Review on Metabolome and Bacteriophages Research

This last week there were two very interesting studies published:

 

Metabolome Study

  • Patients were a very specific subset of CFS patients (“met diagnostic criteria for ME/CFS by Institute of Medicine, Canadian, and Fukuda criteria.” – i.e. 3 different criteria )
  • “Patients with CFS showed abnormalities in 20 metabolic pathways. Eighty percent of the diagnostic metabolites were decreased”
    • Male abnormalities were:
      • Sphingolipids
      • Glycosphingolipids
      • Phospholipids
        • “a very specific molecular species of phospholipid, PC(18:1/22:6), containing the essential omega 3 fatty acid docosahexaenoic acid (DHA, C22:6) and oleic acid (C18:1) was increased.”
      • P5C, Arg, Ornithine, Pro
      • Cholesterol, nongonadal steroids
      • Branch chain amino acids (different in males and Females)
      • Purines
      • Microbiome metabolism
      • Vitamin B2 (riboflavin) – this is a component of d-ribose which is known to help CFS
      • Serine, 1-carbon metabolism
      • SAM, SAH, methionine, glutathione
      • Very long chain fatty acid oxidation
      • Propiogenic amino acids
      • Threonine metabolism
      • Fatty acid oxidation and synthesis
      • Collagen/hydroxyproline metabolism
      • Bile salt metabolism
      • Endocannabinoids (Females only)
      • Vitamin B12 (cobalamin) metabolism (Females only)
      • Amino-sugar, galactose, and nonglucose (Females only)
  • “the metabolic features of CFS are consistent with a hypometabolic state.”
    • From 1959: “The most common signs and symptoms of hypometabolism were chronic fatigue, enlarged thyroid gland, gynecologic disorders, dry hair, and nervousness and irritability. The most frequent gynecologic disorders were adnexal congestion, pelvic pain, adnexal tenderness, and menstrual irregularity.”

I am not going to dive into each and every item above. With the above metabolites (chemicals) being low then supplementation should reduce symptoms – remember we are talking about chemicals produced by cells and bacteria. In fact, we know that B12 and B-2 (via d-ribose) does that.

What I find  interesting is Microbiome metabolism. “Aromatic Amino Acid Metabolites from the Microbiome Were Decreased….this pattern is also opposite of what is found during acute inflammation and infection “. Metabolites ” have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, catalytic activity of their own (usually as a cofactor to an enzyme), defense, and interactions with other organisms (e.g. pigments, odorants, and pheromones).”  Metabolites are produced by cells, including bacteria in the microbiome.

Illustration:

In short — a change of metabolism can clearly be associated with a shift of bacteria in the microbiome. Different bacteria will produce different metabolites.

Questions and Answers

  • Can this be used to give a CFS diagnosis?
    • No. This allows a group of CFS patients and healthy controls to be classified. These tests may fail to tell the difference between diabetes and CFS, or migraines and CFS, IBS and CFS, UC and CFS, Crohn’s Disease and CFS, Hypothyroidism and CFS,  etc. For example, Alzheimer’s Disease had hypometabolism also. [2008]

      Further studies are needed to see if it can tell the differences between different diseases that are associated with hypometabolism.

  • Can this be used to exclude CFS?
    • Not with absolute certainty … The test is 90-95% accurate, i.e. 1 in 10 CFS patients will return a false negative.
  • What are positive conclusions?
    • CFS should not be viewed as “acute inflammation and infection” and treatment assuming that, may be counter productive
    • Supplementation for items that are low may result in symptom reductions.
  • The findings on DHA suggests we should not supplement with it?
    • There are two studies on levels and no studies on trying it as a treatment. Personally, I would not.
      • [2003] “found that the levels of … docosahexanoic acid (DHA) were decreased in patients suffered from CFS. However, the levels of the palmitic acid and oleic acid were increased.”
      • [2005] which look at the general levels
  • Does this finding agree with your model?
    • Yes — what is being measured is what is being produced by bacteria and cells. Thus a change of bacteria would result in a change of metabolites.

Bacteriophages Study

see NPR Your Gut’s Gone Viral, And That Might Be Good For Your Health (with audio)

The common (and incorrect) attitude is that all virus are bad.

