This is the start of a new year and new decade. I am a data consolidator not a physician or medical person. I am an Expedia or Travelocity not a KLM, Delta or Air India. If the information on this site or http://microbiomeprescription.com/ has had a positive effect on you, consider adding your experience as a comment. Be specific and try giving the following information:

• What data did you base that decision on? (Thryve, uBiome, GI Map)
  • The specific condition/symptom that you were attempting to address
• What did you try (including brand and web link)
  • If this came from a specific post or page, include it
• When was the positive outcome or change (i.e. how long to see changes)

The purpose is to give encouragement and hope to others struggling with issues.

Thanks — and have a good new year on this 8th day of Twelveth Night!

However, Bifidobacteriaceae are capable of binding iron in the large intestine, thereby limiting the formation of free radicals synthesized in the presence of iron, and thus reducing the risk of colorectal cancer. Animal studies have revealed that supplementation with probiotics, prebiotics and synbiotics has a significant effect on bone calcium, phosphate and bone metabolism. The dynamic interaction between microbiota and zinc was shown. Human studies have provided evidence of the influence of probiotic bacteria on parathormone, calcium and phosphate levels and thus on bone resorption. Recent studies have produced new information mainly on the impact of the intestinal bacteria on the metabolism of calcium and iron. From a scientific perspective, the most urgent fields that remain to be investigated are the identification of all human gut microbes and new therapies targeting the interaction between intestinal bacteria and minerals.

Association between the gut microbiota and mineral metabolism. [2018]

In this post, I will try finding the studies and further information.

• A Systematic Review and Meta-Analysis on the Effects of Probiotic Species on Iron Absorption and Iron Status.[2019] “Lactobacillusplantarum 299v  significantly improved iron absorption in humans. ” i.e. Jarrow Formulas Ideal Bowel Support 299v
• Enhancement in Iron Absorption on Intake of Chemometrically Optimized Ratio of Probiotic Strain Lactobacillus plantarum 299v with Iron Supplement Pearl Millet. [2019]
• Identification of the key excreted molecule by Lactobacillus fermentum related to host iron absorption. [2017] – Increases iron
• Probiotic strain Lactobacillus plantarum 299v increases iron absorption from an iron-supplemented fruit drink: a double-isotope cross-over single-blind study in women of reproductive age. [2015]
• Fecal total iron concentration is inversely associated with fecal Lactobacillus in preschool children. [2017] — so specific lactobacillus species may determine increase or decrease of Iron
• Probiotics Lactobacillus reuteri DSM 17938 and Lactobacillus casei CRL 431 modestly increase growth, but not iron and zinc status, among Indonesian children aged 1-6 years. [2013]
• Effects of a Multispecies Probiotic Supplement on Bone Health in Osteopenic Postmenopausal Women: A Randomized, Double-blind, Controlled Trial. 2017 Increase of calcium from probiotic containing: Lactobacillus rhamnosus, Lactobacillus bulgaricus, Lactobacillus casei, Lactobacillus acidophilus, Bifidobacterium breve , Bifidobacterium longum, Streptococcus thermophilus

• The Effect of Multispecies Probiotic Supplementation on Iron Status in Rats.[2019] Serum Fe was lower in probiotic groups
• Effect of probiotics on the basis of Bacillus subtilis and Bifidobacterium longum on the biochemical parameters of the animal organism.[2018] ”  At the end of the experiment, the content of calcium in the body tissues of animals of group (Bifidobacterium longum)  exceeded this indicator in group (Bacillus subtilis 534) by 3.9%, phosphorus by 17.6%, copper by 28.5%, and zinc by 15.2%.  “
• Probiotics Lactobacillus reuteri DSM 17938 and Lactobacillus casei CRL 431 modestly increase growth, but not iron and zinc status, among Indonesian children aged 1-6 years. [2013]
• The probiotic bacterial strain Lactobacillus fermentum D3 increases in vitro the bioavailability of Ca, P, and Zn in fermented goat milk.[2013]
• Influence of Bifidobacterium bifidum on release of minerals from bread with differing bran content. [2012] ” Bifidobacterium bifidum KD6 enhanced amounts of magnesium and zinc released from all types of bread, while manganese and copper rose only from white bread with 15% bran addition. Bacteria decreased amounts of calcium and iron released from bread. “
• Bifidobacterium dentium Fortifies the Intestinal Mucus Layer via Autophagy and Calcium Signaling Pathways. [2019] ” We also identified that B. dentium-secreted products, such as γ-aminobutyric acid (GABA), stimulated autophagy-mediated calcium signaling and MUC2 release “
• ” that arsenic and mercury were significantly associated with Parabacteroides and Oscillospira in the gut. ” [2019]

Bottom Line

The available literature suggests that Lactobacillus and Bifidobacterium are dominate player for calcium levels. Since these are much higher in children than adults, this would assist in bone growth by providing the needed calcium. This appears to extend to other minerals such as zinc, copper, phosphorus in a similar manner.

