LOW Akkermansia is associated with a variety of conditions according to the Smart Gut test, including Crohn’s Disease and Obesity.

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.”

  • The modulatory effect of infusions of green tea, oolong tea, and black tea on gut microbiota in high-fat-induced obese mice[2016]. “Tea consumption has been identified to have an anti-obesity effect…it was revealed that tea infusion consumption substantially increased diversity and altered the structure of gut microbiota.”
  • ” the fibre-rich macrobiotic Ma-Pi 2 diet… resulting in an increase of the ecosystem diversity and supporting the recovery of a balanced community of health-promoting SCFA producers, such as Faecalibacterium, Roseburia, Lachnospira, Bacteroides and Akkermansia.”[2016] [British Medical Journal description of this diet is here: bmjdrc-2014-000079supp]
• A probiotic for use with lab animals is cited [2017] [2016]
  • Akkermansia muciniphila: a novel functional microbe with probiotic properties[2016]. “Moreover, products containing A. muciniphila are not on the market and are thus controlled by the Novel Foods Regulation, which requires extensive safety assessment.”
• “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!
• “pH 5.5–8.0, with optimum growth at 37 C and pH 6.5″ [2004] – thus an alkaline environment would inhibit it some what.

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…

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 PubMed

Irritable Bowel Syndrome

• Genome-wide DNA methylation profiling of peripheral blood mononuclear cells in irritable bowel syndrome[2016].
  • “Genome-wide DNA methylation profiling of IBS patients compared with HCs identified 133 differentially methylated positions (DMPs) (mean difference ≥10%; p < 0.05).”
  • Epigenetic changes in differential methylation of subcommissural organ (SCO)-Spondin (SSPO) gene were positively correlated with hospital anxiety and depression scores in IBS patients (r > 0.4 and false discovery rate <0.05).
• Peptide Therapeutics and the Pharmaceutical Industry: Barriers Encountered Translating from the Laboratory to Patients [2016]. Severe difficulties in using simple solutions — they don’t work!

Fibromyalgia

• ” 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]

Bacteria

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.

• The Helicobacter pylori Methylome: Roles in Gene Regulation and Virulence[2017].
• “High-fat diets (HFD)  has been reported to induce DNA methylation changes in white adipose tissue” [2017]
  • Mechanisms for the induction of gastric cancer by Helicobacter pylori infection: aberrant DNA methylation pathway [2017].
• Identification of a Pseudomonas aeruginosa PAO1 DNA Methyltransferase, Its Targets, and Physiological Roles [2017]. A bacteria which can undergo methylization changes (which impacts what gets delivers to the body)
• Pathogenic mechanisms of intracellular bacteria[2017]. “Epigenetic regulators produced by intracellular bacteria alter the epigenotype and gene expression pattern of host cells and play an important role in pathogenesis.”
  • Changes in methylation of genomic DNA from chicken immune organs in response to H5N1 influenza virus infection[2016].
• Wilson Disease: Epigenetic effects of choline supplementation on phenotype and clinical course in a mouse model [2016]. The impact on increase in one amino acid changed the epigenetic state.

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  (1000 mcg/ 1 mg seems to be the effective ongoing dosage, see this post) may help a subset but this is treating the end result and not the root cause.

“Hi Ken,

• Reg’Activ Detox & Liver Health, 60 Capsules – 6 billion CFU

• Reg’Activ Immune & Vitality Capsules, 60 Count – 4 billion CFU

The answer is simple, start with the lower dosage one.  Some readers have reported major herx from this probiotic. If you have capsule making equipment, consider splitting the capsules into smaller dosages.

Back to the above issue. The herx/histamine causing bacteria consisted of:

First, remember that doing single species probiotics is the safest path when practical (ideally with the strain named — above lack any strain information 😦 )

Second, search pubmed, it is not hard, just enter the words!

https://www.ncbi.nlm.nih.gov/pubmed/?term=bifidobacterium+lactis+histamine

• “Human peripheral-blood-derived mast cells were stimulated with Lactobacillus rhamnosus (L. rhamnosus) GG (LGG(®)), L. rhamnosus Lc705 (Lc705), Propionibacterium freudenreichii ssp. shermanii JS (PJS) and Bifidobacterium animalis ssp. lactis Bb12 (Bb12)” [2011] mast cell stimulation releases histamine.
• “Bifidobacterium bifidum G9-1… whereas those in mast cell mediators, histamine and cysteinyl leukotrienes were not [suppressed].” [2015]
• “Bifidobacterium infantis and Bifidobacterium longum… Prolonged treatment …significantly suppressed both the allergy-like behaviors and all of the above mentioned factors involved in histamine signaling.” [2008]

In other related articles, bifidobacterium reduced allergies over 2-4 months.  It appears that this may be due to this bacteria displacing higher histamine producing  bacteria over time. It does not mean that these probiotics do not produce histamine.

Bottom Line

Go slow and gentle with probiotics.  Antibiotics, herbs and spices flow thru the body with a drop of 50% (half-life) in a few hours usually.  Probiotics are living creatures that may not drop, but increase!! When you have too severe a probiotic herx, it can become a challenge to moderate it. A high dosage of probiotics that you do well with, may help — you are trying to displace the herxing probiotics.

In some cases, there are other probiotics known to be hostile. For example, lactobacillus and Clostridium butyricum (Miyarisan) will moderate E.Coli probiotics.

Start with low dosages and slowly work up — if you slip into a herx, it may last a much longer time than expected.

A reader commented that she, like a friend, evolved into atypical Crohn’s Disease from CFS. On the surface, it means something that looks like Crohn’s Disease but does not behaves typically or appears typically how Crohn’s disease respond to treatment.

For example and to establish definitions.

• “In patients with atypical Crohn’s disease features, … prognosis can be remarkably favorable upon oral treatment with cyclophosphamide.” [2016] – this has high toxicity.
• A Case of Intestinal Mastocytosis Misdiagnosed as Crohn’s Disease [2015]. This is too many mast cells producing too much histamine.

This is a nice study,  The Treatment-Naive Microbiome in New-Onset Crohn’s [2014] Disease which shows a both any treatment and what happens with treatment with an antibiotic.

Note some factors shared with CFS and FM microbiomes:

• Major decrease if bifidobacteria [Kyberompact Post]
• Increase of Enterobacteriaceae as seen with IBS  [2016]

The differences:

• Pasteurellacease are normal or low in CFS [Post], high in Crohn’s disease
• Fusobacteriaceae are normal in CFS, high in Crohn’s disease
• Some species of Veillonellaceae  are low in CFS [post], the entire group is high in Crohn’s disease

The two biggest shifts (the biggest increase and the biggest decrease) in Crohn’s disease are also seen with CFS.  The difference is that other families have not shifted yet. How the body responds to further shifts is influenced by DNA.

This study also illustrate the effect of antibiotics — they appear to make the total shift worst (but may result in some symptom relief).

Bottom Line

As I wrote earlier: Autoimmune = DNA + Microbiome shift. The more that shifts, the worst the autoimmune condition can become. Which autoimmune disease is likely a function of your DNA. If you are unlucky, you may end up with several pages of diagnosis.  The final problem is how to shift the microbiome back to normal. The first step is to inhibit further shifting: for CFS, given what is available, it appears to be E.Coli probiotics and bifidobacteria probiotics as a starting point.