Overview of this Blog and the Microbiome

My ideas on this blog have evolved, as more and more information becomes available. This post is an attempt to bring readers up to date with my current thinking. I am striving to be transparent in my logic — showing the evidence I am working from, and my thought processes.


Notes to Treating Physicians     Quick Self Start on treating CFS


Analysis of Microbiome/stool with recommendations

Site: has moved to http://microbiomeprescription.azurewebsites.net

The data is available in an online collaborative python workbook for analysis. See this post.


Microbiome Definition of CFS/FM/IBS

A coarse condition that results from:

  • Low or no Lactobacillus, AND/OR
  • Low or no Bifidobacteria , AND/OR
  • Low or no E.Coli , AND/OR
  • A marked increase in number of bacteria genus (as measured by uBiome) to the top range
    • Most of these genus are hostile to/suppress Lactobacillus, Bifidobacteria, E.Coli
    • Several are two or more times higher than normally seen
    • The number of bacteria genus goes very high (using uBiome results), but most of them are low amounts.
      (“Death by a thousand microbiome cuts” and not “Death by a single bacteria blow”)
  • The appearance of rarely seen bacteria genus in uBiome Samples.

A finer definition would be a condition with a significant number of abnormalities in the ‘Autoimmune profiles see this page for the current criteria (i.e. over 25%).

The specific genus and their interactions determine the symptoms seen — likely due to the over- or under-production of metabolites (chemicals). Other autoimmune conditions may share these core shifts. The specific high and low bacteria determine the symptoms if the person was the DNA/SNP associated with the symptoms.

Replace the metabolites produced by the missing bacteria

Replacing the metabolites should result in the reduction of symptoms associated with a deficiency of these metabolites.

See this post for the study references. These items should/could be done continuously.

Other Supplements Reported to Help

Bootstrapping Bifidobacterium and Lactobacillus

The items below were found in studies to increase bifidobacterium and lactobacillus:

Unless the bifidobacterium and lactobacillus (B&L) are human sourcedthere is almost zero chance of taking up residency. Taking probiotics will not allow B&L to get established. In fact, there are grounds to believe that most commercial probiotics actually reduce your  native B&L. You want to encourage your native B&L. See this post for citations.

Bootstrapping E.Coli

The E.Coli probiotics below are human sourced and known to take up residency in the human gut.

  • Core: D-Ribose a preferred food that it uses
  • Mutaflor probiotics — E.Coli Nissle 1917
  • Symbioflor 2 — multiple strains

Dealing with the other microbiome shifts

The other microbiome shifts appear to be in different clusters of microbiome shifts. This 2017 paper by Peterson, Klimas, Komaroff, Lipkin (and a stack of other CFS researchers) makes that clear in its title: “Fecal metagenomic profiles in subgroups of patients with myalgic encephalomyelitis/chronic fatigue syndrome”.

The best way at present to proceed is to order an analysis from uBiome. (Disclosure: I have no financial interest in this company.) When your get your results back, log in, click on the “Compare” tab, then go to “Genus,” and click on “ratio” twice, so the results are in descending order.

This is the “hit list” of what you are trying to reduce. DataPunk provides a nice summary of what we know about these. See, for example, Alistipes:

At this point, we run into a logistical challenge.  You want to avoid items that are “Enhanced By” (which is in common across all of the high items) and take the items that are “Inhibited By” (which are not on any of the “Enhanced By” lists).  You may also wish to reduce foods that are high in items listed in “Nutrients/Substrates.”  It becomes a jig-saw puzzle! I have done this exercise for many readers’ uBiome results:

I have discovered that DataPunk is not absolutely current, and have started creating posts based on its data, and then added studies from 2016 and 2017 to the page. Past pages are below, for current list MicrobiomePrescription site.

nihms-731256-f0001

Src: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4754147/

General Suggestions (no uBiome results)

Some of these items are contraindicated with a few uBiomes that I have reviewed. This likely is why person B reports no results while person A reports improvement. Example: Magnesium is usually very helpful — but there are a few cases where it encourages overgrowth of undesired  bacteria.

Probiotics

Most probiotics do not take up residency. They are “here today, gone tomorrow”. Their primary role in my model is producing natural antibiotics against other bacteria. For example:

Probiotics should be rotated: 2 weeks on a specific one, then several weeks off. As a general rule, you want about  6-12 B CFU taken three times a day (or 2-3 times the recommended dosage) — but work up slowly because you may get be a major herx! In general, do not take Lactobacillus with Bifidobacteria or with E.Coli etc. Keep to one family per cycle. You do not want them to kill off one another!

