Over this weekend, we finally reached the threshold for citizen science to look at Autism (20+ symptom annotated uploads). This coming weekend I am attending a conference on Autism in Vancouver, British Columbia, Canada where Jason Hawrelak from Tasmania will be speaking (schedule below).

In preparation for this I decided to do a technical study comparing published studies on Autism and the results of citizen science. Is there agreement? What are the factors that come up with different results?

Video Version

Source Data

Data comes from two sources (both are subject to change with time):

• Publish Studies – listed here with citations
• Citizen Science from Microbiome Prescription – showing the distributions

We had agreement on several items, namely:

• Sutterellaceae (family) being High
• Sutterella (genus) being High
• Blautia being Low
• Bifidobacterium being High (in some Published studies)
• Lactobacillus being High (in some Published studies)

We had disagreement on only one item:

• Veillonella was high on citizen science and low on published studies

Age is a significant factor for both Bifidobacterium and Lactobacillus. Studies on autism under 6, 6-12 and older will have significantly different amounts. This may account for disagreement between published studies.

Critique of Published Studies

Reproducibility of studies is important. There are 17 Pub Med studies on the autism microbiome. If you look at Publish Studies, the same bacteria is only reported 7 times at most. Many bacteria are only reported once. Whether a bacteria is evaluated depends on the equipment being used, for example – Bilophila is reported as significant in 2 studies but Thryve 16s results do not report it.

The usual criteria is to detect statistical significance of averages between the target group and the control group. This requires some major, likely false, assumptions:

• Representative samples in each group
• Normal distribution of the bacteria in each group

A single outlier in a group can cause statistical significance to appear while a more sensitive (but require more effort) test like Pearson’s chi-squared test would find nothing to publish about. It is important to note that Pearson’s usually results in sample sizes of at least 20; many published studies do not have that number.

If I exclude non-matches with at least 2 studies with consistent results (a single study in 17 studies is likely unreliable), then we have the following not detected yet with Citizen Science (which have barely enough studies to do any analysis).

Collinsella

Corynebacterium

Desulfovibrio

Dialister

Parabacteroides

Prevotella

Sarcina

On the flip side, Citizen Science reports on some bacteria not reported in published studies over 10 with high significance.

DNA SNPs and Microbiome Interaction

The microbiome and the person’s DNA interacts. Specific SNP issues are expected to manifest themselves in a person’s microbiome. This adds another level of complexity.

Bottom Line

Large representative samples and in depth skilled statistical analysis is needed to reliably identify the bacteria associated with a symptom, medical condition or characteristic.

From Publish Studies and Citizen Science, we have apparent agreement on 5 taxa, disagreement on 1, and silence in terms of repeatability on some 20 additional ones. I hope/ believe that as the number of samples in Citizen Science data set grows we will find more agreement with some of the published studies.

Below is a spreadsheet for interested parties.

