Series on Ian Lipkin Research Results

I am starting a series, similar to the last two posts, looking at the highs and lows bacteria reported by Ian Lipkin — and what can be done to correct them. As always, I will be using publications on PubMed to list the research followed by my Bottom Line summary for the brain fogged. I will be looking at supplements, probiotics and food only — antibiotics are likely to be more harmful then helpful when we are dealing with this type of fine re-adjustment of the microbiome.

I will do one bacteria at a time. It is important to note that his results were based on the average. In reality, individuals may be all over the place. Once CFS person may be normal for one family and the next one very abnormal. The model is that of a shift of the microbiome. The shifts will not be identical in everyone because every one’s microbiome is unique when healthy (more distinct than a fingerprint!).

His 2017 paper is available here. This chart from the paper show some controls and some cfs with the almost the same values, and some with a major shift.

You cannot apply one size fit all treatment (for example the high Blautia issue in my last post impacted just 3 of 20 CFS uBiome results that I have looked at, 15%). Getting uBiome results (or equivalent) is likely helpful — whatever test you use, should measure hundreds of families.

The Bacteria to be examined

(links to the posts will be added as they are done)

  • Low
    • Pasteurellales [Order]
      • Lachnospiraceae [Family],
      • unclassified Bacillales[Family] and
      • Pasteurellaceae[Family]
    • Faecalibacterium [Genus],
    • Roseburia[Genus],
    • Coprococcus[Genus],
    • Gemella [Genus],
    • Dorea [Genus], and
    • Haemophilus [Genus]
  • High
    • Clostridiaceae [Family]
    • Clostridium [Genus],
    • Pseudoflavonifractor [Genus],
    • Anaerostipes [Genus]
    • Coprobacillus [Genus]

I have taken the liberty of copying the table from the article below (so I may link from their findings over the next month).

Diagnostic groups

Selected bacterial species





ER (%)

FP (%)

FN (%)

ME/CFS (50) vs. control (50)

[Firmicutes] Coprococcus catus






[Firmicutes] Pseudoflavonifractor capillosus

[Firmicutes] Dorea formicigenerans

[Firmicutes] Faecalibacterium prausnitzii

[Firmicutes] Coprococcus catus






[Firmicutes] Pseudoflavonifractor capillosus

[Firmicutes] Dorea formicigenerans

[Firmicutes] Faecalibacterium prausnitzii

[Firmicutes] Clostridium asparagiforme

[Proteobacteria] Sutterella wadsworthensis

[Bacteroidetes] Alistipes putredinis

[Firmicutes] Anaerotruncus colihominis

ME/CFS + IBS (21) vs. control (50)

[Firmicutes] Faecalibacterium cf






[Bacteroidetes] Bacteroides vulgatus

[Firmicutes] Faecalibacterium cf






[Bacteroidetes] Bacteroides vulgatus

[Firmicutes] Faecalibacterium prausnitzii

[Bacteroidetes] Alistipes putredinis

[Firmicutes] Coprococcus catus

[Firmicutes] Faecalibacterium cf






[Bacteroidetes] Bacteroides vulgatus

[Firmicutes] Faecalibacterium prausnitzii

[Bacteroidetes] Alistipes putredinis

[Firmicutes] Coprococcus catus

[Firmicutes] Anaerostipes caccae

[Firmicutes] Dorea formicigenerans

[Firmicutes] Anaerotruncus colihominis

[Firmicutes] Clostridium asparagiforme

ME/CFS w/o IBS (29) vs. control (50)

[Bacteroidetes] Bacteroides caccae






[Firmicutes] Pseudoflavonifractor capillosus

[Bacteroidetes] Bacteroides caccae






[Firmicutes] Pseudoflavonifractor capillosus

[Bacteroidetes] Parabacteroides distasonis

[Bacteroidetes] Bacteroides fragilis

[Bacteroidetes] Prevotella buccalis

[Bacteroidetes] Bacteroides xylanisolvens

[Firmicutes] Dorea formicigenerans

ME/CFS w/o IBS (29) vs. ME/CFS + IBS (21)

[Bacteroidetes] Bacteroides vulgatus






[Bacteroidetes] Prevotella buccalis

[Firmicutes] Ruminococcus lactaris

[Firmicutes] Eubacterium hallii

[Firmicutes] Anaerotruncus colihominis

[Firmicutes] Faecalibacterium cf

[Firmicutes] Clostridium methylpentosum

[Bacteroidetes] Bacteroides vulgatus






Bottom Line

This is a major research project. I hope by consolidating the PubMed citations that:

  • patients and their care givers can be empowered to “self-service”
  • front line MDs have a reference that they can use with detail microbiome results from uBiome and other providers
  • researchers have a sounding board for their hypothesis and proposals; ideally with trials of items suggested and seeing what the shift in the microbiome (if any) that results.

