Mast Cell Activation Syndrome (MCAS) has been a frustrating condition to deal with. It is likely that the microbiome is a factor but finding bacteria patterns has had poor results. Recently I did a post One Consistent Pattern Across Different Vendors Results where the agreement from different lab tests on the bacteria involved simply had not agreement (see this page to illustrate). Using estimates on compounds and enzymes using KEGG: Kyoto Encyclopedia of Genes and Genomes went two ways:
- enzymes associations was worse than bacteria
- compound produced was far better than bacteria, 31x better
I decided to drill into these associations restricted it to associations seen in ALL of uBiome, Biomesight and Ombre dataset. The goal is to do a manual walkthrough of using this data to identify issues and potential solutions.
Logic Flow
- Obtain a large collection of microbiome samples process through different labs (in our case 3)
- Estimate the net amount of compound produce from each sample
- Using the symptom annotation, determine which compound are significant using chi2
- Identify the compounds that are significant for all three labs (concurrent)
- Remove the compounds that only occur in a few labs. Assume they are probable noise
- Take a shotgun sample from an individual and compute the compounds
- Identify where we have compound matching 5 (same direction)
- Ignore/discard compound that are not produced/substrate by the bacteria in sample
- Create a list by reversing taxa->Compound to compound->Taxa that are present in sample
- Pass the bacteria list with desired shift(increase/decrease) to the Fuzzy Logic Expert System to generate suggestions
- List the suggestions
[Step 4 Above] The compounds identified are below with ALL OF THEM BEING LOW:
The numbers could be low due to either:
- Not enough being produced
- More being consumed than being produced
- Severe skewness combined with low occurance
Bacteria produces and consumes the above metabolites/compounds.
We are able to compute the impact of probiotics on the above, these are listed under Probiotics modeled on Compounds on this link. None makes it better, in fact all are predicted to make things worse. Checking PubMed (while some probiotics may help), the number of studies are surprisingly sparse. Sparse studies for something like this suggests that there may be a large number of unpublished studies showing no effect or a negative effect. These unfavorable studies are very rarely published, especially when funded by someone owning the patent of the probiotic being tested.
Trying this approach on a Shotgun Sample of someone with MCAS [Step 5]
There are 52 compounds identified above. I have a Thorne sample. 42 of the compounds were less than 1%ile, 6 were over 50%ile. The pattern was obtained using this trio of 16s-labs (ubiome, biomesight and ombre) and the pattern appears to hold true for a sample from a shotgun analysis. We have 80% agreement when randomness would suggest < 2% agreement.
Looking at the details, we see that most of the 42 had no bacteria producing these compounds. This suggests that we are dealing with sparse data and possible false identification. Restricting to those reported as > 0%ile with over 200 samples we ended up with just 11 compounds.
[Step 7 Above] Returning to our Shotgun sample above, we found the following are low.
- cis-Aconitate with 3868 producers and 3869 consumers, some found not enough. Increase producers, reduce consumers
- Oxalosuccinate with 3747 producers and 3747 consumers
- N-Acetyl-alpha-D-galactosamine 1-phosphate with 282 producers and 291 consumers, too many consumers
- (L-Cysteinyl)adenylate with 120 producers and 120 consumers
Working backwards from these 4, we end up with 3,953 taxa on our first pass. For many of these bacteria there were none reported hence the challenge of encouraging bacteria that are not there!!!
