A reader wrote with an interesting question:

I want to create 2 probiotic formulas for myself but need help in determining approximate percentages of each of these strains.
% of: B-Bifidum, B-Breve, L-Salivarious etc

The question is how to answer this!

Ways of Determining Ratios

Looking at this question, I see several logical roots:

• A proprietary blend (keep secret on the ratio – more below)
• The percentage seen in appropriate human samples (usually healthy controls)
• Result of experiments with different ratios and picking the ratio with the best results.

I will deal with the first and last approach first, and then go on to the middle one.

A proprietary blend

Unfortunately, there are no published studies in this area – proprietary means not public. Existing formulation on the market appear to be based on proprietary processes. In better cases it is likely to get past a min level (i.e. reported in some study) for each individual probiotic and then ‘pad’ with the cheaper ones until they hit a BCFU that was determined by marketing studies. In the worst case, it is determined by a marketing study of competitors.

Base on Human Studies with different mixtures

I have never seen such a study done. I recall a very few where there are three groups: {Control, Mixture of A and B, just A}. This does not answer the percentage question at all.

This is further complicated because of some studies reporting no results for a probiotic and another study reporting positive results. Doing a proper valid study is both very time consuming and very expensive.

Based on observed ratios in Human Samples

This is the simplest to do. It has two challenges:

• Defining the target population
• Insuring that the testing (usually 16S) methodology measures all of the candidate strains.

I do have a contributed set of human samples and let us see what the results are assuming this is the target population.

Proposed Bifidobacterium Ratios

The numbers below are the result of a little data manipulation (any one proficient in R can repro these numbers

Looking at the common species likely to be available for probiotics

Proposed Lactobacillus Ratios

The numbers produced are very interesting – Lactobacillus acidophilus is far very down the list!

Looking at the common strains, we see a very interesting set of ratios:

Some 114 taxonomy units of Lactobacillus are currently in the sample

Bottom Line

Well, I did create one possible answer to the question that the user asked. A firm like Thryve or Ubiome can likely produce more definitive data. If either firm care to share their numbers with me — I would be glad to share they results here.

Firms like CustomProbiotics or Seed may wish to produce mixtures matching the above ratios (or obtained in the same way elsewhere). Lactobacillus and Bifidobacterium appear to be close to a 1:1 ratio.

What I found especially interesting is that there appear to be some species that IMHO should be more available as probiotics — but are not. Especially the following:

• Lactobacillus ruminis
• Lactobacillus iners
• Lactobacillus crispatus
• Lactobacillus jensenii

A reader asked me review the treatment options and risk. DED is often associated with Sjogren’s syndrome which is frequent with
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)  [1999]

• “Asian ethnicity is a mostly consistent dry eye disease (DED) risk factor.” [2019] 
• The prevalence of DED is high, with global estimates ranging from 5 to 50% of the adult population [4], and the economic burden from the disease is expected to riseas populations age [5]. 

Sjogren’s syndrome has distinctive microbiome shifts [2019] [2018] [2017]. A 2018 study on mice found that DED reversed with a fecal transplant.

The administration of probiotics strains was effective in reducing DES. In light of these results, we have identified our probiotic (Saccharomyces boulardii MUCL 53837 and Enterococcus faecium LMG S-28935) activity integration with the action of tear substitutes, along with standardization of clinical parameters of the tear film and microbiological activity in restoring of the microbiota ocular surface subject with DES.

Aging Eye Microbiota in Dry Eye Syndrome in Patients Treated with Enterococcus faecium and Saccharomyces boulardii. [2017]

 a combined dietary supplement containing fish oil, lactoferrin, zinc, vitamin C, lutein, vitamin E, γ-aminobutanoic acid, and Enterococcus faecium WB2000 on dry eye. .. Supplementation improved objective and subjective dry eye symptoms.