Both Lactobacillus and Bifidobacterium decrease with old age and may account for calcium /bone loss issues. ” The presence of the Bifidobacterium, Faecalibacterium, Bacteroides group, and Clostridium cluster XIVa decreased with age up to 66-80 years of age,  “[2019]

Low levels of one of more of theses would hint towards insufficient of these, or a bad balance with them. High levels of one or more would hint towards a surplus of these, or a bad balance with them.

A reader with ME/CFS wrote:

One of the many tests over the years has been Natural Killer cell function. Many CFS patients from what I understand have low NK cell function.
 Any clue how this is related to microbiome and ways to possibly reverse this or restore NK function? Could this just be due to gut dysregulation?

This has been my assumption for over 6 years. The following is what I could find that has been documented:

• “Some effects of modulation by probiotics include cytokine production by epithelial cells, increased mucin secretion, increased activity of phagocytosis, and activation of T and natural killer T cells, stimulation of immunoglobulin A production and decreased T cell proliferation. Intestinal microbiota has a major impact on the systemic immune system. ” [2019]
• ”  Some probiotics have been found to regulate immune responses via immune regulatory mechanisms. T regulatory (Treg) cells, T helper cell balances, dendritic cells, macrophages, B cells, and natural killer (NK) cells can be considered as the most determinant dysregulated mediators in immunomodulatory status.  ” [2019]

The gut microbiota is a key element to support host homeostasis and the development of the immune system. The relationship between the microbiota and immunity is a 2-way road, in which the microbiota contributes to the development/function of immune cells and immunity can affect the composition of microbes…. Our results indicate that intestinal NKT cells are important modulators of intestinal homeostasis and that gut microbiota composition may be a potential target in the management of inflammatory bowel diseases.  

Fecal IgA Levels and Gut Microbiota Composition Are Regulated by Invariant Natural Killer T Cells. [2019]

The review compiles data from multiple studies on the role of microbiota in the innate immune response and the development and differentiation of CD4⁺ T cells, a major component of the adaptive arm of the immune response. As a result of dysbiosis, invariant natural killer T cells may induce T helper 2 cell differentiation and immunoglobulin E isotype switching through the release of Interleukin-4 and Interleukin-13. Furthermore, degradation of immunoglobulin A antibodies, increased circulating mast cells and basophils, and inflammation are among other mechanisms by which dysbiosis can induce or exacerbate asthma. 

The Role of Gut Microbiota in Atopic Asthma and Allergy, Implications in the Understanding of Disease Pathogenesis. [2019]

Some bacterial species (e.g. Prevotella, Citrobacter rodentium, Collinsella aerofaciens, Segmented filamentous bacteria) participate in the creation of the pro-inflammatory immune status, presumably via epitope mimicry, modification of self-antigens, enhanced cell apoptosis mechanisms, and destruction of tight junction proteins and intestinal barrier integrity, all leading to the development and maintainance of inflammatory arthropathies… The underlying mechanisms include dysbiosis-mediated changes in the functional activity of the intestinal immune cell subsets, such as innate lymphoid cells, mucosa-associated invariant T cells, invariant natural killer T cells, T-follicular helper and T-regulatory cells. In turn, disturbed functionality of the gut-associated immune system is shown to promote the overgrowth of many bacteria, thus establishing a detrimental vicious circle of actively maintaining arthritis.

A cross talk between dysbiosis and gut-associated immune system governs the development of inflammatory arthropathies. [2019]

Recent evidence indicates that memory is also present in the innate immune cells such as monocytes/macrophages and natural killer cells. These cells exhibit pattern recognition receptors (PRRs) that recognize microbe- or pathogen-associated molecular patterns (MAMPs or PAMPs) expressed by the microbes. Interaction between PRRs and MAMPs is quite crucial since it triggers the sequence of signaling events and epigenetic rewiring that not only play a cardinal role in modulating the activation and function of the innate cells but also impart a sense of memory response. 

Potential Role of Gut Microbiota in Induction and Regulation of Innate Immune Memory. [2019]

• Intestinal microbes affect phenotypes and functions of invariant natural killer T cells in mice. [2012]
• Supplementation with galacto-oligosaccharides increases the percentage of NK cells and reduces colitis severity in Smad3-deficient mice. [2012]
• Bacteria associated with immunoregulatory cells in mice. [2010]
• Control of intestinal homeostasis through crosstalk between natural killer T cells and the intestinal microbiota. [2015]

Bottom Line

I stopped following studies on natural killer cells a few years ago because the evidence pointed to them being a secondary effect of issues with the microbiome. In other words, a symptom and not a cause. Symptom relief is good but it does not deal with the root cause. Altering natural killer function by drugs do have a chance of causing a cascade into the microbiome ( it is a 2-way road ), unfortunately drugs also have unknown side effects. I have focused on the microbiome because it is easier to do in one sense (no need to talk a MD into prescribing, no fight with insurance company to pay for it), it is also more complex to do — which is why I ended up writing a fuzzy logic artificial intelligence system to do it.
http://microbiomeprescription.com/

A reader asked me about doing this. I have no personal experience (I am sure some readers will add their own experiences to this post). I did find a few items on Pub Med

 The preliminary clinical trials and animal experiments show that the probiotics biologicals from Lactobacillus acidophilus or Bifidobacterium, and the prebiotics including inulin and galactooligosaccharides, as well as lubiprostone and activated carbon adsorbents can be used for improving dysfunction of CKD patients with the gut microbiota dysbiosis via reducing uremic toxins and inhibiting the systemic micro-inflammation. But not only that, it is reported that, to some extent, a number of the single Chinese herbal medicine（CHM）, the CHM prescriptions and the CHM extracts（emodin, etc.）with oral or enema administration can also regulate the gut microbiota dysbiosis, protect the intestinal epithelial barrier, reduce uremic toxins accumulation and delay CKD progression.