Special thanks to L.L.Ingram for encouraging me to undertake this epic project.

High Blautia — seen in some CFS Microbiomes

A long time (almost 2 decades) CFS friend got his microbiome done by I will be writing some more posts on his ubiome and history, but to get things started I want to look at the subset that have high Blautia.

As with most CFS patients, there is a relative lower level of Firmicutes — here it is under 62% are Firmicutes (ME/CFS averaged 58%, healthy controls 65% — see this post). “We observed that bacterial diversity was decreased in the ME/CFS specimens compared to controls, in particular, a reduction in the relative abundance and diversity of members belonging to the Firmicutes phylum.” [2016]

  • “Within the Firmicutes, at the family level, Ruminococcaceae were lower in the ME/CFS samples (16 vs. 11 % in ME/CFS and healthy individuals respectively)”[2016] — Ruminococcaceae are part of  Clostridium XIVa which was covered in this post.


Moving down to the Genus level we see similar to some other patients (see this post), especially the high Blautia — also seen with Patients “R” and “Q” See below. Other CFS patients had just 2-5%.


A second one done a few weeks apart, show similar results


Patient Q


Patient R


Reducing Blautia

Blautia genus (under Bacteria; Firmicutes; Clostridia; Clostridiales; Lachnospiraceae) has become a dominant Genus and consist of dozens of species. Note that it was classified under “ruminococcus”(by appearance) until RNA studies found that while it looks alike but was different. In italic and red are items to avoid, bold are items to take.

  • “some bile acids have been shown to exhibit antimicrobial activity….bactericidal activities to Blautia coccoides” [2017]
  • sodium butyrate …. elevated the abundances of the beneficial bacteria Christensenellaceae, Blautia and Lactobacillus.”[2017]
  • safflower oilincreased abundance of Blautia,[2016]
  • Japanese traditional dietary fungus koji Aspergillus oryzae functions as a prebiotic for Blautia coccoides through glycosylceramide: Japanese dietary fungus koji is a new prebiotic [2016].
  • “Bacillus subtilis…the relative abundance of Alistipes, Odoribacter, Ruminococcus, Blautia and Desulfovibrio were higher” [2016]
  • Metformin and berberine.…were markedly increased” [2015] [2016]
  • Resistant starch (RS) …  Roseburia, Blautia, and Lachnospiracea incertae sedis were decreased.” [2015] [2016][2014]
  • Blautia, Roseburia and Coprococcus were significantly enriched following treatment with hydrolyzed casein formula supplemented with Lactobacillus rhamnosus GG” [2016]
  • Blautia and Staphylococcus) significantly increased after Lactobacillus plantarum P-8 consumption,” [2015]
  • Lactobacillus salivarius Ls-33…Blautia coccoides_Eubacteria rectale group and Roseburia intestinalis, were significantly increased” [2013]
  • ” least 24 billion viable Lactobacillus paracasei DG …the Clostridiales genus Blautia (P = 0.036) was decreased;”
  • High grain diet …altered the colonic mucosal bacterial communities, with an increase in the abundance of genus Blautia and a decrease in the abundance of genera Bacillus, Enterococcus, and Lactococcus.”
  • “antimicrobial effect observed for the grape seed polyphenols, particularly against Bacteroides, Prevotella and Blautia coccoides-Eubacterium rectale.” [2015]
    • “Subjects with regular consumption of red wine (mean = 100 ml/day) had lower serum concentrations of MDA and lower fecal levels of… blautia”[2015]
  • positive associations between flavone intake and Blautia,” [2015]
  • “A negative association was found between the intake of pectins and flavanones from oranges and the levels of Blautia coccoides” [2014]
  • Rosemary Extractincreased the Blautia coccoides and Bacteroides/Prevotella groups and reduced the Lactobacillus/Leuconostoc/Pediococccus group in both types of animals.” [2014]
  • ” All treatments [a daily dose of 60 g of whole-grain barley (WGB), brown rice (BR), or an equal mixture of the two (BR+WGB)] increased microbial diversity, the Firmicutes/Bacteroidetes ratio, and the abundance of the genus Blautia in fecal samples.”