Why 3x per day? Because almost none of them are detected after 12-24 hrs. So to keep them — and the production of natural antibiotics — going, you need to keep taking them during the day. See this post for citations.

The following probiotics commonly seem to help people with CFS/Lyme/Fibro:

Some probiotics, however, may make your symptoms worse! And, unfortunately, most commercial probiotics contains some of these. At the moment Bifidobacterium animalis, Saccharomyces boulardii and Lactobacillus acidophilus are on my best to totally avoid list.

  • “. The findings show that the six species of Bifidobacterium differed in their ability to relieve constipation. B. longum, B. infantis and B. bifidum were the most effective in relieving constipation, B. adolescentis and B. breve were partially effective and B. animalis was not effective. Furthermore, edible Bifidobacterium treated constipation by increasing the abundance of Lactobacillus and decreasing the abundance of Alistipes, Odoribacter and Clostridium. .” [2017]

On my neutral list (no clear benefit) is Lactobacillus Plantarum.

Teas

Some teas can also be antibiotics (among other roles). There are two teas that seem to produce significant results quickly:

Again, rotate and, if practical, change brands too. Their antibiotic compounds are different from different sources.

Herbs and Spices

The best choice needs examination of your microbiome (i.e. uBiome results) and doing the work cited above.  Survey results found:

  1. Neem and Oregano with 80% improving
  2. Olive Leaf and Licorice with 56% improving
  3. Thyme with 50% improving
  4. Wormwood and Tulsi with 33% improving

Other things

If you do not know your microbiome, then see https://cfsremission.com/reader-surveys-of-probiotics-herbs-etc/  for suggestions. Your results will vary because your microbiome vary.

Thick blood is an issue also — but here things gets more complicated and not suitable for this recap.

Antibiotics can have a role — but getting prescriptions for the right ones can be a major challenge.

Metabolism Shifts

From volunteered data, we can identify some distinctive shifts, see Metabolism Explorer Summary

Bottom Line

Working with the microbiome and autoimmune is like working with fragments of the dead sea scrolls. For many bacteria we can identify it — what inhibits or encourages it is not known to modern medical science.  We have extremely thin slices of knowledge –Almonds enhances Bifidobacterium, Lactobacillus (B&L)  as do sesame seeds. What about sunflower seeds? Peanuts? Cashews? We find that Walnuts help the bacteria that inhibits B&L — so we cannot safely generalize to “all seeds/nuts are helpful”.

In many cases, we find that healthy diet or supplements demonstrated to work for normal people have the opposite effect on CFS and other altered microbiome conditions. This is made even worst because most of the studies were done on males and most people with CFS are females. We end up having to swim up-stream thru good and valid suggestions — that are just wrong for us.

My model is simple to understand and allows us to filter many suggestions and candidates. With the availability of uBiome testing (without needing a prescription!) we have entered the age of explicit treatment based on your unique microbiome. We do not know the role of many bacteria involved. We do not know what will inhibit or enhanced all of these bacteria. Frustrating little knowledge!

On the flip side, many readers have reported significant improvement, reduction of prescription medication, etc. so the model and suggestions have potential and thus hope of remission! Microbiome studies are exploding on PubMed, a lot of research is being done and we can often borrow their results.

This is an education post to facilitate discussing this approach with your medical professionals. It is not medical advice for the treatment of any medical condition. Always consult with your medical professional before doing any  changes of diet, supplements or activity. Some items cites may interfere with prescription medicines.

Some sources to consider for probiotics

A reader wrote:

I’d like to do:
  • Lactobacillus Fermentum ME3
  • Lactobacillus Kefiri LKF01
  • Lactobacillus Reuteri
  • Lactobacillus Casei
  • Bifidobacterium infantis
  • Bifidobacterium Longum
  • Bifidobacterium bifidum
  • Bifidobacterium Breve
But I don’t find them isolated. 😦
As readers know — I tend to look unfavorably on both probiotics mixtures and probiotics that lacks strain information. If the probiotic source is not human, there is a very low chance that they will take up residency (Soil Based Organism are the probable exception)
The sources that I know of for these are:

Custom Probiotics provide strain information, including the ATCC number.

Note: they may not be available in the country you are in. I have faced that issue often. My past solution is to get an online friend to forward them to you and you buy them and get them delivered to their address, they then forwards as “Gift – probiotics” for customs.

The other option is looking on eBay – the vendors there tend to ignore any government regulations that prevents regular outlets from stocking them or shipping to your location.

Reducing the risk of C. difficile while on antibiotics

A reader is dealing with an antibiotic resistant abscess which have kept recurring after several courses of different antibiotics. She wrote because the latest escalation had a risk of  C. difficile. Actually, it is Peptoclostridium difficile  and not Clostridium difficile, because it has been recently reclassified.

