I’ve recently added computations for Methane and Hydrogen using KEGG data to Microbiome Prescription. Checking the contributed symptoms, I had over 120 samples with SIBO indicated. So it was time to test the hypothesis.

Charts

What about the old Methane?

The old computation was done on adhoc gathered associations from the literature. It also did not show any patterns.

Bottom Line

With the obvious path being unsuccessful, then time to examine where we did find associations.

ProductName	Pattern
(4R,5S)-4,5,6-trihydroxy-2,3-dioxohexanoate	Between 33%ile to 66%ile
cob(II)yrinate a,c diamide	Between 66%ile to 100%ile
D-tagatose	Between 0%ile to 33%ile
undecaprenyl phosphate	Between 0%ile to 33%ile

EndProduct	Pattern
Vitamin B9 (Folic Acid/Folate)	Between 66%ile to 100%ile
Lactic acid	Between 0%ile to 33%ile
2-Butanone	Between 66%ile to 100%ile
Hydrogen cyanide	Between 66%ile to 100%ile
Methyl thiocyanide	Between 66%ile to 100%ile
Propionate	Between 66%ile to 100%ile
Vitamin K	Between 66%ile to 100%ile
Vitamin B7 (biotin)	Between 66%ile to 100%ile
Sialic acid	Between 66%ile to 100%ile
Norepinephrine	Between 66%ile to 100%ile

EnzymeName	Pattern
succinyl-CoA:acetate CoA-transferase	Between 33%ile to 66%ile
phosphoenolpyruvate carboxykinase (GTP)	Between 33%ile to 66%ile

Definition	Pattern
Pentose phosphate pathway (Pentose phosphate cycle)	Between 75%ile to 100%ile
Pentose phosphate pathway, oxidative phase, glucose 6P => ribulose 5P	Between 75%ile to 100%ile
Pentose phosphate pathway, non-oxidative phase, fructose 6P => ribose 5P	Between 75%ile to 100%ile
Serine biosynthesis, glycerate-3P => serine	Between 75%ile to 100%ile
Histidine degradation, histidine => N-formiminoglutamate => glutamate	Between 75%ile to 100%ile
Riboflavin biosynthesis, plants and bacteria, GTP => riboflavin/FMN/FAD	Between 75%ile to 100%ile
Tetrahydrofolate biosynthesis, GTP => THF	Between 75%ile to 100%ile
CAM (Crassulacean acid metabolism), light	Between 75%ile to 100%ile
Lysine biosynthesis, DAP dehydrogenase pathway, aspartate => lysine	Between 75%ile to 100%ile

tax_name	tax_rank	Pattern
Blautia hansenii	species	Between 33%ile to 66%ile
Filifactor alocis	species	Between 66%ile to 100%ile
Bacteroidia	class	Between 66%ile to 100%ile
Bacteroides gallinarum	species	Between 66%ile to 100%ile

Last, we look at what studies reported

Tax Rank	Tax Name	Shift	Distribution	Citation Link
genus	Enterococcus (NCBI:1350 )	High	Distribution	📚 PubMed
genus	Klebsiella (NCBI:570 )	High	Distribution	📚 PubMed
genus	Prevotella (NCBI:838 )	High	Distribution	📚 PubMed
genus	Salmonella (NCBI:590 )	High	Distribution	📚 PubMed
genus	Staphylococcus (NCBI:1279 )	High	Distribution	📚 PubMed
genus	Streptococcus (NCBI:1301 )	High	Distribution	📚 PubMed
phylum	Firmicutes (NCBI:1239 )	Low	Distribution	📚 PubMed
species	Acinetobacter baumannii (NCBI:470 )	High	Distribution	📚 PubMed
species	Bacteroides fragilis (NCBI:573 )	High	Distribution	📚 PubMed
species	Bifidobacterium longum (NCBI:216816 )	Low	Distribution	📚 PubMed
species	Enterococcus faecalis (NCBI:1351 )	High	Distribution	📚 PubMed
species	Enterococcus faecalis (NCBI:1351 )	Low	Distribution	📚 PubMed
species	Enterococcus faecium (NCBI:1352 )	High	Distribution	📚 PubMed
species	Escherichia coli (NCBI:562 )	High	Distribution	📚 PubMed
species	Escherichia coli (NCBI:562 )	High	Distribution	📚 PubMed
species	Methanobrevibacter smithii (NCBI:2173 )	High	Distribution	📚 PubMed
species	Methanobrevibacter smithii (NCBI:2173 )	High	Distribution	📚 PubMed
species	Pseudomonas aeruginosa (NCBI:287 )	High	Distribution	📚 PubMed

