In a correspondence today a reader wrote:

Conditions That Release Histamine
 1. Tissue injury: Any physical or chemical agent that injures tissue, skin or mucosa are particularly sensitive to injury and will cause the immediate release of histamine from mast cells. 
2. Allergic reactions: exposure of an antigen to a previously sensitized (exposed) subject can immediately trigger allergic reactions. If sensitized by IgE antibodies attached to their surface membranes will degranulate when exposed to the appropriate antigen and release histamine, ATP and other mediators. 
3. Drugs and other foreign compounds: morphine, dextran, antimalarial drugs, dyes, antibiotic bases, alkaloids, amides, quaternary ammonium compounds, enzymes (phospholipase C). Penicillins, Tetracyclines, Basic drugs- amides, amidines, diamidines, Toxins, venoms, Proteolytic enzymes, Bradykinin, Kallidin, & Substance P  [Src]

Missing the bacteria that produce DAO and having the MAO mutation is a major part of [someone] issues.

This triggered some lateral thinking (Edward de Bono fan here). Histamine comes from mast cells. Mast cells contains TWO items:

• histamines
• heparin

What it the histamine problem was not the primary effect but the side effect?

Suppose the body is sending out a chemical message for heparin and the histamine effect is just a side effect.

Heparin is something that I am familiar with, as well as mild coagulation defects. Heparin is not a single chemical but a complex mixture of chemicals. It impacts multiple stages of coagulation.

Suppose that the natural heparin produced by the body has a defect. They do – I know from personal experience. I have the prothrombin G20210a-mutation and have been on heparin. The plead from the body for heparin provides the heparin — but it is not a complete heparin. The body keeps asking for heparin…. causing more and more histamine to be released.

The naive approach to test this hypothesis would be to take heparin!

Any Evidence?

The involvement of coagulation factors, such as tissue factor and fibrinogen, in the pathogenesis of asthma has been reported. The finding of platelet activation in asthma also indicates a link between bronchial inflammation and hemostasis. The pathogenesis of mast celldegranulation and CSU was also shown to be associated with the activation of hemostatic factors such as fibrinogen and FXIIa.

Hemostasis in Allergy. [2018]

Chronic spontaneous urticaria (CSU) [HIVES] is a common skin disorder characterized by daily or almost daily recurring skin edema and flare with itch. Recently, the activation of the blood coagulation cascade has been suggested to be involved in CSU, but the trigger of the coagulation cascade remains unclear.

Chronic spontaneous urticaria and the extrinsic coagulation system. [2018]

Mast cell heparin released upon activation provides negatively charged surfaces for factor XII (FXII) binding and auto-activation. Activated FXII, the initiating serine protease in both the contact and the intrinsic coagulation system, activates factor XI and prekallikrein, respectively. FXII-mediated bradykinin (BK) formation has been proven in the human plasma of anaphylactic patients as well as in experimental models of anaphylaxis.

The Mast Cell, Contact, and Coagulation System Connection in Anaphylaxis. [2017]

Has it been tried?

• ” The inhibitory action of medium molecular weight heparinyl phenylalanine (MHF) on the type I allergic reaction was due to a reduction or delay in histamine release from mast cells. MHF may be a potent anti-allergic agent. ” [2019]
• ” Chondroitin sulfate and Heparin may inhibit secretion of histamine from rat connective tissue MC, but their effect on human MC remains unknown.  ” [2018]

Bottom Line

This is just a hypothesis. I could not find any paper on testing for inherited coagulation defects of patients with histamine issues. The hypothesis is a feedback loop caused by ‘corrupt heparin’ being produced and the body asking for complete heparin. The over production of histamine is a side effect of this loop.

While working on an email response to a reader’s question about mold/mycotoxins, I found this 2018 article: Mycotoxin: Its Impact on Gut Health and Microbiota.

Evidence of disturbance on gut microbiota modulation induced by mycotoxin only had been studied on animal and the results have been summarized (Table ​(Table1).1). The changes in gut microbiota can be observed up to species level in some of the studies using advance molecular approaches. However, the compositions of gut microbiota are greatly influenced by various factors during the experiment. Confounding factors affecting microbial composition and function may include diet (Cani and Everard, 2016), the exposure of environmental chemical and antibiotics (Claus et al., 2017), genetic background (Goodrich et al., 2016b), as well as the mental health condition (stress) of the host (Karl et al., 2017). These factors can explain that the microbiota in same species may not be able to reduce the level of mycotoxins. Besides, the changes in gut microbiota due to the presence of mycotoxin may contribute by some uncontrolled variables. 

Mycotoxin: Its Impact on Gut Health and Microbiota.