Dietary Supplementation with a Combination of Lactoferrin, Fish Oil, and Enterococcus faecium WB2000 for Treating Dry Eye: A Rat Model and Human Clinical Study. [2016]

• “A moderate daily dose of both forms of long-chain ω-3 EFAs, for 3 months, resulted in reduced tear osmolarity and increased tear stability in people with DED.” [2017]  [2017] [2015]

Prescription Interventions

“Twenty-six unique trials investigating 13 ophthalmic drugs were identified, including trials of the approved drugs cyclosporine A, cyclosporine A cationic emulsion, diquafosol, rebamipide and lifitegrast. ….
 Publications on lifitegrast reported statistical superiority in a symptom or sign endpoint versus the control group in a large (N > 200), multicenter trial, with results repeated in trials of similar design.  ” [2019 – long full text article]

• Xiidra (lifitegrast ophthalmic solution) 5% is a lymphocyte function-associated antigen-1 (LFA-1) antagonist indicated for the treatment of the signs and symptoms of dry eye disease (DED).
  • “The most common adverse reactions reported in 5-25 % of patients were instillation site irritation, dysgeusia and reduced visual acuity.” [FDA]
  • “In vitro studies demonstrated that lifitegrast may inhibit T-cell adhesion to ICAM-1 in a human T-cell line and may inhibit secretion of inflammatory cytokines in human peripheral blood mononuclear cells. The exact mechanism of action of lifitegrast in dry eye disease is not known. ” 
  • “Self-reported adverse reactions were noted in 31.4% of patients.” [2019] 

Bottom Line

My preference is usually non-prescription approaches — especially an avoidance of new drugs where long term consequences are still to be determined. Xiidra was approved in 2016, so it is just 3 years on the market. Some of the reaction listed on WebMed.com suggests that people with histamine or mast cells issues may have issues.

Enterococcus faecium probiotics and omega-3/fish oil combination appears to be demonstrated to help. I know of two (only) Enterococcus faecium probiotics:

• Symbioflor-1 (Available from the German Apotheke in the US)
• Bioflorin ( Enterococcus faecium SF68 or E. faecium NCIMB 1041 or Streptococcus faecium SF68)

We also have

• Biofermin S Tablet (from Japan) a mixture, on Amazon
  • Bifidobacterium Bifidum
  • Enterococcus Faecalis
  • Lactobacillus Acidophilus
    

There were no probiotic studies for Sjogren’s syndrome that I could locate. There was some work to engineer a probiotic (A Novel Probiotic for the Treatment of Sjogren’s Syndrome).

A good friend for almost two decades also writes a blog Cort Johnson (HealthRising) and is attending the National Institute of Health ME/CFS conference and giving regular reports on his notes (the above link goes to one of them). Several of them caught my eye — today, I will look at the report of high uranium levels being detected in ME/CFS patients.

Early hair analysis results highlight increased mercury and uranium (!) levels associated with decreased selenium levels. The sample size is small, however….
Then came a preliminary but really weird finding – elevated levels of mercury (not so weird) and high levels of uranium (really weird) associated with low selenium levels in the hair analyses of a significant subset of patients. Both the mercury and uranium issues derive from low selenium levels. Selenium, interestingly, also plays a role in the conversion of T4 to T3 in the thyroid. (Chris Kressler recommends getting your selenium levels tested and, in general, using
 dietary methods (not selenium supplementation) to safely 
increase selenium levels in hypothyroidism.)

The NIH ME/CFS Conference II: Lipkin’s Possibilities, Prusty’s Big Idea, Oh’s Search and Ron Davis on ALWAYS Moving Forward, Apr 15, 2019

I have selenium as one of my core recommendations – which the above reinforces. The reasons that I cite on earlier posts (see prior link for more studies)

• 78% of IBS patients examined showed selenium insufficiency [2007],
• Low selenium is associated with hypothyroidism [2015]
• FM has lower selenium levels [1998]
• Selenium supplement improved the condition of CFS rats [2018]

Uranium and mercury is frequently found in trace amount in drinking water [2018], as well as in human placenta [2016] and US children [2010]. It appears, for reasons not currently understood, that the body retains more of those two minerals when it is short of selenium. (“Significant pairwise correlations were observed for a number of metals.” [2010]) Some additional interesting studies:

• “Our results suggested that asthma prevalence in the Chinese adults was positively associated with urinary chromium, chromium, selenium, molybdenum, cadmium, and uranium, ” [2016]
• Impacts of selenium supplementation on soil mercury speciation, and inorganic mercury and methylmercury uptake in rice (Oryza sativa L.).[2019] “As a result, inorganic Hg (mercury) was reduced by >48%, 18%, and 80% in root, stem, and grain “
  • Immobilization of elemental mercury by biogenic Se nanoparticles in soils of varying salinity.[2019]
• Selenium, total mercury and methylmercury in sardine: Study of molar ratio and protective effect on the diet. [2019]
• “the selenium content in canned sardine samples is enough to provide a protective effect on the Hg species. “

Bottom Line

Preferred sources are from food (a list here) but not that malabsorption does occur with gastrointestinal condition (i.e. microbiome dysfunction).