References

1. The Gut Microbiota and Autism Spectrum Disorders
   Frontiers in Cellular Neuroscience (Front Cell Neurosci ) Vol: 11 Issue Pages: 120
   Pub: 2017 Apr 28 Epub: 2017 Apr 28 Authors Li Q , Han Y , Dy AB , Hagerman RJ ,
2. New evidences on the altered gut microbiota in autism spectrum disorders.
   Microbiome (Microbiome ) Vol: 5 Issue 1 Pages: 24
   Pub: 2017 Feb 22 Epub: 2017 Feb 22 Authors Strati F , Cavalieri D , Albanese D , De Felice C , Donati C , Hayek J , Jousson O , Leoncini S , Renzi D , Calabrò A , De Filippo C ,
3. Distinct Microbiome-Neuroimmune Signatures Correlate With Functional Abdominal Pain in Children With Autism Spectrum Disorder.
   Cellular and molecular gastroenterology and hepatology (Cell Mol Gastroenterol Hepatol ) Vol: 3 Issue 2 Pages: 218-230
   Pub: 2017 Mar Epub: 2016 Dec 11 Authors Luna RA , Oezguen N , Balderas M , Venkatachalam A , Runge JK , Versalovic J , Veenstra-VanderWeele J , Anderson GM , Savidge T , Williams KC ,
4. The valproic acid rat model of autism presents with gut bacterial dysbiosis similar to that in human autism.
   Molecular autism (Mol Autism ) Vol: 9 Issue Pages: 61
   Pub: 2018 Epub: 2018 Dec 10 Authors Liu F , Horton-Sparks K , Hull V , Li RW , Martínez-Cerdeño V ,
5. Analysis of gut microbiota profiles and microbe-disease associations in children with autism spectrum disorders in China.
   Scientific reports (Sci Rep ) Vol: 8 Issue 1 Pages: 13981
   Pub: 2018 Sep 18 Epub: 2018 Sep 18 Authors Zhang M , Ma W , Zhang J , He Y , Wang J ,
6. Fecal microbiota and metabolome of children with autism and pervasive developmental disorder not otherwise specified.
   PloS one (PLoS One ) Vol: 8 Issue 10 Pages: e76993
   Pub: 2013 Epub: 2013 Oct 9 Authors De Angelis M , Piccolo M , Vannini L , Siragusa S , De Giacomo A , Serrazzanetti DI , Cristofori F , Guerzoni ME , Gobbetti M , Francavilla R ,
7. Identifying psychiatric disorder-associated gut microbiota using microbiota-related gene set enrichment analysis.
   Briefings in bioinformatics (Brief Bioinform ) Vol: Issue Pages:
   Pub: 2019 Apr 5 Epub: 2019 Apr 5 Authors Cheng S , Han B , Ding M , Wen Y , Ma M , Zhang L , Qi X , Cheng B , Li P , Kafle OP , Liang X , Liu L , Du Y , Zhao Y , Zhang F ,
8. Altered composition and function of intestinal microbiota in autism spectrum disorders: a systematic review.
   Translational psychiatry (Transl Psychiatry ) Vol: 9 Issue 1 Pages: 43
   Pub: 2019 Jan 29 Epub: 2019 Jan 29 Authors Liu F , Li J , Wu F , Zheng H , Peng Q , Zhou H ,
9. Microbiota-related Changes in Bile Acid & Tryptophan Metabolism are Associated with Gastrointestinal Dysfunction in a Mouse Model of Autism.
   EBioMedicine (EBioMedicine ) Vol: 24 Issue Pages: 166-178
   Pub: 2017 Oct Epub: 2017 Sep 21 Authors Golubeva AV , Joyce SA , Moloney G , Burokas A , Sherwin E , Arboleya S , Flynn I , Khochanskiy D , Moya-Pérez A , Peterson V , Rea K , Murphy K , Makarova O , Buravkov S , Hyland NP , Stanton C , Clarke G , Gahan CGM , Dinan TG , Cryan JF ,
10. Intestinal Dysbiosis and Yeast Isolation in Stool of Subjects with Autism Spectrum Disorders.
    Mycopathologia (Mycopathologia ) Vol: 182 Issue 3-4 Pages: 349-363