The highlighted text above is echo in natural observations. For example avocado cannot be handle by some bird species, chocolate and xylitol to dogs [src]. I suspect the same for humans — depending on the microbiome / DNA, sensitivity to mold is high in some and safely decomposed in others.

This may be due to explicit strains or epigenetic side-effects:

Interestingly, a study showed the ability to metabolize DON can be obtained via gut microbiota transfer in swine. However, the transfer of gut microbiota revealed no changes in the DNA-profiles of the gut bacterial composition (Eriksen et al., 2002).

Bacteria Able to Transform some toxins

From the above article, we have:

• Anaerofilum, Bacillus Clostridiales, and Collinsella (Yu H. et al., 2010).
• a significant increase of Bacteroides/Prevotella group and decreased concentration levels of Escherichia coli were observed after feeding the rats  with Deoxynivalenol  (DON)
• The first study on the effect of Zearalenone (ZEA) on gut microbiota has been carried out by Piotrowska et al. (2014). …  the data showed the concentration of Clostridium perfringens, Enterobacteriaceae, and E. coli was significantly reduced 
• showed that Lactobacillus reuteri present during the start-up period, was permanently disappeared at the end of the Ochratoxin A treatment period accompanied by some minor changes in the bifidobacteria population… the relative abundance of Lactobacillaceae was increased whereas the Bacteroidaceae was decreased. 
• The exposure of gilts to ZEA and DON was found to pose an adverse impact on mesophilic aerobic bacteria. In particular, the amounts of C. perfringens, E. coli, and other bacteria in the family Enterobacteriaceae were reduced significantly after the 6th week of the experiment (P < 0.05)… , a study confirmed AF and fumonisin mixture increased Shiga Toxin-producing E. coli (STEC) level in fecal   

Probiotics

Prohep [Lactobacillus rhamnosus GG, heat-inactivated VSL#3, and viable E. coli Nissle 1917 (1:1:1)] successfully relieved the microbial imbalance and hepatic inflammation, which further decreased liver tumor growth (Li et al., 2016).  A human study by El-Nezami et al. (2006) demonstrated a statistically significant decrease (up to 55% at 5th week; P < 0.05) of urinary AFB-N7-guanine level in the probiotic (L. rhamnosus LC705 and Propionibacterium freudenreichii subsp. shermanii) mixture group compared to the placebo group. Similar finding was found by Mohd Redzwan et al. (2016) where serum AFB1-lys level were significantly lower (P < 0·05) in the Lactobacillus casei Shirota supplemented individuals. Besides, hepatic transcriptome in AFB1-induced HCC was positively altered by probiotics (Monson et al., 2015).

Bottom Line

From the above excellent review, I would infer the following treatment options:

• For mold exposure, a FMT from a person subject to the same mold exposure that did not react. Why: They likely have bacteria that is able to decompose the toxins. The logic is akin to using serum from a survivor of an infection.
• The following probiotics (I have ranked order them by my personal preference)
  1. Mutaflor – E.Coli Nissle 1917: Why: This is a robust probiotic that inhibits Shiga Toxin-producing E. coli (STEC)
  2. Lactobacillus casei Shirota (see this post on Yakult)
  3. Propionibacterium freudenreichii  (see this post)
  4. Lactobacillus rhamnosus GG (see this post “A MCS Probiotic?“)

The full text of the article is here, with links to earlier studies in the margin.

Quick review of the numbers for my various components.

Blog continues to grow in Readership

Facebook Page over last 28 days

Microbiome Site

Bottom Line

77K (21%) to http://microbiomeprescription.com/

282K (79%) to this Blog site

A reader asked me about this probiotic. It is unusual because it contains some species not seen in other probiotics.

Review of the atypical species

This looks like an impressive list of atypical species.

• Lactococcus Cremoris – “It is not a natural inhabitant of the human gastrointestinal tract, but does survive passage through it, and has been used to deliver bioactive peptides to the gut. ” [src]
• Lactobacillus Kefir – Wikipedia – used in making kefir
• Lactobacillus parakefiri – Wikipedia – used in making kefir
• Lactobacillus lactis biovar diacetylactis – starter for cheese [src]
• Associated with Sausage Making
  • Leuconostoc lactis – Wikipedia –
  • Leuconostoc mesenteroides – Wikipedia –
  • Leuconostoc cremoris – Wikipedia –
  • Leuconostoc dextranicum – Wikipedia –
• Following are YEASTS
  • Kluyveromyces marxanus – Wikipedia – has been associated with candidemia
  • Brettanomyces anomalus – Wikipedia – Brewing – no human impact information could be located.
  • Debaryomyces hansenii – Wikipedia – no human impact information could be located.
  • Saccharomyces unisporus – nill
  • Saccharomyces turicensis – nil
  • Saccharomyces cerevisiae – Wikipedia – Bread, Brewing – no human impact information could be located.
  • Saccharomyces exiguus – Wikipedia– Bread – no human impact information could be located.
  • Torulaspora delbrueckii – Wikipedia – Wine – no human impact information could be located.