Selenium Toxicity does occur with supplements — so the safest course is to get measured and under medical supervision for supplementation.

The source of the outbreak was identified as a liquid dietary supplement that contained 200 times the labeled concentration of selenium. Of 201 cases identified in 10 states, 1 person was hospitalized. The median estimated dose of selenium consumed was 41 749 μg/d (recommended dietary allowance is 55 μg/d). Frequently reported symptoms included diarrhea (78%), fatigue (75%), hair loss (72%), joint pain (70%), nail discoloration or brittleness (61%), and nausea (58%). Symptoms persisting 90 days or longer included fingernail discoloration and loss (52%), fatigue (35%), and hair loss (29%). The mean initial serum selenium concentration of 8 patients was 751 μg/L (reference range, ≤125 μg/L). The mean initial urine selenium concentration of 7 patients was 166 μg/24 h (reference range, ≤55 μg/24 h).

Acute Selenium Toxicity Associated With a Dietary Supplement 2010

A reader who has several family members with conditions that have microbiome shifts associated asked about cardiac disease, which is frequent in one side of the family.

Below is what I could find. This is a new area of research that I expect to explode in the next few years.

” Dysbiosis of the intestinal flora has been associated with insulin resistance, diabetes mellitus and cardiovascular diseases, such as atherosclerosis and heart failure. ” [2019]

” In the recent years, both human and animal experiments have revealed that alterations in the composition and function of intestinal flora, recognized as gut microflora dysbiosis, can accelerate the progression of cardiovascular diseases. “[2019]

The gut microbiomes of VC and CAD patients were significantly different in terms of beta-diversity. Bacteria from Veillonella dispar, Bacteroides plebeius and Fusobacterium were enriched in the VC group, while members of Collinsella aerofaciens, Megamonas, Enterococcus, Megasphaera, Dorea and Blautia were decreased. According to the association with dyslipidemia, seven operational taxonomic units (OTUs), including Parabacteroides distasonis, Megamonas, Fusobacterium, Bacteroides sp., Bacteroides plebeius, Lactobacillus and Prevotella copri, were regarded as potential pathogens for CVDs. Additionally, Prevotella copri might be a keystone of CVDs, especially in VC patients, while Collinsella aerofaciens is a possible keystone of CAD, based on the multi-correlations of these bacteria with other OTUs in microbial communities.

The intestinal microbiota associated with cardiac valve calcification differs from that of coronary artery disease[2018].

• Suppression of the gut microbiome ameliorates age-related arterial dysfunction and oxidative stress in mice.[2019]
• Higher Fecal Short-Chain Fatty Acid Levels Are Associated with Gut Microbiome Dysbiosis, Obesity, Hypertension and Cardiometabolic Disease Risk Factors. [2018]
• Loss of Gut Microbiota Alters Immune System Composition and Cripples Postinfarction CardiacRepair. [2019]
• The gut microbiome and heart failure. [2019]
• Interaction between gut microbiome and cardiovascular disease. [2018]
• Design of the GutHeart-targeting gut microbiota to treat heart failure-trial: a Phase II, randomized clinical trial. [2018]

Bottom Line

You will note that almost all of the studies cited above were done this year and last year. This is an area that is actively being researched because the evidence indicate strongly that there is a relationship.

Because cardiac disease has many divisions and the amount published on each is sparse, I will not include this on my analysis site yet.

Some early feedback has resulted in my adding a new page. This is providing more detail on this earlier post. On the Analysis page (where you are sent once a sample is selected), you will see a new link, shown below:

Clicking on this will take you to a page showing the 10 most atypical bacteria (all levels), as shown below. Three examples — all for the same person over 3 years. With the new algorithm, too low is rarely seen.

Clicking on the name will take you to the reference library so you can see the known information about each. This allows you to custom build your suggestions (instead of automatic suggestions).