Looking at the “usual suspect” for SIBO, Methanobrevibacter smithii, a methane producer, we found only 23 samples with any (and all of the labs associated with these samples reports this bacteria so over 100 (80%) of the people reporting SIBO had none appearing)

Tentatively conclusion, SIBO does not leave any clear tracks in a 16s Sample.

It is that season again — and some areas are reporting much higher levels than usual (with predictions for it getting worst). Some people will load themselves up daily on antihistamine, for example, Diphenhydramine HCl , which impacts over 800 different bacteria. We do have a profile of the bacteria shifts seen on Microbiome Prescription.

Supplements

The bad news is that we have lots of studies, but no good studies — all of them have problems…

” A total of 57 062 articles were derived from searching seven online databases and evidence from 48 RCTs and 10 observational studies were reviewed for methodological quality and risk of bias. No qualitative studies meeting the inclusion criteria could be found, therefore only a quantitative review was performed. ”

Health supplements for allergic rhinitis: A mixed-methods systematic review [2020]

• Association of Serum Vitamin D and Immunoglobulin E Levels With Severity of Allergic Rhinitis [2021] ” vitamin D deficiency is associated with increasing severity of allergic rhinitis symptoms.” [2021 ]
  • “This MR study found no evidence supporting a causal association between serum 25(OH)D levels and risk of AR, AS and NAR in European-ancestry population. ” [2021]
• Effects of vitamin E and selenium on allergic rhinitis and asthma pathophysiology [2021]
  “Our results indicated that vit E could attenuate allergic rhinitis and asthma symptoms; nevertheless, treatment with Se alone was not effective in controlling allergic symptoms. ” [2021]

Probiotics?

Lactobacillus

“Probiotics may be beneficial in improving symptoms and quality of life in patients with allergic rhinitis; however, current evidence remains limited due to study heterogeneity and variable outcome measures. Additional high-quality studies are needed to establish appropriate recommendations.”

A systematic review and meta-analysis of probiotics for the treatment of allergic rhinitis [2015]

Probiotic Potential of Lactobacillus Species in Allergic Rhinitis [2021 – full text] is a recent review with two appearing to be most likely effective (to some extent): Lactobacillus Casei and the closely related Lactobacillus Paracasei with dosages up to 30 billion CFU/day. These happen to be less than the suggested dosages from Custom Probiotic.

Bifidobacterium

If we look at Nat.Lib.of Medicine studies at Microbiome Prescription, we do not see any reports of low Lactobacillus. What we do see is low Bifidobacterium) ( Bifidobacterium longum , Bifidobacterium adolescentis, Bifidobacterium catenulatum) and Clostridium butyricum. Logically those seem better candidates!

• Probiotic NVP-1703 Alleviates Allergic Rhinitis by Inducing IL-10 Expression: A Four-week Clinical Trial[2020], a mixture of Bifidobacterium longum and Lactobacillus plantarum… ” Therefore, NVP-1703 can be treatment option for perennial AR.” [2019]
• [Allergic rhinitis management:environment control and patient education].[2017], combined clostridium and bifidobacterium capsules(called Changlekang) – good results
• Probiotics ( Lactobacillus gasseri KS-13, Bifidobacterium bifidum G9-1, and Bifidobacterium longum MM-2) improve rhinoconjunctivitis-specific quality of life in individuals with seasonal allergies: a double-blind, placebo-controlled, randomized trial [2017] “This combination probiotic improved rhinoconjunctivitis-specific quality of life during allergy season for healthy individuals with self-reported seasonal allergies; however, the associated mechanism is still unclear. “
• Bifidobacterium mixture (B longum BB536, B infantis M-63, B breve M-16V) treatment in children with seasonal allergic rhinitis and intermittent asthma [2017] “Children treated with probiotic mixture achieved a significant improvement of symptoms “

Bifidobacterium longum produces a rich collection of end products (1,380), the absence of which may account for hay fever.