Bottom Line

There was a number of common things between this post decreasing Blautia and the last post increasing Clostridium XIVa.

  • Grapes and/or Grape seed
  • Bile Acid supplementation
  • Apple Pectin and Oranges (for it’s specific flavanones)

On the other side, we saw study after study that lactobacillus probiotics increases blautia.

  • No Bacillus subtilis probiotics (likely no bacillus of any species)
  • No sodium butyrate
  • No safflower oil.(Change to Grape Seed oil for cooking?)
  • Reduce grain intact

Increasing Clostridium XIVa

A reader wrote “it seems to me that Clostridium XIVa is a very crucial bacterial group for improving health. Can you do a blog post on how to increase these bacteria? Thank you.”

For ulcerative colitis (UC), it appears to have benefit

Scanning pubmed articles for what is known… often what we know comes from animal studies — which may or may not apply to humans.

  • ” the addition of isoflavones, with enrichment of some bacterial gut members associated with the metabolism of phenolics and/or equol production, such as Collinsella, Faecalibacterium and members of the Clostridium clusters IV and XIVa.” [2017]
  • Long-term calorie restriction induced significant shifts..enhancing the growth of beneficial microorganisms such as Bacteroides, Roseburia, Faecalibacterium and Clostridium XIVa. [2017]
    • Vegetarian and fibre-rich diets have been shown to induce beneficial changes on gut microbiota in healthy people, with reduction of Bacteroides spp., Enterobacteriaceae, and Clostridium cluster XIVa bacteria.” [2016]
    • Vegetarian diet…with lower ratio (%) of Clostridium cluster XIVa.” [2014]
    • a strict vegetarian diet (SVD) for 1 month... an increase in commensal microbes such as Bacteroides fragilis and Clostridium species belonging to clusters XIVa and IV,” [2013]
    • “polyphenol-rich plant products… lower counts of Streptococcus spp. and Clostridium Cluster XIVa in the faecal microbiota (P < 0.05).” [2014]
    • High Amylose starchClostridium clusters IV and XIVa were decreased (P < 0.01) in pigs” [2015]
    • Fasting has no impact [2015].
    • “Of particular interest, Clostridium cluster XIVa species were significantly reduced… by high-fat sucrose diet” [2015]
  • bile acid therapy[tauroursodeoxycholic acid (TUDCA), or glycoursodeoxycholic acid (GUDCA)] normalized the colitis-associated increased ratio of Firmicutes to Bacteroidetes Interestingly, administration of bile acids prevented the loss of Clostridium cluster XIVa and increased the abundance of Akkermansia muciniphila, bacterial species known to be particularly decreased in IBD patients.” [2017]
    • “Increasing levels of the primary bile acid cholic acid (CA) causes a dramatic shift toward the Firmicutes, particularly Clostridium cluster XIVa” [2013]
  • “The alfalfa diet increased (P < 0.05) Clostridium cluster XIVa abundance,” [2017]
  • “We found that the concentration of the Clostridium coccoides group (Clostridium cluster XIVa), the Clostridium leptum subgroup (Clostridium cluster IV) and the Bacteroides fragilis group had significantly increased in partially hydrolysed guar gum-fed mice.” [2016]
  • Xylo-oligosaccharides…significantly increased numbers of lactobacilli in the colon and Clostridium cluster XIVa in the ceca.” [2015]
  • resistant starch, a fiber that was not completely fermented in the colon, whereas the other fibers induced similar responses on gene expression and microbiota. Consistent associations were revealed between fiber-induced enrichment of Clostridium cluster IV and XIVa representatives” [2015]
  • “a diet enriched in 5% acidic oligosaccharides derived from pectin (pAOS)…. stimulating the growth of species involved in immunity development, such as Bifidobacterium species, Sutturella wadsworthia, and Clostridium cluster XIVa organisms, and at the same time increased the production of butyrate and propionate.” [2015]
    • “Administration of either 0.33 or 3.3% apple pectin in the diet….became more prominent represented mainly Gram-positive anaerobic rods belonging to the phylum Firmicutes, and specific species belonging to the Clostridium Cluster XIVa.” [2010]
  • Wheat dextrin mediated a significant increase in total bacteria in vessels simulating the transverse and distal colon, and a significant increase in key butyrate-producing bacteria Clostridium cluster XIVa and Roseburia genus in all vessels of the gut model.” [2013]
  • Clostridium Cluster XIVa were higher (P < 0.001) in the casein-based diets” [2014]
  • “The faecal microbiota of the omnivorous group was enriched with Clostridium cluster XIVa bacteria, specifically Roseburia-E. rectale.” [2012]
  • “Especially the Clostridium cluster IV and subcluster XIVa were particularly increased in group B,[fed a probiotic mixture of:  Lactobacillus delbrueckii subsp. bulgaricus, Bifidobacterium bifidum, Enterococcus faecium, Candida pintolopesii and Aspergillus oryzae [2011]
  • “pro-biotic yogurt containing Bifidobacterium animalis subsp. lactis LKM512… yogurt consumption, in particular, the bacterial species and phylotypes of Bifidobacterium, Clostridium cluster IV and subcluster XIVa were increased in number.” [2007]