    Pub: 2017 Apr Epub: 2016 Sep 21 Authors Iovene MR , Bombace F , Maresca R , Sapone A , Iardino P , Picardi A , Marotta R , Schiraldi C , Siniscalco D , Serra N , de Magistris L , Bravaccio C ,
11. Ketogenic diet modifies the gut microbiota in a murine model of autism spectrum disorder.
    Molecular autism (Mol Autism ) Vol: 7 Issue 1 Pages: 37
    Pub: 2016 Epub: 2016 Sep 1 Authors Newell C , Bomhof MR , Reimer RA , Hittel DS , Rho JM , Shearer J ,
12. Can we reduce autism-related gastrointestinal and behavior problems by gut microbiota based dietary modulation? A review.
    Nutritional neuroscience (Nutr Neurosci ) Vol: Issue Pages: 1-12
    Pub: 2019 Jun 19 Epub: 2019 Jun 19 Authors Nogay NH , Nahikian-Nelms M ,
13. The Role of Gut Microbiota in Gastrointestinal Symptoms of Children with ASD.
    Medicina (Kaunas, Lithuania) (Medicina (Kaunas) ) Vol: 55 Issue 8 Pages:
    Pub: 2019 Jul 26 Epub: 2019 Jul 26 Authors Martínez-González AE , Andreo-Martínez P ,
14. Association Between Gut Microbiota and Autism Spectrum Disorder: A Systematic Review and Meta-Analysis.
    Frontiers in psychiatry (Front Psychiatry ) Vol: 10 Issue Pages: 473
    Pub: 2019 Epub: 2019 Jul 17 Authors Xu M , Xu X , Li J , Li F ,
15. Analysis of gut microbiome, nutrition and immune status in autism spectrum disorder: a case-control study in Ecuador.
    Gut microbes (Gut Microbes ) Vol: Issue Pages: 1-12
    Pub: 2019 Sep 18 Epub: 2019 Sep 18 Authors Zurita MF , Cárdenas PA , Sandoval ME , Peña MC , Fornasini M , Flores N , Monaco MH , Berding K , Donovan SM , Kuntz T , Gilbert JA , Baldeón ME ,
16. Increased abundance of Sutterella spp. and Ruminococcus torques in feces of children with autism spectrum disorder.
    Molecular autism (Mol Autism ) Vol: 4 Issue 1 Pages: 42
    Pub: 2013 Nov 4 Epub: 2013 Nov 4 Authors Wang L , Christophersen CT , Sorich MJ , Gerber JP , Angley MT , Conlon MA ,
17. Characterization of Intestinal Microbiota and Probiotics Treatment in Children With Autism Spectrum Disorders in China.
    Frontiers in neurology (Front Neurol ) Vol: 10 Issue Pages: 1084
    Pub: 2019 Epub: 2019 Nov 5 Authors Niu M , Li Q , Zhang J , Wen F , Dang W , Duan G , Li H , Ruan W , Yang P , Guan C , Tian H , Gao X , Zhang S , Yuan F , Han Y ,
18. Autism spectrum disorder is associated with gut microbiota disorder in children.
    BMC pediatrics (BMC Pediatr ) Vol: 19 Issue 1 Pages: 516
    Pub: 2019 Dec 27 Epub: 2019 Dec 27 Authors Sun H , You Z , Jia L , Wang F ,
19. An approach to gut microbiota profile in children with autism spectrum disorder.
    Environmental microbiology reports (Environ Microbiol Rep ) Vol: Issue Pages:
    Pub: 2019 Nov 11 Epub: 2019 Nov 11 Authors Andreo-Martínez P , García-Martínez N , Sánchez-Samper EP , Martínez-González AE ,
20. [Correlation between gut microbiota and behavior symptoms in children with autism spectrum disorder].
    Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics (Zhongguo Dang Dai Er Ke Za Zhi ) Vol: 21 Issue 7 Pages: 663-669
    Pub: 2019 Jul Epub: Authors Zhao RH , Zheng PY , Liu SM , Tang YC , Li EY , Sun ZY , Jiang MM ,