[Pathomechanism and treatment of gut microbiota dysbiosis in chronic kidney disease and interventional effects of Chinese herbal medicine]. 2017

• Randomised clinical trial: the effectiveness of Lactobacillus reuteri ATCC 55730 rectal enema in children with active distal ulcerative colitis.[2012] ” In children with active distal ulcerative colitis, rectal infusion of L. reuteri is effective in improving mucosal inflammation and changing mucosal expression levels of some cytokines involved in the mechanisms of inflammatory bowel disease. “
• Effects of budesonide and probiotics enemas on the systemic inflammatory response of rats with experimental colitis. [2007] ” Probiotics are effective to diminished inflammatory status mediated by IL-6 in experimental colitis. “
• Clinical trial: probiotic treatment of acute distal ulcerative colitis with rectally administered Escherichia coli Nissle 1917 (EcN) [2010] ” Enemas with 40 ml EcN seem to be most promising. “

Bottom Line

No adverse reactions were cited. Results were either positive or none. It presents an interesting alternative for some people.

A reader asked not for probiotics that do not produces histamine (the usual ask), but ones that reduces histamine and mask cell issues. The following is what I could find in the literature. Mast cell issues are increasingly implicated with digestive issues. Release of histamine from mast cells cause inflammation.

” a growing body of publications clearly showed that patients with postinfectious IBS have increased Mast Cell [MC] activation… it has been recently demonstrated that dietary administration of S. cerevisiae‐derived β‐glucan was able to attenuate MC‐induced intestinal hyperpermeability in patients affected by Crohn’s disease ileitis as well as in noninflammatory IBD subjects,”

Mast cells at the crossroads of microbiota and IBD. [2018]

This article Mast cells at the crossroads of microbiota and IBD. [2018], lists some specific impacts. “several commensal bacteria such as Enterococcus fecalis, Lactobacillus paracaseii, and nonpathogenic Escherichia coli are able to suppress murine MC degranulation  “

• Enterococcus faecalis – Suppression of IgE/Ag‐induced degranulation, Reduction of MC infiltration and serum IgE levels in a murine model of atopic dermatitis
• Lactobacillus paracasei – Suppression of IgE/Ag‐induced degranulation
• Escherichia coli – Suppression of IgE/Ag‐ and PMA/ionomycin‐induced degranulation
• Saccharomyces cerevisiae – Attenuation of MC‐induced intestinal hyperpermeability

Oral administration of Clostridium butyricum CGMCC0313-1 reduces ovalbumin-induced allergic airway inflammation in mice.[2017]

Enterococcus faecium has some evidence;

• Use of a probiotic mixture containing Bifidobacterium animalis subsp. lactis BB12 and Enterococcus faecium L3 in atopic children. [2018]

Lactobacillus rhamnosus GG has some evidence

• INVESTIGATION OF PROTECTIVE EFFECTS OF SYNBIOTICS ON ALLERGOPATHY FORMATION. [2018]
• ” Compared with placebo, Lactobacillus rhamnosus GG (LGG) and VSL#3 were associated with significantly more treatment responders ( abdominal pain severity decreased ≥1 point on a 4-point Likert scale ) ” [2015]
• Probiotic Lactobacillus rhamnosus downregulates FCER1 and HRH4 expression in human mast cells. [2011] ” Our data suggest that especially probiotic L. rhamnosus Lc705 and L. rhamnosus GG could diminish mast-cell activation and the effects of allergy-related mediators by downregulating expression of the high-affinity IgE and HRH4 receptors, and by stimulating mast-cell immune responses “

DNA Aspect

There are some mutations of DNA that can result in low levels of  DAO or diamine oxidase (what counteracts histamine). This can be a factor for histamine. See this site for how to look up in your 23andMe or Ancestry DNA.

Bottom Line

My personal recommendations, based on the literature (and ranked), are:

• Enterococcus faecalis
  • symbiopharm / symbioflor 1
  • shin biofermin (jp) /s
  • threelac contains this but also contains a known histamine producer.
• Escherichia coli
  • symbiopharm / symbioflo 2
  • mutaflor / mutaflor
• Lactobacillus paracasei
  • CustomProbiotics.com / L. Paracasei Probiotic Powder
• Lactobacillus rhamnosus GG
  • culturelle / culturelle
  • digestive care
  • spain (es) / kaleidon
  • spain (es) / ns florabiotic instant
  • spain (es) / suerobivos