Bottom Line

It appears that bifidobacterium probiotics will likely increase the level. Apple pectin becoming a regular diet additive is also suggested. Increasing/supplementing bile acids also appears to be well supported. Looking at Jarrow Bile Acid Factors ($20 for a month on Amazon), we see the acids cited in the above study.


The Heart and Blood of the CFS Patient

You may have a small heart

  • “Cardiovascular symptoms are common in CFS patients. Cardiac dysfunction with low cardiac output due to small left ventricular chamber may contribute to the development of chronic fatigue as a constitutional factor in a considerable number of CFS patients.” [2009]
  • “A considerable number of CFS patients have a small heart. Small heart syndrome may contribute to the development of CFS as a constitutional factor predisposing to fatigue, and may be included in the genesis of CFS.” [2008]
  • Small heart syndrome in patients with chronic fatigue syndrome[2008]. “A considerable number of CFS patients have a small heart. Small heart syndrome may contribute to the development of CFS as a constitutional factor predisposing to fatigue, and may be included in the genesis of CFS.”
  • “A small size of LV with low cardiac output was noted in OI, and its degree was more pronounced in CFS with Orthostatic intolerance  CFSOI(+). A small heart appears to be related to the genesis of OI and CFS via both cerebral and systemic hypoperfusion. CFSOI(+) seems to constitute a well-defined and predominant subgroup of CFS.”[2011]
  • “”Small heart” on the chest X-ray photograph was prevalently noted in CFS patients. Echocardiographic examination revealed that CFS patients with “small heart” had an actually small LV chamber and poor cardiac performance.” [2009]
  • From “Small Heart as a Constitutive Factor Predisposing to Chronic Fatigue Syndrome [2012]”(Full Text)



Rapid Heart Beat (Tachycardia) and POTS

A consequence of a small heart may be a tendency to increase blood flow to the body by beating faster. The small heart may also be connected to the DNA SNPs associated with CFS.

Blood Characteristics

For a good discussion on blood differences seen in CFS, see Les Simpson article in the Journal of IiME, Vol. 2 Issue , p. 24ff.

  • “Echocardiographic measures indic ated that the severe CFS participants had 10.2% lower cardiac volume (i.e. stroke index and end-diastolic volume) and 25.1% lower contractility (velocity of circumferential shortening corrected by heart rate) than the control groups.” [2009]
  • ” In conclusion, individuals with CFS have a significantly lower peak oxygen consumption and an insignificant trend toward lower blood volume compared with controls. These variables were highly related in both subject groups, indicating that blood volume is a strong physiological correlate of peak oxygen consumption in patients with CFS.” [2002]
  • Circulating Blood Volume in Chronic Fatigue Syndrome [1998]” ” Of the 19 patients reported here, abnormalities in blood volume were very common. The most common, found in 16 of 19 patients, was a reduction in red blood cell mass. Eleven subjects had low plasma volumes, and total circulating blood volume was subnormal in 12 of 19 subjects. In some individuals this abnormality was strikingly severe… red Blood Cell mass …46% of the expected normal, and a total blood volume ..which represents 49.7% of the expected normal value”
    • Objectively measured abnormalities of blood pressure variability in CFS[2012]
    • Lower blood pressure in sleep[2011]
    • Lower blood pressure[2009]