For people not aware of the Microbiome Prescription site, this gives an overview.

Hello, a few months ago I saw a comment at the ME-Research Forum in which a sick commented that a doctor in Spain is prescribing hidroaltesona to the sick as palliative treatment for the ME.
I have tried to investigate about it since I have been taking 10 mg of hidroaltesona daily for a year having improved my intestinal problems (swelling and diarrhea, about 6 times a day in the last 15 years) passing to a Normal frequency.
My doctor put me the treatment for hipocortisolismo but the intestinal improvement was immediate.
Do you know studies or testimonies of people who have maintained this long-term treatment? 

From a reader

Hidroaltesona [C₂₁H₂₉Na₂O₈P] is related to Cortisol [
C₂₁H₃₁O₈P] (chemically different) containing two sodium atoms. Searching PubMed did not find any studies — I have never seen this happen before! I checked Hydrocortisone [C₂₁H₃₀O₅] and found studies but the absence of sodium and phosphate atoms left me with a feeling that it was only vaguely similar.

From Manufacturer Site

All indications of oral corticotherapy, except in states that involve life-threatening and require intravenous route. The most important ones are:

• Replacement therapy in primary or secondary adrenocortical insufficiency.
• Congenital adrenal hyperplasia.

Other indications are:

• Rheumatic and collagen diseases: treatment of exacerbations and / or maintenance therapy of rheumatoid arthritis, juvenile arthritis, ankylosing spondylitis and psoriatic arthritis when conservative treatments have been shown ineffective; Polymyalgia rheumatica; acute rheumatic fever; systemic lupus erythematosus; severe dermatomyositis; noia periarteritis; cranial arteritis and Wegener’s granulomatosis; scleroderma and dermatomyositis.
  
• Dermatological diseases: allergic eczema, bullous pemphigoid pemphigus, generalized exfoliative dermatitis, severe erythema multiforme, erythema nodosum and severe psoriasis.
• Serious allergic diseases: allergic rhinitis, contact dermatitis and bronchial asthma refractory to conventional therapy.
• Lung diseases: sarcoidosis with pulmonary disease, extrinsic allergic alveolitis (organic dust pneumoconiosis), desquamative interstitial pneumonia (idiopathic pulmonary fibrosis).
• Eye pathology: keratitis, choroiditis, chorioretinitis, iritis and iridocyclitis.
• Hematological diseases: idiopathic thrombocytopenia, hemolytic anemias and palliative treatment of leukemia and lymphomas.
• Gastrointestinal and hepatic pathology: ulcerative colitis, Crohn’s disease and hepatitis.

More Information

I found some experience from MDs with it at https://www.doctoralia.es/medicamentos/hidroaltesona/preguntas

That may be the best source to get solid information.

• “long-term corticosteroid treatments, and depending on the dose, can induce changes and side effects in practically the entire economy of the organism, affecting almost any “
• “What is the relationship between hydroaltesona and prednisone? Both active ingredients are corticosteroids, with different potency and are used in many processes and diseases. “
• ” In principle, in adrenal insufficiency, the doses range between 25 and 40 mg per day. ” – so this patient is on a low dosage.

PubMed on Hydrocortisone and ME/CFS

• ” Cortisol levels, before or after dex, did not differ between CFS and Healthy Controls (HCs). Cortisol levels were more variable in CFS than HCs. ” [2018]
• ” we found an inverse relationship between cortisol reactivity and symptom severity. There was no relationship between cortisol reactivity and illness duration. ” [2016]

• Low-dose Hydrocortisone in Chronic Fatigue Syndrome: A Randomised Crossover Trial [1999] ” Interpretation: In some patients with chronic fatigue syndrome, low-dose hydrocortisone reduces fatigue levels in the short term. Treatment for a longer time and follow-up studies are needed to find out whether this effect could be clinically useful. “
• ” The anti-inflammatory effect of cortisone at an adequate dose has, to my knowledge, not been investigated so far. I am left with the impression that the potential effect of cortisone on myalgic encephalopathy / chronic fatigue syndrome has been rejected on the basis of three studies that have investigated only low-dose hydrocortisone therapy of an hypocortisolism presumed and which are believed to have too little potency to conclude. with something. ” [2016]

Bottom Line

This drug is prescribed for ulcerative colitis, Crohn’s disease and is known to impact the entire body. We know that it inhibits many bacteria (list here).

Checking predictions on this page, it is predictive to help ME/CFS without IBS, but worsen ME/CFS with IBS and basic CFS. On the flip side, it is predictive to help IBS. The predictions are based on a naive estimate of it’s impact on the many reported shifts with these conditions.

I have often been asked that question. The general answer is “it depends”. This post gives you a science based answer.

Enter the probiotic Mixture

Once you are logged in, a new item appears on the menus as shown below

On the next screen enter a name (including the provider), for example

Now go back and get your suggestions.. What you just entered will be shown,

Bottom Line

A simple process. If you have your thryve (or other providers) custom probiotic mixtures handy, run them thru add add the results as a comment on this page.

A reader asked me to compile a list of of published studies and articles on the use of antibiotics with ME/CFS. Note that with gut dysbiosis as the model, the choice of antibiotics may depend on the details of the dysbiosis (this a 16s or shotgun GI report is suggested. Xenogene.es offers excellent reports).