  • “From the combined group of people, Young and his team identified 23 bacteriophages that seemed to be associated with a healthy gut. These viruses were common in more than half the healthy people and were much less common in people with Crohn’s or colitis”
  • “Some scientists suspect bacteriophages may determine which bacteria get to dwell in the gut and which ones aren’t allowed to stay, Eisen says. Bacteriophages are potent assassins.”

So one day, we may see capsules of virus being used to treat the microbiome dysfunction seen in CFS, IBS, etc — until that day, the best hope is snogging with healthy young people 🙂 — transfer their healthy bacteria and virus!

 

Survey Results on Adaptogens

As usual, the numbers of responses are low. We work with what we have. I have updated the earlier results for herbs and antibiotics (no major changes).

Adaptogens as a category does not seem to shine.  Licorice and Neem are still the preferred ones in the category of Adapatogens. They have other effects beyond being adaptogens.

You may add your experience with this survey(CLICK HERE TO DO SURVEY).

You want to start with the LOWEST RISK Ratios between benefit and risk. Neem and Ashwagandha are the leaders.

Nov 23 2016

Severe Herx Significant Worst Worst No Change Better Significant Better Have Not Tried Total Odd of Better Odds of Worst Risk Ratio
Rosavin(Rhodiola rosea) 0 1 0 3 3 0 8 15 43% 14% 0.33
Siberian Ginseng AKA Eleuthero(Eleutherococcus Senticosus) 0 0 1 4 1 0 9 15 20% 20% 1.00
Ashwagandha (Withania somnifera) 0 0 1 1 4 3 6 15 78% 11% 0.14
Dang Shen (Codonopsis pilosula, C. tangshen) 0 0 1 0 0 0 12 13 0% 100% HUGE
 Jiaogulan (Gynostemma pentaphyllum) 0 0 0 2 0 0 13 15 0% 0% Unknown
American Ginseng (Panax quinquefolius) 0 0 1 2 0 0 11 14 0% 33% #DIV/0!
Asian Ginseng (Panax ginseng) 0 0 1 2 2 0 9 14 25% 25% 1.00
 Reishi Mushroom akalingzhi mushroom(Ganoderma ludicum) 0 1 1 2 1 0 11 16 25% 50% 2.00
 magnolia-bark(Magnolia officinalis) 0 0 0 0 0 0 14 14 #DIV/0! #DIV/0! Unknown
Jujube(Ziziphus jujuba) 0 0 1 0 0 0 12 13 0% 100% Huge
Licorice 0 0 1 3 5 2 5 16 60% 10% 0.17
Neem 0 0 0 1 4 2 8 15 56% 11% 0.20

What does antibiotics/herb X kill?

A reader asked “My question is, do you have any source where it shows which strain does the allicin(garlic) kill?”

I will answer this question by showing the steps that I took to answer it.

  1. https://www.wikipedia.org/ and enter the name – you want to get the various brand names that it may have. In this case it is easy: {garlic,allicin}
  2. Go to PubMed. and start with a wide search:
    1. (garlic OR allicin) and bacteria
  3. My results had over 600 hits.
  4. Start scanning the titles and making notes, I usually add the Uri to the article for future reference, often the title is enough, sometimes opening the links will get good details.

General Results

Specific Results

If you want to know if it will impact Lactobacillus bacteria (i.e. probiotics):

(garlic OR allicin) and lactobacillus

which returned 37 hits.

  • “The inhibition zones of the different concentrations of garlic extract were not significantly different for S. mutans, S. sanguis, and S. salivarius. For P. aeruginosa and lactobacillus spp. the inhibition zones of 5%, 10% and 20% concentrations were not significantly different from one another,” Antibacterial effect of different concentrations of garlic (Allium sativum) extract on dental plaque bacteria.
  • Effect of garlic powder on the growth of commensal bacteria from the gastrointestinal tract. “While for most bacteria the antimicrobial effect was transient, the lactobacilli showed a degree of resistance to garlic, indicating that its consumption may favour the growth of these beneficial bacterial species in the gut. Garlic intake has the potential to temporarily modulate the gut microbiota.”
  • “The impact of these extracts on the growth of selected probiotic bacteria (Lactobacillus reuteri, Lactobacillus rhamnosus, Bifidobacteria lactis) and pathogenic bacteria (Escherichia coli 0157:H7 and Escherichia coli LF82) was assessed using a standard minimum inhibitory concentration method. The results showed that aqueous extractions of garlic and black peppercorns significantly enhanced the growth of one strain of probiotic bacteria (L. reuteri) whilst inhibiting both pathogenic strains of E. coli at a 1:50 dilution.” In vitro effects of food extracts on selected probiotic and pathogenic bacteria.