    • Less and slower variability of blood pressure (2012) (2011)
    • Lower total blood volume(8%(2009) – 9% (2002) – 15%(2009) less), plasma volume (13% (2009)) and red blood cell volume (19%) (2009)(2000)(2007)(1998).
    • 35% lower peak oxygen consumption(2002)
    • Significant decrease in red cell distribution width (2007)
    • Higher percentages of misshaped red blood cells[13] [14] (2001) (other)
    • Impaired capillary blood flow.
    • Changed red cell shape populations
    • High values for flat blood-cells
    • Percentage of deformed cells reduced with B12 injections within 24 hrs in responders (P. 245 Englebienne, P. (2002). Chronic Fatigue Syndrome: A Biological Approach.)

And now add thick blood!

  • Chronic fatigue syndrome and/or fibromyalgia as a variation of antiphospholipid antibody syndrome: an explanatory model and approach to laboratory diagnosis [ 1999]. “CFS and/or FM patients who have a hereditary deficiency for thrombophilia or hypofibrinolysis may be unable to control thrombin generation properly. We have found that three out of four CFS and/or FM patients have a genetic deficiency (unpublished data). Certain pathogens induce the immune system generation of APL antibodie s and can be a triggering mechanism for APS. Once antibodies are formed, protective proteins are dislodged from endothelial cells, exposing PS. Coagulation proteins bind on exposed PS surfaces, generating thrombin on the EC surface. Excess thrombin converts fibrinogen to SFM, which may be deposited on the EC surface and/or circulate in the plasma. Fibrin deposition leads to decreased oxygen, nutrient and cellular passage to tissues around the microcirculation. This hypercoagulable state may cause localized pathology in many tissues, yielding the systemic compromises and symptoms characteristic of the CFS-FM complex. Since this hypercoagulable state does not necessarily result in a thrombosis, but rather in fibrin deposition, we suggest that an alternative name for this Antiphospholipid antibody process would be immune system activation of coagulation (ISAC) instead of antibody-mediated thrombosis [18]. Once this hypercoagulable state is detected, appropriate anticoagulant therapies may be given to relieve patient symptoms
  • “Most symptoms of Gulf War Illness (GWI) are similar to Chronic Fatigue Syndrome (CFS) and/or Fibromyalgia (FM). We investigated whether these symptoms are associated with an activated coagulation system as has been reported in some cases of CFS/FM. The coagulation assays include activation markers of the cascade, platelet activation and hereditary risk factors. Our findings show activation of the coagulation system in GWI. This evidence of a hypercoagulable state suggests that symptoms may be due to poor blood flow and, therefore, a basis for the potential utility of anticoagulant therapy.” [2000]

Bottom Line

Recipe for CFS: Start with a small heart, then decrease it’s efficiency by having thicker blood and less blood, add in alterations of metabolites (amino acids and other chemicals) due to microbiome shifts — adding more chaos. Filter thru your DNA Snps to produce your own special collection of symptoms!

In terms of treatment:

  • Fix metabolites
  • Reduce coagulation / thick blood

Heart Problems?








Increasing Akkermansia

A reader asked explicitly how to increase akkermansia bacteria in the body, is there a probiotic available? Low levels of akkermansia is associated with obesity.

  • Melatonin: “… melatonin supplementation reversed 14 operational taxonomic units OTUs [of 69]…in particular through its ability to decrease the Firmicutes-to-Bacteroidetes ratio and increase the abundance of mucin-degrading bacteria Akkermansia, which is associated with healthy mucosa.” [2017]
  • Capsaicin (CAP) – found in cayenne peppers! “reduces body weight…showed a higher abundance of Akkermansia muciniphila, a mucin-degrading bacterium with beneficial effects on host metabolism.” [2017]
  • Lingonberries [IKEA stocks often] “The relative abundance of Akkermansia and Faecalibacterium, genera associated with healthy gut mucosa and anti-inflammation, was found to increase in response to lingonberry intake.” [2016]
  • Increased gut microbiota diversity and abundance of Faecalibacterium prausnitzii and Akkermansia after fasting: a pilot study.“Akkermanisa and Bifidobacteria increased in abundance due to intervention. The inflammation-associated gut microbes Enterobacteria and Lactobacilli increased during the first week and then declined by the end of the intervention.” [Human study — full text]
  • Table Grapes: Table grape consumption reduces adiposity and markers of hepatic lipogenesis and alters gut microbiota in butter fat-fed mice [2016]. ” tended to increase the abundance of the beneficial bacterium Akkermansia muciniphila compared to controls”
  • “First day: breakfast: Pernegg muesli (prunes, dates, raisins, flaxseed, water); lunch: potatoes and vegetables; dinner: vegetable soup.
    Second day: breakfast: herbal tea, Glauber’s salt, lunch: fresh squeezed fruit and vegetable juice, dinner: fasting soup.
    All other fasting days: breakfast: herbal tea, lunch: fresh squeezed fruit and vegetable juice, dinner: fasting soup.”