The first harsh reality is that 55% of people have some of this bacteria…. so the issue is whether this bacteria will seize the opportunity to expand to clinically significant levels.

  • “Clostridium difficile is the leading infectious cause of antibiotic-associated diarrhea and colitis. C. difficile infection (CDI) places a heavy burden on the healthcare system, with nearly half a million infections yearly and an approximate 20% recurrence risk after successful initial therapy. ” [2018]
  • “Probiotic use did not appear to attenuate the odds of CDI in patients exposed to high-risk antibiotics, but moderate-risk antibiotics appeared to significantly attenuate the odds of CDI in patients who received probiotics.” [2018]
    • “From the perspective of the medical system, oral probiotics as a preventive strategy for CDAD in hospitalized children and adolescents receiving a therapeutic course of antibiotics reduced the risk of CDAD and represents a cost-saving strategy.” [2018]
  • ” C. difficile infection incidence in the United States has increased dramatically since 2000. In the United States ” [2018]
    • “Outbreaks of hypervirulent strains of Clostridium difficile began to be reported in healthcare facilities worldwide around 20 years ago. Concurrently, trehalose became a common additive used by the global food industry. A new study provides evidence that these two observations are a linked phenomenon [2018]

Using the http://microbiomeprescription.azurewebsites.net site, we find that the following reduces this bacteria according to studies:

And the following should be avoided:

Bottom Line

A sugar-free (or at least reducing sugar content) diet is the first suggestion. Increased vitamin B supplementation and melatonin is also suggested. Adding 1-3 bananas a day may also be beneficial as well as making food from scratch (i.e. no prepared foods due to trehalose additives). Evidence for probiotics is generally deemed weak in all of the latest studies.

NOTES:

  • On prepared foods, trehalose may not be explicitly labelled, rather included under “sugar”.
  • Trehalose occurs naturally in small amounts in mushrooms, honey, lobsters, shrimps, certain seaweeds (algae), wine, beer, bread and other foods produced by using baker’s or brewer’s yeast [3].
  • Trehalose is heat stable and preserves the cell structure of foods after heating and freezing, so it is used as a food texturizer and stabilizer in dried foods, frozen foods, nutrition bars, fruit fillings and jams, instant noodles and rice, white chocolate, sugar coating, bakery cream, processed seafood and fruit juices [3,4].

 

 

Drug Effectiveness and the microbiome

A reader wrote about how a prescription drug effect on her varied greatly day by day. I recall that the microbiome can vary greatly day by day (from charts on http://richardsprague.com/ ). I thought I should visit this topic.

Many people know that grapefruit interacts with many drugs.

 

Microbiome and Diet

Diet

Diet impacts the microbiome, whether the effects below are independent of the microbiome or due to temporal changes of the microbiome is unknown.

  • Influence of diet and nutritional status on drug metabolism [1996].
    • ” It is well known that smoking, charcoal broiled food or cruciferous vegetables induce the metabolism of many xenobiotics, whereas grapefruit juice increases the oral bioavailability of the high clearance drugs nifedipine, nitrendipine or felodipine by inhibiting their presystemic (intestinal) elimination. Energy deficiency, and especially a low intake of protein, will cause a decrease of about 20 to 40% in phenazone and theophylline clearance and elimination of those drugs can be accelerated by a protein-rich diet. In the same way, protein deficiency induced by either vegetarian food or undernourishment will have the opposite pharmacokinetic consequences.”
  • ” Feeding rats brussels sprouts or cabbage stimulates the intestinal and hepatic metabolism of drugs in animals. This effect is caused, at least in part, by certain indoles normally present in these vegetables. The feeding of a charcoal-broiled beef diet to rats stimulates the metabolism of phenacetin in vitro, and a similar diet stimulates the in vivo metabolism of phenacetin in man” [1977]
  • “Several dietary factors influence the oxidative metabolism of chemicals in humans. Increasing the ratio of protein to carbohydrate or fat in the diet, feeding cabbage and brussels sprouts or feeding charcoal-broiled beef for several days stimulates human drug metabolism. The chronic ingestion of ethanol stimulates drug metabolism whereas the chronic ingestion of methylxanthine-containing foods inhibits drug metabolism. In contrast, an increase in the ratio of fat to carbohydrate in the diet of normal subjects or the fasting of obese individuals for several days has little or no effect on drug metabolism. Flavonoids in edible plants influence the metabolism of foreign chemicals by human liver in vitro. The addition of flavone, tangeretin or nobiletin to human liver microsomes activates both the hydroxylation of benzo[alpha]pyrene and the metabolism of aflatoxin B1 to mutagens. On the other hand, quercetin, kaempferol, morin and chrysin, which are also normally occurring flavonoids, inhibit the hydroxylation of benzo[alpha]pyrene by human liver microsomes.” [1980]

