

First hard fact is the last 15 years, some 30% more species have been identified and it is really taking off with improve scientific techniques.

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Many of the bacteria species actively involved with FM, CFS, IBS etc may still be awaiting discovery! Worst still, we do not know which antibiotics impact which of these 1000+ species – which makes the use of antibiotics more guessing than science.

Irritable Bowel Syndrome

I am going to extract all of the differences seen with IBS cited in this article to illustrate the many many facets of the microbiome dysfunction that exists.

“The Bifidobacterium spp. are assumed to have a beneficial effect on health (Mitsuoka, 1990) and several members of the Bifidobacterium genus are commercially applied as probiotics. The most relevant observation is that these bacteria have decreased abundance in relation to a number of diseases including vitamin K deficiency (Benno et al., 1985), atopic diseases (Kalliomakiet al., 2001), irritable bowel syndrome (Kerckhoffs et al., 2009; Rajilić-Stojanović et al., 2011), and autism (Wang et al., 2011a). Moreover, Bifidobacterium spp. represent a very stable component of the gastrointestinal microbiota of each person, the composition of which hardly changes throughout years (Rajilić-Stojanović et al., 2013b).”

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The Bifidobacterium Tree

 “Because of their broad metabolic potential, the role of the Bacteroidetes in the gastrointestinal microbiota is complex: while the reduced abundance of the Bacteroidetes in some cases is associated with obesity (Ley, 2010) and irritable bowel syndrome (Rajilić-Stojanović et al., 2011), this bacterial group appears to be enriched in patients suffering from type 1 and type 2 diabetes (Larsen et al., 2010).”
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The Bacteriodetes Tree

 

” Little is known about the function of these bacteria in the ecosystem, but it is noteworthy that two independent studies have shown that members of the Bacillales order, more specifically Aneurinibacillus spp., have an increased abundance in feces of irritable bowel syndrome patients (Krogius-Kurikka et al., 2009; Rajilić-Stojanović et al., 2011),”
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“The gastrointestinal Lachnospiraceae include Dorea spp., which are the major gas producers in the gastrointestinal tract and its end-products of glucose fermentation include both hydrogen and carbon dioxide (Taras et al., 2002). Dorea spp. were found in an increased in abundance in both pediatric and adult irritable bowel syndrome patients (Rajilić-Stojanović et al., 2011; Saulnier et al., 2011), which probably could explain the symptom of bloating, experienced by the majority of these patients.”
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“Christensenella/Catabacter group were reported to be dramatically (20-fold) depleted in fecal samples of ulcerative patients relative to controls (Rajilić-Stojanović et al., 2013a) and significantly (fivefold) depleted in fecal samples of patients with postinfectious irritable bowel syndrome (Jalanka-Tuovinen et al., 2013).”
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“Currently, there is no evidence about the role of Veillonella spp. in human health, although several studies have shown an increased abundance of Veillonella spp. in fecal samples of irritable bowel patients (Malinen et al., 2005; Tana et al., 2010; Saulnier et al., 2011), which could indicate an increased transit of the ileal microbiota to the lower part of the gastrointestinal tract.”
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“A recent study has indicated that members of the Gammaproteobacteria and in particular Haemophilus spp. are elevated in irritable bowel syndrome pediatric patients (Saulnier et al., 2011). Members of the same phylogenetic group were found to correlate with irritable bowel syndrome symptom score in an independent study (Rajilić-Stojanović et al.,2011).”
“a recent study has shown a highly significant (fourfold) reduction of methanogenic archaea in irritable bowel syndrome patients relative to controls (Rajilić-Stojanović et al., 2011).”
“, the latter research has suggested that D. fragilis might be associated with a number of diseases including diarrhea, abdominal pain, anorexia, irritable bowel syndrome or allergic colitis (reviewed in Johnson et al., 2004).”

Implications

Many of the bacteria species cited above that are low, in fact most, are not available as probiotics. The species that are high are not easy to treat with antibiotics because you do not want those antibiotics to also be effective against the low ones.

This is why I keep describing my approach as a model — it tells what needs to happen but not how to make it happen.  Clinical studies with different probiotics that were found consistently effective for IBS are a staring point — but each probiotic will likely help with just part of the process.

 

Lactobacillus Plantarum

This species originally appeared to be one of the good lactobacillus. I though after yesterday’s post, it would be good to drill down into it to be sure.  Swanson sells it as a single species probiotic.  Most of the studies are for specific strains (which are not currently on the market).