Bottom Line

I suspect Placebo effect and poor study construction has resulted in the fuzziness for supplements and lactobacillus probiotics. The Nat.Lib.of Medicine profiles points to some specific bacteria that are low and the available studies, appear to suggest that taking those bacteria as probiotics will significantly improve hay fever. The list is:

• Bifidobacterium longum ,
• Bifidobacterium adolescentis,
• Bifidobacterium catenulatum) and
• Clostridium butyricum i.e. Miyarisan

Adequate Vitamins D and E supplementation may also help. I use the word adequate because often the dosages suggested in some studies are insufficient to alter blood level by any reasonable amount in a month (see this post for a formula ) – hence “no effect”.

There is one more path to consider, getting suggestions explicit for the shifts reports.

The results are shown below

We see L.Casei, L. Paracasei and Clostridium butyricum on the recommended list — in agreement with the above. Further down, we see Selenium (cited above) also listed

The above is evidence based on the microbiome shifts seen with hay fever.

This morning I chatted 90 minutes with another data scientist about the microbiome. After the video chat he sent me a link to this recent article: From IBS to ME – The dysbiotic march hypothesis [2020]

” The pathogenesis of the relationship is unknown. Intestinal dysbiosis may be a common abnormality, but based on 1100 consecutive IBS patients examined over a nine years period, we hypothesize that the development of the disease, often from IBS to ME, actually manifests a “dysbiotic march”. In analogy with “the atopic march” in allergic diseases, we suggest “a dysbiotic march” in IBS; initiated by extensive use of antibiotics during childhood, often before school age. Various abdominal complaints including IBS may develop soon thereafter, while systemic symptom like CFS, fibromyalgia and ME may appear years later.”

Related to the above:

• How Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Progresses: The Natural History of ME/CFS [2020]
• Can You Trust Your Gut? Implicating a Disrupted Intestinal Microbiome in the Progression of NAFLD/NASH [2020]
• Microbial transitions from health to disease [2021] “dysbiotic microbial populations may be important in the development of approaches to prevent the progression of disease and to restore health in diseased individuals.”

Personally, I have seen someone progress from GERDs to IBS to Chronic Fatigue Syndrome to atypical Crohn’s disease. The progression is not deterministic, with DNA being a significant factor.

I have had on my todo list, creating a microbiome progression map. I have just added it (based solely on gold-standards PubMed studies). It can be seen via https://microbiomeprescription.com/Library/PubMed

When you click the crystal ball . you will be taken to a new page. For example, IBS

Bottom Line

This is based on PubMed studies which are often hit and miss for depth of analysis and reporting shifts. Over time, I expect data to improve and the forecasts on this page to improve.

A Periodic Review of PubMed for COVID Fecal Microbiome finally found some studies:

One paper reported very very good results!

The optimal eight oral microbial markers (seven faecal microbial markers) were selected by fivefold cross-validation
on a random forest model, and the classifier based on the optimal microbial markers was constructed and achieved an area under the curve (AUC) of 98.06% (99.74% in the faecal microbiome).”

Alterations in the human oral and gut microbiomes and lipidomics in COVID-19 [2020]

“The heatmap showed that the faecal microbial community in CPRs (Confirmed Patients Recovered) was different from that in CPs (Confirmed Patients) and HCs,(Healthy Controls)” [SP is suspected Patient, SPR is suspected Patient recovered] which appears to confirm my hypothesis that most infections will leave a “garbage state” in the microbiome which will generally shift slowly back to the healthy state. This return to a healthy state is not certain and when it fails to happen, then we have diagnosis such as long haul covid, chronic fatigue syndrome, and post-infection syndrome.

More coming…