Ding — Tossing the kitchen sink in to make a product

My impression after finding that most of these are used in brewing, wine making, sausage making — etc. Is that someone decided to toss a stack of commercial products used in food production to make a nice sounding product.

My challenge to the manufacturer (or their representatives) is to provide pubmed citations for each and every species cited above showing they have medical benefit. It they are unable, then the hypothesis that this is not a health-orientated engineered product but a marketing-to-the-masses marketing product, appears probable.

A year end review of recent literature and findings on pubmed. Oral Fecal Matter Transplants have been practised by canines forever (as every dog owner knows), evidence suggests (once various safety and regulatory issues are resolved) that it may be far superior to probiotics.

The advent of these applications for MTs poses challenges for regulatory bodies. The transplanted material is not a “typical” drug, and thus may not be appropriate for the drug regulatory pathway. The material consists of a community of highly dynamic, metabolically active organisms (9). Many of the transferred organisms are challenging to culture in vitro, and it is difficult to test their effectiveness in animals (9). Each batch of “product” is different, making characterization of the transplanted material problematic.

Improving regulation of microbiota transplants.

In this first article, the shift in the type of bile acid in significant.

A consistent metabolic signature was identified in the post-transplant microbiota, with reduced primary bile acids and substantial restoration of secondary bile acid production capacity. Total Fatty Acid (FA) levels were unchanged but the ratio of inflammatory to non-inflammatory FAs decreased.

Changes in microbiota composition, bile and fatty acid metabolism, in successful faecal microbiota transplantation for Clostridioides difficile infectio

Implication to how donor diets should be modified.

we show that obese mice receiving FMTs from healthy resveratrol-fed mice have improved glucose homeostasis within 11 days of the first transplant, and that resveratrol-FMTs is more efficacious than oral supplementation of resveratrol for the same duration. 

Fecal transplant from resveratrol-fed donors improves glycaemia and cardiovascular features of the metabolic syndrome in mic

• Fecal microbiota transplantation against intestinal colonization by extended spectrum beta-lactamase producing Enterobacteriaceae: a proof of principle study.
• Faecal microbiota transplant: a novel biological approach to extensively drug-resistant organism-related non-relapse mortality.

Two cancer patients were successfully treated with fecal microbiota transplants (FMTs) for colitis caused by immunotherapy, according to a case report published today (November 12) in Nature Medicine. Both patients accepted donors’ gut microbiomes following the procedure and their symptoms cleared up within weeks.

A case study of two patients with advanced cancer shows it might be possible to avoid a common and severe side effect of immunotherapy treatment.

Previous work has suggested that people whose transplanted organs get rejected tend to have certain bacteria in their gut. But though bacteria causing the rejection is one explanation, so is the reverse – that rejection encourages growth of the bacteria.

Faecal swaps could help stop heart transplants from being rejected

A single treatment using an optimized, targeted form of faecal microbiota transplantation (FMT) produces sustained clinical and cognitive improvements, according to the results of a long-term follow-up of patients with liver cirrhosis and hepatic encephalopathy (HE) who had participated in a short-term study. 

Fecal microbiota transplantation produces sustained improvements in cognitive and clinical outcomes

IBS

Fecal microbiota transplantation improved symptoms in patients with refractory irritable bowel syndrome with severe abdominal bloating, according to research presented here.

Fecal transplant improves refractory IBS with abdominal bloating

Fecal microbiota transplantation altered the gut microbiota of patients with irritable bowel syndrome, but it was not superior to placebo for improving symptoms in a study presented at Digestive Disease Week.

Fecal transplant alters gut microbiome in IBS patients

In the study of 18 children with autism and moderate to severe gastrointestinal problems, parents and doctors said they saw positive changes that lasted at least eight weeks after the treatment. Children without autism were included for comparison of bacterial and viral gut composition prior to the study.

Autism symptoms improve after fecal transplant, small study finds

On DYI FMT

• When an FDA Ruling Curbed Fecal Transplants, I Performed My Own.
• DIY faecal transplants carry risks including HIV and hepatitis, warn experts
• The Rise of the Do-It-Yourself Fecal Transplant
• Fecal Transplant Pills Could Become a New Cutting-Edge Treatment for Infections
• In the US, a nonprofit stool bank is operating. OpenBiome

Full Disclosure: I have talked to people who have done DYI oral FTMT (DYIOFMT ???) with positive results. These individuals were very intelligent, aware of risks and issues, and do near-professional due-diligence.