No results can happen

Since   is high in CFS and is also associated with histamine production,  I tried the following search:

(garlic OR allicin) and Morganella

There were no results.

August Review of News on Probiotics

I follow a few groups that deal with probiotics in general. This is my periodic extract of interesting random notes, sometime with slightly off the wall comments (to get people thinking!”

  • “humans harboring a type of Staphylococcus bacterium-S. lugdunensis-in their noses have a lower abundance of S. aureus, the kind that can cause nasty infections.” [Scientific American]  “First we had shyte transplants, now we are heading to nose goobers transplants!”. Actually only 20% were found to have this bacteria. Coming soon — nasal probiotic sprays!
  • “Nail-Biters, Thumb-Suckers Have Fewer Allergies … “The findings support the ‘hygiene hypothesis,’ which suggests that being exposed to microbes as a child reduces your risk of developing allergies….  a set of articles published this month in Perspectives in Public Health takes issue with the idea that modern ideals of cleanliness are harming our health, arguing that this view hinders efforts to combat the rise in allergies and chronic inflammatory diseases. “[the Scientist]
  • “Kids often acquire cavity-causing bacteria from non-family members, researchers report at the American Society for Microbiology annual meeting.” [The Scientist]
  • “Food that travels faster through the gut results in bacteria producing less harmful by-products in the digestive system, resulting in a healthier gut environment, according to a study…. diet rich in fiber and plenty of water” [Nature]
  • “Vitamin D3 may increase bacterial richness in the upper gastrointestinal tract and reduce opportunistic pathogens, says a new study from Austria.” [European Journal of Nutrition]
  • “Certain food additives may interfere with your gut bacteria, causing changes that boost inflammation in the intestines and potentially promote the development of some chronic diseases, a new study suggests. In the study, researchers looked at ingredients called emulsifiers, which are added to many processed foods, including ice cream and peanut butter,”[Transactional Microbiome]
  • “While there is some evidence from previous reviews that probiotic interventions may benefit those with disease-associated imbalances of the gut microbiota, there is little evidence of an effect in healthy individuals.” [Genome Medicine]
  • “Intestinal bacteria that can boost bravery or trigger multiple sclerosis: An increasing body of research results confirms the importance of the “gut-brain axis” for neurology and indicates that the triggers for a number of neurological diseases may be located in the digestive tract.” [European Academy of Neurology]
  • “Metagenomic profiling revealed that the low-dose chemical exposure resulted in significant changes in the overall bacterial composition, but in adolescent rats only. Specifically, the individual taxon relative abundance for Bacteroidetes (Prevotella) was increased while the relative abundance of Firmicutes (Bacilli)was reduced in all treated rats compared to controls. Increased abundance was observed for Elusimicrobiain DEP and MPB groups, Betaproteobacteria in MPB and MIX groups, and Deltaproteobacteria in TCS group. Surprisingly, these differences diminished by adulthood (PND 181) despite continuous exposure, suggesting that exposure to the environmental chemicals produced a more profound effect on the gut microbiome in adolescents.” [Microbiome]
  • “Probiotic strain Lactobacillus gasseri activates ‘multiple actions’ that may work in synergy to prevent obesity, Japanese research in rats has suggested.” [British Journal of Nutrition]
  • “Frailty (old age) was associated with species and genus abundance. Species more abundant with frailty included Eubacterium dolichum and Eggerthella lenta. Also, Faecalibacterium prausnitzii was less abundant in frailer individuals.” [Gut Microbiota]
  • “Mice raised under specific pathogen-free conditions in a lab do not model the natural exposure of animals and humans to environmental commensals and pathogens. Now, two studies show that exposing mice to their natural environment, or infecting them with specific pathogens, results in an immune system that better resembles that of adult humans.” [Nature] — i.e. many studies with mice may yield  misleading or even false results.