At the Whittemore Peterson Institute (WPI) is a non-profit medical research institute dedicated to the support of those with a spectrum of neuro-immune diseases (NIDs) including: myalgic encephalomyelitis, (ME), fibromyalgia, and similar complex chronic diseases of the immune system and the brain. Dr. De Meirleir earned his medical degree from the Vrije Universiteit Brussel in 1977, and completed an internal medicine residency in the Department of Internal Medicine, University Hospital of Vrije Universiteit Brussel. His current research focuses on a subgroup of ME patients who show evidence of chronic bacterial infection and gut dysbiosis. These patients are responding to specific antibiotic/ probiotic therapy.

http://nvcbr.org/portfolio-items/kennydemeirleir/

• Azithromycin in Chronic Fatigue Syndrome (CFS), an Analysis of Clinical Data (2006) ” Results: Of the 99 patients investigated, 58 reported a decrease in the symptoms by the use of azithromycin.”
• Open-label Pilot for Treatment Targeting Gut Dysbiosis in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Neuropsychological Symptoms and Sex Comparisons (2018) ” Large treatment ( alternate weeks of Erythromycin (400 mg of erythromycin as ethyl succinate salt) twice daily ) effects were observed for the intention-to-treat sample with a reduction in Streptococcus viable count and improvement on several clinical outcomes including total symptoms, some sleep (less awakenings, greater efficiency and quality) and cognitive symptoms (attention, processing speed, cognitive flexibility, story memory and verbal fluency).  “
• Chronic Fatigue Syndrome After Q Fever (2007) ” After 4-12 months they developed post-Q-fever fatigue syndrome and were treated with intracellular active antibiotics (fluoroquinolones and tetracycline) for 3-12 months. Efficacy of the treatment was observed in two patients, but in one patient the results were not encouraging. “
• Sleep Quality and the Treatment of Intestinal Microbiota Imbalance in Chronic Fatigue Syndrome: A Pilot Study (2015) ” Participants were administered erythromycin 400 mg b.d. for 6 days… Short term antibiotic treatment appears to be insufficient to effect sustainable changes in the gut ecosystem in most CFS participants. Some improvement in objective sleep parameters and mood were found in participants with reduced levels of gram-positive gut microbiota after antibiotic treatment, which is encouraging. Further study of possible links between gut microorganisms and sleep and mood disturbances is warranted. “
• On the Question of Infectious Aetiologies for Multiple Sclerosis, Schizophrenia and the Chronic Fatigue Syndrome and Their Treatment With Antibiotics (2009)… ” in the beginning of 2007 two female patients suffering from severe and long standing chronic fatigue syndrome were added. The first of them, after sixty days of treatment with antibiotics showed excellent treatment results on follow-up one year later, whereas the second, who also took the combination of antibiotics for sixty days, was rated as having shown a significant improvement. “
• Mycoplasma Blood Infection in Chronic Fatigue and Fibromyalgia Syndromes (2003) ” Most patients with CFS/FMS who have mycoplasma infection appear to recover and reach their pre-illness state after long-term antibiotic therapy with doxycycline, and the infection can not be detected after recovery.  “
• ” Dr. Nicolson suggests long-term antibiotic treatment with drugs such as doxycycline, cyprofloxacin, azithromycin, or clarithromycin. By long-term he means a continuous 6-month course of antibiotics followed by multiple 6-week cycles. The extended antibiotic treatment is needed because of “the intracellular locations of mycoplasmas… the slow-growing nature of these infections, their inherent insensitivity to most antibiotics and the persistence of the infections in metabolically inactive forms.” [Src]
  • High prevalence of Mycoplasma infections among European chronic fatigue syndrome patients. Examination of four Mycoplasma species in blood of chronic fatigue syndrome patients (2002)
• Role of Rickettsiae and Chlamydiae in the Psychopathology of Chronic Fatigue Syndrome (CFS) Patients (2000) Results: Group one: 79.5% good and very good results; 4.1% fairly good; 16.4% failed. Group two: 82.3% good and very good results; 2.5% fairly good; 15.2% failed. … All of the Dr. Bottero’s therapeutic results are confirmed since 1991 by Dr. Cecile Jadin of Randburg (South Africa) for more than 3000 CFS and other psychopathological states (300): Sydney 98 CFS Conference, Australia.