At a high level, it looks very good

” L. plantarum attracted many researchers because of its wide applications in the medical field with antioxidant, anticancer, anti-inflammatory, antiproliferative, anti-obesity and antidiabetic properties.” [2016] [Full Text]

and drilling down into some details, it continue to look good

BUT then I hit this set of studies for IBS

Bottom Line

If you have IBS, definitely avoid this one. While it has some good benefits for things like aluminum – it seems not to be a good choice for CFS/IBS. IBS studies are a good proxy for CFS (when no studies exist), and multiple studies show no effect (for the same strain that occasionally have positive effect), or negative effect.

Ken’s Rule: If a probiotic has been tested for IBS with good results (and no bad ones) then it is recommended. Good results with other digestive issues — but no IBS, also recommended. No results or negative, places it in the suspect camp.

My favorites are:

  • Prescript Assist
  • Mutaflor
  • Symbioflor-2

 

 

Aluminum, Vaccines and CFS

One of my reader is involved with a group of CFSers in Europe and one of the members got a lab report that they were very high in aluminum.  This is a testable and have been associated with a subset of CFS patients and associated with vaccines. In other words, a subset of people that are very sensitive to aluminium.

  • ” Concerns linked to the use of alum particles emerged following recognition of their causative role in the so-called macrophagic myofasciitis (MMF) lesion detected in patients with myalgic encephalomyelitis/chronic fatigue/syndrome. MMF revealed an unexpectedly long-lasting biopersistence of alum within immune cells in presumably susceptible individuals, stressing the previous fundamental misconception of its biodisposition. ” [2015]
  • “Macrophagic myofasciitis and chronic fatigue syndrome are severely disabling conditions which may be caused by adverse reactions to aluminium-containing adjuvants in vaccines. While a little is known of disease aetiology both conditions are characterised by an aberrant immune response, have a number of prominent symptoms in common and are coincident in many individuals. Herein, we have described a case of vaccine-associated chronic fatigue syndrome and macrophagic myofasciitis in an individual demonstrating aluminium overload.” A role for the body burden of aluminium in vaccine-associated macrophagic myofasciitis andchronic fatigue syndrome [2009].
  • ” The results indicate that patients had significantly increased serum aluminum and decreased iron compared to controls. ” Serum concentrations of some metals and steroids in patients with chronic fatigue syndrome with reference to neurological and cognitive abnormalities [2001].
  • ” Al deposits in the macrophages, and Al assays (in μg/g, dry weight) were 768.10±18 for the patient compared with the two control patients, 5.61±0.59 and 9.13±0.057.” [2012]

Most of this work is done in France and tend to be ignored in the US (or if raised, dismissed as quackery!).

There is a nice table of the aluminum content of foods here. ” processed foods contained more aluminium than the primary products. Consequently, food was considered to be increasingly contaminated by aluminium packaging “.

Aluminum is found in consumer products including: • antacids • astringents • buffered aspirin • food additives • antiperspirants • cosmetics  [cdc]

There have been no study that I could find comparing aluminum levels in general CFS patients against controls. We need such a study. If the level of aluminum increases with the duration of CFS, then it is likely that the CFS body is not able to remove the aluminum in food.

Jumping to Assumptions

Do not immediately blame a vaccine / aluminum for CFS — at least, not until laboratory tests confirm high level of aluminum (which could also come from food — especially rice), Another factor could be the water you drink ” This study suggests that phosphate restricts the entry of Al into the cell, while fluoride promotes it.” [1998] For more effects of aluminum see this paper.

There have been individual cases reports, 2008 Story, but with 5 vaccinations,  the immune response to the vaccines could also be the cause. We cannot be sure.

The patient above grew up next to a recycler and that was their likely source of aluminum.

Caused of OR Caused by?

The finding that some lactobacillus are involved with the removal of aluminium combined with very low lactobacillus in CFS patients opens the possibility of aluminium building because the normal bacteria that would reduce it is not there!

This could be a compounding cycle of no bacteria -> increased aluminum –> CFS-like symptoms —> aluminum reducing other bacteria families.

We do not know — but we should be open to both views…  we need appropriate studies on a large population of CFS patients to resolve this question.

Treatment?

Note we are not talking about Aluminum Toxicity, but aluminum disruption of the immune system. There is considerable evidence that it will impact certain bacteria [The bactericidal action of highly purified aluminum and certain aluminum alloys [1969]., Aluminium toxicity and binding to Escherichia coli [1991].