  • A probiotic for use with lab animals is cited [2017] [2016]
  • “We observed a low abundance of the mucin-degrading bacterium Akkermansia muciniphila in the mice that were fed Enterococcus faecium  NCIMB 10415 for 8 weeks.” [2012] — So Enterococcus faecium  probiotics (like symbioflor-1) should not be taken concurrent with above approaches to increase Akkermansia. 😦
  • [in terms of infants] ” In Finland probiotics were given to mothers (n = 79) for 2 months prior to and 2 months after delivery. In Germany probiotics were started in infants (n = 81) at weaning, at the latest at 1 month of age, and continued for 4 months …n breast-fed infants a trend toward higher counts of bifidobacteria was detected in Finland (p = 0.097) as against Germany, where a more diverse microbiota was reflected in higher Akkermansia (p = 0.003),”[2012] Again, an interaction between probiotics(bifidobacteria) and Akkermansia
  • ” High Fat feeding significantly reduced (P < 0.05) 1 operational taxonomic unit (OTU) of the genus Bifidobacteria (64-fold) and 5 OTUs of the genus Akkermansia (≥16-fold).”  [2016] Reduce the amount of fat in your diet!

Bottom Line

A shift reduce fat content and increase fiber content, especially fiber from fruits which in  polyphenol, appears to be an effective pattern. Table grapes and lingonberries are known to benefit. Increased tea consumption (increased polyphenols) and trying a fasting diet or Ma-Pi 2 diet are additional approaches.

I suspect that an Akkermansia probiotic could first appear in the US — given the current push for deregulation —  as long as there are no claims of actual benefits from it on the label…


Methylation revisited

A reader asked me about my hypothesize about methylation and antibiotics. I will respond to the first item in this post. The hypothesis is that DNA impacts methylation and is thus connected to some symptoms.

I have done one post on methylation in the past, Methylation, CFS and the microbiome [2016].  Methylation was a hot research topic reaching a peak in 2015 when interest started to drop according to PubMedmeth

Irritable Bowel Syndrome


  • ” Epigenome-wide analysis of DNA methylation was conducted…three CPGs reached significant p-values in the replication sample, including malate dehydrogenase 2 (MDH2; p-value 0.017), tetranectin (CLEC3B; p-value 0.039), and heat shock protein beta-6 (HSPB6; p-value 0.016)…we found evidence for the involvement of epigenetic factors. ” [2016]
  • “The majority of differentially methylated (DM) sites (91%) were attributable to increased values in the women with FM. The DM sites included significant biological clusters involved in neuron differentiation/nervous system development, skeletal/organ system development, and chromatin compaction. Genes associated with DM sites whose function has particular relevance to FM included BDNF, NAT15, HDAC4, PRKCA, RTN1, and PRKG1.” [2013]

Chronic Fatigue Syndrome

  • Epigenetic modifications and glucocorticoid sensitivity in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) [2017].
    ” we report DNA methylation differences in PBMCs of ME/CFS patients, some of which were significantly associated with overall quality of life as well as glucocorticoid hypersensitivity in a subgroup of ME/CFS patients. … we found that genes such as GSTM1, MYO3B, GSTM5, and ATP6V0E2 showed significant epigenetic modifications in ME/CFS. “
  • Epigenome-wide DNA methylation patterns associated with fatigue in primary Sjögren’ssyndrome [2016]. “Some genes involved in regulation of the immune system and in inflammation are differently methylated in pSS patients with high vs low fatigue…. the most pronounced hypomethylation in pSS high fatigue annotated to the SBF2-antisense RNA1 gene.”
  • “Overall NR3C1-1F DNA methylation was lower in [female] patients with CFS than in controls.” [2015]
  • ” We found an increased abundance of differentially methylated genes related to the immune response, cellular metabolism, and kinase activity. Genes associated with immune cell regulation, the largest coordinated enrichment of differentially methylated pathways, showed hypomethylation within promoters and other gene regulatory elements in CFS.” [2014]


While we are dealing with DNA – the changes are epigenetic (relating to or arising from nongenetic influences on gene expression — i.e. the environment, food, stress and most important, the microbiome). This page describes it better.