  • “The absence of one specific bacterial species[Lactobacillus Reuteri] in the gut is associated with the development of social behaviour that falls within a range of autism spectrum disorders (ASDs), according to a study in mice.” [Economist]
  • “Primates, Gut Microbes Evolved Together” [The Scientist] “When the researchers compared the phylogenetic trees of hominids to the trees of the bacterial species from the fecal samples, they found that both trees reflected the same evolutionary branching. In other words, most of the bacterial species in humans were not found in the ape samples. The researchers saw that for two of the three bacterial families, species were clearly present only in one modern day hominid, suggesting a distinct co-evolution for two of the three bacterial families with their hosts.” This echo my belief that your personal DNA and your personal gut bacteria have evolved together.
  •  “This study demonstrated that increased intestinal permeability [leaky gut] may be induced by bacteriophages that affect the microbiota.” [Gut Pathogens] The ” bacteriophage cocktail was active againstStaphylococcus spp., Streptococcus spp., Proteus spp., Pseudomonas spp., E. coli, K. pneumonia, andSalmonella spp”; i.e. the body response to the above infections (creating bacteriophages) may induce leaky guts in some as a side effect. Removal of those infections would stop the production of bacteriophages  and thus could heal leaky guts.
  • “We further showed that there were 7 (3 negative and 4 positive correlation) OTUs significantly correlated with all the three types of cognitive abilities, at the order level, including Bacteroidales, Clostridiales, Desulfovibrionales,..” [Journal of Alzheimer’s Disease]
  • “found that inducing strokes in mice altered the animals’ gut microbiota, triggering an immune response that traveled back to the brain and worsened the severity of the lesions.” [The Scientist]
  • “Compared with untreated mice, adult mice treated with antibiotics showed significantly fewer newly formed brain cells (i.e. reduced neurogenesis) in the hippocampus region of the brain, and subsequently their memory also deteriorated ..it has been previously reported that antibiotic-induced gut dysbiosis may lead to impaired cognition in mice, little is known about the link between the brain, the local and systemic immune system, and the gut microbiota. ” [Gut Microbiota]
  • In “the healthy control group. Bacteroides, Proteobacteria, and Actinobacteria increased in level, whereas that of Firmicutes was reduced in major depressive disorder groups compared with the healthy control group.” [Gut Microbiota]
  • “intestinal microbiota changes promote a pro-inflammatory environment in systemic lupus erythematosus SLE patients…it has been found that enriching SLE gut microbiota with two Clostridia strains (Ruminococcus obeum DSM25238 and Blautia coccoides DSM935) along with Bifidobacterium bifidum LMG13195, which have a Treg-inducing function, reduced the Th17/Th1 balance and prevented Th over-activation. [Gut Microbiota]

 

Clinical Guide to Probiotic Products in US

It is interesting to note that Mutaflor (E.Coli Nissle 1917) is included in the list.

These lists studied probiotics for various conditions and the degree of evidence supporting the conditions that they help.

  • Infections diarrhea aka ID
  • Antibiotic associated diarrhea – Prevention aka AAD
  • Clostridium Difficile associtaed diarreha – Prevention aka CDAD
  • Traveler’s diarrhea aka TD
  • Constipation aka C
  • Functional abdominal pain aka FAP
  • Irritable bowel syndrome aka IBS
  • Ulcerative colitis – Adjunct to standard therapy aka IBD-UC
  • Inflammatory bowel disease – Pouchitis aka IBD-P
  • Heliobacter pylori – Adjunct to standard eradication therapy aka HP
  • Oral health aka OH
  • Reduction of LDL and total cholesterol aka LDL-C
  • Common infectious disease aka CID

With the degree of evidence supporting their use.

Guides are available for:

There is also, “A Gastroenterologist’s Guide to Probiotics” with an audio pod cast.