Hypothesis Testing: 16s Results to detect SIBO

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

15% was 90%ile r over, 10% was expected
Poorer match:: 5% was over 90%ile, 10% expected

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.

ProductNamePattern
(4R,5S)-4,5,6-trihydroxy-2,3-dioxohexanoateBetween 33%ile to 66%ile
cob(II)yrinate a,c diamideBetween 66%ile to 100%ile
D-tagatoseBetween 0%ile to 33%ile
undecaprenyl phosphateBetween 0%ile to 33%ile
EndProductPattern
Vitamin B9 (Folic Acid/Folate)Between 66%ile to 100%ile
Lactic acidBetween 0%ile to 33%ile
2-ButanoneBetween 66%ile to 100%ile
Hydrogen cyanideBetween 66%ile to 100%ile
Methyl thiocyanideBetween 66%ile to 100%ile
PropionateBetween 66%ile to 100%ile
Vitamin KBetween 66%ile to 100%ile
Vitamin B7 (biotin)Between 66%ile to 100%ile
Sialic acidBetween 66%ile to 100%ile
NorepinephrineBetween 66%ile to 100%ile
EnzymeNamePattern
succinyl-CoA:acetate CoA-transferaseBetween 33%ile to 66%ile
phosphoenolpyruvate carboxykinase (GTP)Between 33%ile to 66%ile
Enzymes are a wash — all of focused on typical values
DefinitionPattern
Pentose phosphate pathway (Pentose phosphate cycle)Between 75%ile to 100%ile
Pentose phosphate pathway, oxidative phase, glucose 6P => ribulose 5PBetween 75%ile to 100%ile
Pentose phosphate pathway, non-oxidative phase, fructose 6P => ribose 5PBetween 75%ile to 100%ile
Serine biosynthesis, glycerate-3P => serineBetween 75%ile to 100%ile
Histidine degradation, histidine => N-formiminoglutamate => glutamateBetween 75%ile to 100%ile
Riboflavin biosynthesis, plants and bacteria, GTP => riboflavin/FMN/FADBetween 75%ile to 100%ile
Tetrahydrofolate biosynthesis, GTP => THFBetween 75%ile to 100%ile
CAM (Crassulacean acid metabolism), lightBetween 75%ile to 100%ile
Lysine biosynthesis, DAP dehydrogenase pathway, aspartate => lysineBetween 75%ile to 100%ile
We find high levels of glutamate, serine, lysine, ribose and ribulose being scents to look at. Unfortunately nothing was found on PubMed
tax_nametax_rankPattern
Blautia hanseniispeciesBetween 33%ile to 66%ile
Filifactor alocisspeciesBetween 66%ile to 100%ile
BacteroidiaclassBetween 66%ile to 100%ile
Bacteroides gallinarumspeciesBetween 66%ile to 100%ile
By bacteria found no strong associations


Last, we look at what studies reported

Tax RankTax NameShiftDistributionCitation Link
genusEnterococcus (NCBI:1350 )HighDistribution   📚 PubMed
genusKlebsiella (NCBI:570 )HighDistribution   📚 PubMed
genusPrevotella (NCBI:838 )HighDistribution   📚 PubMed
genusSalmonella (NCBI:590 )HighDistribution   📚 PubMed
genusStaphylococcus (NCBI:1279 )HighDistribution   📚 PubMed
genusStreptococcus (NCBI:1301 )HighDistribution   📚 PubMed
phylumFirmicutes (NCBI:1239 )LowDistribution   📚 PubMed
speciesAcinetobacter baumannii (NCBI:470 )HighDistribution   📚 PubMed
speciesBacteroides fragilis (NCBI:573 )HighDistribution   📚 PubMed
speciesBifidobacterium longum (NCBI:216816 )LowDistribution   📚 PubMed
speciesEnterococcus faecalis (NCBI:1351 )HighDistribution   📚 PubMed
speciesEnterococcus faecalis (NCBI:1351 )LowDistribution   📚 PubMed
speciesEnterococcus faecium (NCBI:1352 )HighDistribution   📚 PubMed
speciesEscherichia coli (NCBI:562 )HighDistribution   📚 PubMed
speciesEscherichia coli (NCBI:562 )HighDistribution   📚 PubMed
speciesMethanobrevibacter smithii (NCBI:2173 )HighDistribution   📚 PubMed
speciesMethanobrevibacter smithii (NCBI:2173 )HighDistribution   📚 PubMed
speciesPseudomonas aeruginosa (NCBI:287 )HighDistribution   📚 PubMed
We have some agreement, Bacteroidia is HIGH above and Firmicutes  is low.

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)

There is no clear association of this bacteria to SIBO in our samples

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

Hay Fever / Allergic Rhinitis – What we know

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]

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!

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:

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

The full details

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.

What is your NEXT diagnosis?

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:

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

on https://microbiomeprescription.com/Library/PubMed

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

Associated medical conditions to IBS
For Chronic Fatigue Syndrome
For Autism

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.

COVID Microbiome and implications for Long Haulers

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…