In summary:

“The human microbiota and epigenetic processes have both been shown to play a crucial role in health and disease. However, there is extremely scarce information on epigenetic modulation of microbiota members except for a few pathogens. … It would thus appear likely that such mechanisms are widespread for most bacterial members of the microbiota.” [2016]

Bottom Line

Yes, methylation is a significant factor for a subset of CFS patients, likely more common among female patients than male patients.  The problem is epigentic: induced issues (environment). We know very little about what  influences these epigentic changes. We know that some amino acids have an impact.

My preferred hypothesis is that the epigenetic shift is caused by a shift of metabolites (chemicals, including amino acids) produced by the microbiome. This would explain why some people with CFS and the same genes do or do not have epigenetic changes influencing methylation. It is preferred also, because it is actionable to correct the root cause! What is the root cause — a microbiome (gut bacteria) shift.  Yes, methyl-b12 may help a subset but this is treating the end result and not the root cause.




Addressing High Streptococcus: Bioscreen Report

From a reader: “Bioscreen result. I have seen a few other CFS patients’ Bioscreen data. Almost always have high streptococcus. Also, X…(… on Phoenix Rising) in 2013 had similar scores to what I currently have, when he was ill. Trying to get in touch with X… as well. Once again, thank you Ken 🙂
I gather due to your own experience multiple times with the illness; you also are an adherant of CFS being largely caused by gut bacteria/ dysbiosis? Starting to affirm this, as this is the last area of inquiry I have taken after trying to rule out all other factors. Strep overgrowth and potential D-lactate excess, in all manner of testings I’ve undergone, has of yet been the only confirmed factor.”
I’ve cited a Bioscreen result before, see this post from 2014. That report had high Streptococcus, Aerobe, and Clostridium, with low Coliforms (which include E.Coli). The results from different labs can vary greatly on what is reported. This can almost force you to become a microbiologist to make sense of the reports.
Note on above report: Only two types of streptococcus are being measured.
In this post, I will look at what can be done to reduce streptococcus without prescription antibiotics. The list is short, so I will assume that the first goal is to kill streptococcus without consideration of side effects (a.k.a. tunnel vision).

Concerning antibiotics, there is a lot of antibiotic resistance reported.

  • “A total of 2.4% (95CI%: 0.1-4.7%) of the [Streptococcus] pneumococcal strains were highly resistant to both phenoxymethylpenicillin and macrolides, whereas the highest resistance rates were to cefaclor (53.3%), followed by tetracycline (20%) and cefuroxime (12.1%).”[2017]
    • “penicillin – 5.41%, erythromycin – 8.1%, clindamycin – 4.05%, amoxicillin-6.76%, tetracycline 28.38%.” [2017]
  • “The rates of resistance and reduced sensitivity of the isolates for penicillin and ampicillin were determined at 61.2% and 55.1%, respectively. However, all isolates were found to be susceptible to vancomycin” [2016]
  • “a substantial group of strains is resistant to macrolides and the majority of strains are resistant to tetracycline.” [2016]
  • Note: Wikipedia states differently (likely old studies) “Most Streptococcus milleri strains are resistant to bacitracin and nitrofurazone, and sulfonamides are totally ineffective.[8] However, most strains studied have been shown to be susceptible to penicillin, ampicillin, erythromycin, and tetracycline.[9]

Bottom Line

Discuss with your medical professional, starting with licorice (especially Spezzata), then I would suggest Triphala because its long history of treating digestive disorders. Magnolia Bark and Olive leaf would be the next wave of supplements to try (remember to rotate!).

Because you are high in E.Coli (atypical for CFS), then Lactobacillus acidophilus LA-5 would likely do double duty. Lactobacillus acidophilus inhibits most E.Coli.

D-Lactate Excess

Concerning D-lactate excess see these two post:

Last but not least… Vitamin D3

This has slow impact. You want to move yourself into the top 10% of the “normal range”. This often means 10,000 IU/day of Vitamin D3 for a younger person. More for an older person. Amount depends on degree of malabsorption.