Microbiome

  • “These data clearly illustrated that gut microbiome phenotypes significantly affected arsenic metabolic reactions, including reduction, methylation, and thiolation. These findings improve our understanding of how infectious diseases and environmental exposure interact and may also provide novel insight regarding the gut microbiome composition as a new risk factor of individual susceptibility to environmental chemicals.” [2013] – likely applies to pharmaceutical chemicals also.
  • “The influence of our microbiota reaches from primary metabolites to secondary effects such as substrate competition or the activation of eukaryotic Phase I and Phase II enzymes. Further on it plays a hitherto underestimated role in drug metabolism, toxicity and pathogenesis.” [2015]
  • Metabolism by the intestinal microbiota might result in a different metabolite profile than that produced by host tissues. This could potentially result in either activation or inactivation of the pharmacological and/or toxicological actions of the compound in question. The contribution of the intestinal microbiota to drug metabolism remains relatively unexplored.” [2013]
  • ” Given that the interplay between the gut microbiota and host cells is likely subject to high interindividual variability, this work has tremendous implications for our ability to predict accurately a particular drug’s pharmacokinetics and a given patient population’s response to drugs.” [2015]
  • A specific example of a bacteria strain that predict cardiac drug metabolism [2017]

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Bottom Line for Drug Effectiveness

If a drug has no effect on Monday, it may be effective a week or month later. The cause may be due to diet and/or microbiome (which can be influenced by diet). Welcome to the complexity of human health!

If a drug does not have the desired effect, consider a change of diet, supplements and herbs for 1-2 weeks and then try again.

Enteragam – another medical food

2-FL (Human Milk Oligosaccharides) is a medical food which I wrote about in this August 2018 post. A reader ask for my thoughts on Enteragam, another prescription medical food. It’s Serum-derived bovine immunoglobulin/protein isolate

A general introduction to the topic of medical foods can be find in

The Emerging Therapeutic Role of Medical Foods for Gastrointestinal Disorders[2017].

  • “A medical food, according to the FDA, is a food that is developed to be eaten or administered enterally under the guidance of a physician and that is meant for the specific dietary management of a condition or disease for which distinctive nutritional requirements, based upon known scientific principles, are established by medical evaluation.

Current and emergent pharmacologic treatments for irritable bowel syndrome with diarrhea: evidence-based treatment in practice[2017].

The US distributor describes is as:

“EnteraGam® (a serum-derived bovine immunoglobulin/protein isolate, SBI) is a medical food product intended for the dietary management of chronic diarrhea and loose stools. EnteraGam® must be administered under medical supervision. EnteraGam® binds microbial components, such as toxic substances released by bacteria, that upset the intestinal environment. This helps prevent them from penetrating the lining of the intestine, which may contribute to chronic diarrhea and loose stools in people who have specific intestinal disorders.”

SBI

 

So, what is published about it?

Bottom Line

. This is a promising medical food that may have implications across most of the conditions that I tend to look at. The absorption of toxins from bacteria makes it a universal treatment candidate.

If you have an opportunity to try it, I would recommend the experiment (and ideally reporting back here after 30 days).

A similar product (non-prescription)

Note: No explicit pubmed studies found on this product. It is also just one type of immunoglobulin.

SBI Protect Capsules

SBI Protect is the only purified, dairy-free source of immunoglobulin G (IgG) available as a dietary supplement. Pure IgG helps to maintain a healthy intestinal immune system by binding a broad range of microbes and toxins within the gut lumen.

SIBO Testing with Lactulose

“The findings of the lactulose breath test in irritable bowel syndrome patients have been used to suggest that most patients have small intestinal bacterial overgrowth (SIBO), and this association has spawned the widespread use of antibiotics in IBS. The study by Bratten and colleagues demonstrates that this test does not discriminate between IBS patients and healthy controls when criteria from recent clinical IBS studies are applied. ” [2008]

I recently added some more studies and found that the list of bacteria that will consume lactulose is quite large — with both good and bad listed.