Working from what is there! [Step 9/10]
Using cis-Aconitate and N-Acetyl-alpha-D-galactosamine 1-phosphate , we want to reduce consumers and increase producers. The result is that we want to:
- Increase these bacteria (most significant is at top)
- Corynebacterium diphtheriae
- Streptococcus anginosus
- Rhodopseudomonas palustris
- Ralstonia solanacearum
- Pseudomonas oryzihabitans
- Sorangium cellulosum
- Pseudomonas putida
- Decrease these bacteria ((most significant is at bottom)
- Cupriavidus necator
- Cupriavidus basilensis
- Thermaerobacter sp. FW80
Note we are talking species here. KEGG is actually at the strain level and we extrapolated to species. Passing this data to the fuzzy logic expert system we get as suggestions [Step 11]:
- henopodium quinoa {Quinoa}
hydromorphone – an addictive pain killer- proton-pump inhibitors (prescription)
- synthetic disaccharide derivative of lactose {Lactulose}
- Moringa Oleifera {Moringa}
- Limosilactobacillus fermentum {L. fermentum}
- Heyndrickxia coagulans {B. coagulans}
- Latilactobacillus sakei {Lactobacillus sakei}
Bottom line, it is possible to get suggestions. The route is not direct. The suggestions above are typically viewed as safe (except the one crossed out), and thus I will pass it along to the person whose sample I used. At the end of multiple steps, we ended up with four (4) compounds that mapped to some 10 bacteria to shift. Those bacteria resulted in just 7 suggestions. We are travelling well outside of the mapped world.
From Perplexity AI
To increase or decrease the abundance of the listed bacteria, specific strategies should be considered, but many target species are not commonly sought for probiotic modulation due to their environmental, pathogenic, or niche-specific nature. Below, approaches to influence each are summarized when evidence is available.
Increase These Bacteria
- Corynebacterium diphtheriae: There is no safe or recommended method to purposely increase C. diphtheriae, as it is a human pathogen responsible for diphtheria, a serious disease. Laboratory studies using animal models suggest that general Actinobacteria (the phylum to which Corynebacterium belongs) can be modulated using certain yeast probiotics or lactic acid bacteria in animal models, but these findings are not intended or safe for human manipulation targeting pathogenic species. Increasing this bacterium is not medically advised.
- Streptococcus anginosus: This member of the Streptococcus anginosus group is a commensal found mainly in the mouth, throat, and gut but is also opportunistically pathogenic. There is currently no evidence-based supplement or intervention to selectively increase S. anginosus in humans; it can be affected by local tissue conditions, diet, and the existing microbiome, but any intervention to increase such bacteria outside of medical settings is not recommended.
- Rhodopseudomonas palustris: This bacterium is environmental and photosynthetic, rarely present in the human body. In agricultural or industrial settings, it is cultured using media containing carbon (like molasses), nitrogen (like corn steep liquor), and trace minerals, kept at slightly acidic to neutral pH and moderate temperatures (around 37°C). There is no role for increasing this bacteria in humans; it is used as a soil and water probiotic for plants.
- Ralstonia solanacearum, Pseudomonas oryzihabitans, Sorangium cellulosum, Pseudomonas putida: These are mainly environmental, soil, or water-dwelling microbes. There is no supplement or dietary approach to increase these in the human gut or on human mucosa, and such actions are not studied for human health.
Decrease These Bacteria
- Cupriavidus necator: This environmental bacterium can be suppressed in biotechnological fermentations by nutrient limitation (especially removing nitrogen or phosphorus), but there is no guidance for targeting this in the human body, as it is not a usual component of the human microbiome. In environmental settings, its growth is limited by removing accessible carbon, nitrogen, or phosphate sources.
- Cupriavidus basilensis: Similar to C. necator, mainly handled in environmental and fermentation settings; standard medical interventions if infection occurs would use specific antibiotics based on sensitivity.
- Thermaerobacter sp. FW80: This is a thermophilic (heat-loving) environmental bacterium not typically present in or relevant to humans. Methods to decrease it would involve lowering environmental temperatures, not relevant to dietary or supplement choices.
Practical Notes
- Most of the bacteria on your list are not normal human microbiome residents and manipulating them carries significant health risks or is not practically or ethically possible.
- For environmental and plant-associated bacteria (such as R. palustris, P. putida, Ralstonia, etc.), enrichment is done in laboratory or agricultural settings with nutrient and temperature controls but is not safe or meaningful for humans.
- For bacteria that are pathogens or opportunists (C. diphtheriae, S. anginosus), intentional enrichment is never recommended.
- For reducing rare environmental or opportunistic bacteria in humans, general good hygiene and avoiding immunosuppression help, while in clinical cases, antibiotics may be used based on sensitivity.