Taxonomy Rank Effect
Bifidobacteriaceae family Increases
Lactobacillaceae family Increases
Streptococcaceae family Increases
Bifidobacterium genus Increases
Lactobacillus genus Increases
Lactobacillus genus Increases
Streptococcus genus Increases
Streptococcus genus Increases
Aerococcus viridans species Increases
Bacteroides fragilis species Increases
Bacteroides ovatus species Increases
Bacteroides thetaiotaomicron species Increases
Bacteroides uniformis species Increases
Bacteroides vulgatus species Increases
Bifidobacterium adolescentis species Increases
Bifidobacterium bifidum species Increases
Enterobacter aerogenes species Increases
Enterococcus faecalis species Increases
Escherichia coli species Increases
Lactobacillus acidophilus species Increases
Lactobacillus brevis species Increases
Lactobacillus casei species Increases
Lactobacillus rhamnosus species Increases
Parabacteroides distasonis species Increases
Peptoclostridium difficile species Increases
Peptostreptococcus anaerobius species Increases
Proteus mirabilis species Increases
Proteus vulgaris species Increases
Streptococcus thermophilus species Increases

Bottom Line

Recently I posted about another probiotic that gave positive lactulose breath test when given to healthy individuals. I look at the list above and see many bacteria that are often in yogurt or available as probiotics.

In short, not only have studies on human discredited this test — but logic also discredit it. It is totally unclear which bacteria is overgrown!

Probiotics News – June 2018

This is a continuation of my trying to get caught up on reviewing interesting news. Sometimes a new dimension appears that results in enhancements of the analysis site; other times, it is just interesting events happening. The quality of the items can be questionable (marketing literature), often the reviews reveal some interesting gems.

 

  • Gigantic study of Chinese babies yields slew of health data
    “The Chinese team has so far avoided similar problems. Its rich collection of 1.6 million biological samples includes specimens of stools, blood, placental tissue and umbilical cords. Extensive surveys also record participants’ eating habits, mental health, and other lifestyle factors, such as the amount of mould in their house.”
  • “Gut microbiota modulate neurobehavior through changes in brain insulin sensitivity and metabolism”[src]
  • ‘Social microbes’ critical to brain development…Absence linked to reduced sociability in people with autism spectrum disorders”[src]
  • From src
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  • PowerPoint ?????????
  • nha-4-nha170030-g003
  • nha-4-nha170030-g004
  • Designing large-scale gut microbiome studies – 10 essential considerations<http://blog.dnagenotek.com/microbiome/designing-large-scale-gut-microbiome-studies-10-essential-considerations>
  • An analysis of faecal metabolites ( molecules in stool produced by microbes) found that less than a fifth (17.9 per cent) of gut processes could be attributed to hereditary factors, but 67.7 per cent of gut activity was found to be influenced by environmental factors, mainly a person’s regular diet. [src]
  • Triclosan (TCS) is a high-volume chemical used as an antimicrobial ingredient in more than 2000 consumer products, such as toothpaste, cosmetics, kitchenware, and toys. We report that brief exposure to TCS, at relatively low doses, causes low-grade colonic inflammation, increases colitis, and exacerbates colitis-associated colon cancer in mice. Exposure to TCS alters gut microbiota [src]
    • “Triclosan exposure is practically unavoidable in the United States, but little is known how ingestion may affect our health” [src]
    • Why Is Triclosan in Toothpaste? [Consumer Reports]

  • Bacteria Survive in NASA’s Clean Rooms by Eating Cleaning Products [src]
  • When three groups of mice received a custom diet supplemented with porphyrin-rich seaweed (a kind of microbiota-accessible carbohydrate (MAC) found in nori) seven days after inoculation with B. ovatus NB001, a robust increase of up to six orders of magnitude was detected in the strain’s density in feces, irrespective of background microbiota.  [src]
  • As reported on November 17, 2017 a randomized, double-blind, placebo-controlled study in 90 older women showed that supplementation of the probiotic strain Lactobacillus reuteri ATCC PTA 6475 decreased bone loss compared to placebo [src]
  • Daily supplementation with the probiotic strain Bacillus subtilis C-3102 may improve stool frequency and consistency in healthy people, says a new study. [src] always note the “may” is not a “will”/ Speculation
  • Researchers from Japan are using the findings of studies on centenarians in the country to try and produce new products that will replicate the beneficial aspects of their microbiota. [src]
  • Here we report that our routine use of mock communities as internal standards allowed us to discover highly aberrant and strong biases in the relative proportions of multiple taxa in a single Illumina HiSeqPE250 run. [src]
  • No clear evidence probiotics can help with human anxiety, study finds
  • The University of Otago, Christchurch, researchers found a toxic form of a bacteria called Bacteroides fragilis in the gut of almost 80 percent of people with a pre-cancerous lesion — a precursor to the disease.[src]
  • Dr Costello led a faecal microbiota transplantation (FMT) study the results of which demonstrate the ability to induce remission in UC, without significant side-effects. [src]