A treatment plan (Cecile Jadin’s is similar)

Treatment with antibiotics is difficult because drugs have to penetrate the host cell wall as well as the intracellular organisms. Treatment needs to be prolonged and pulsed, because of continual replication of the intracellular forms. Until adequate diagnostic facilities are readily available treatment needs to be in two stages: the first stage, which is diagnostic, involves the use of two long-term bacteriostatic antibiotics for 6 weeks, and the second, meant to be curative, involves the introduction of a third bactericidal antibiotic.

One possible choice of antibiotics for the first stage is a combination of Doxycycline and Azithromycin. Initially, the Doxycyline needs to be given alone in low dosage for two weeks, because of the risk of a Herxheimer reaction resulting from the release of toxins by damaged bacteria. Such reactions are usually mild and short-lived. If stable after two weeks, Azithromycin in low dosage is added for 4 weeks. Roxithromycin can be used in place of Azithromycin. . Improvement of symptoms, or the occurrence of a Herxheimer reaction, confirms the diagnosis.

Chronic fatigue syndrome or myalgic encephalomyelitis (2007) in British Medical Journal

From Published Books

Bottom Line

There is a high success rate reported with antibiotics. Recent research suggests that the failures may be selection of inappropriate antibiotics for the person’s specific gut dysbiosis. IMHO, a 16s or shotgun (Xenogene) microbiome report should be done and carefully analyzed prior to selecting the various antibiotics needed.

The microbiomePrescription site supports evaluation of antibiotics against a microbiome, as well as other prescription drugs.

Unfortunately, there has been only one comprehensive study done, so relative ranking may not apply for many samples (i.e. do a show all and scan for the ones that are most acceptable)

With hand-picking against ME/CFS profiles, results can get quite good. All of the antibiotics involved with prior successful treatment were listed.

A reader wrote me asking about the different theories of ME/CFS, and I just read Cort’s The Best, the Most, the Strangest and the Worst of 2019 in ME/CFS and Fibromyalgia. I have used different models over the years (going with the best available usually). Often it seems that both patients and researchers are lost in the forest strictly following a compass bearing and crossing over paths (and ignoring) that may lead them out of the forest.

My academic training is modelling. A model is a hypothesis with some extra criteria:

• Must be predictive
• Must be testable
• Must explain existing observations
• Should be as simple as possible

A good model is one that explains more observations than other models. A good model is one that is easy to test. A good model predicts possible findings (which if the findings comes in correct, confirms the model).

The most challenging set of observations

The following is known to every ME/CFS patient and treating physician: The huge variation of symptoms. For a list of non-lab symptoms, see MEpedia Page, CDC Page, Review of the Evidence on Other ME/CFS Symptoms and Manifestations, and Review of the Evidence on Major ME/CFS Symptoms and Manifestations.

We know that DNA/SNP plays a role – for example, ME/CFS people have smaller hearts, craniocervical instability and certain DNA mutations are more common. These are not causes (people with the same items do not have ME/CFS) but contributing factors that makes people more disposes to developing ME/CFS. Think of the “Perfect Storm”, you have a sea worthy boat — unfortunately you motor died in the middle of gale when you were close to a reef…. a series of unfortunate events.

My criteria for a hypothesis that has merit to investigate or fund — it must give an explanation for the different symptoms! A common response is there are different subsets and we need to identify each subset first, or ‘we have not had time to investigate that yet’ (and likely will never) or even a truthful, “I don’t know” or perhaps a dismissive “that’s not relevant”.

The Microbiome Model explains Symptoms

A rhetoric question — if all of your ME/CFS symptoms disappear do you have ME/CFS. At one time remission was defined as no longer having the minimum number of symptoms required for the CDC definition.

About a seven months ago, I tossed up an analysis page on symptoms to bacteria expecting weak results. I was shocked, Eureka! Specific bacteria are associated with specific conditions and symptoms. Since then the database have grown and the number of people entering symptoms have increased.

Alcohol Intolerance

This occurs in a very high percentage of M/E CFS patients. Our analysis found that there were specific microbiome shifts (high levels of certain bacteria)

Neurological: Difficulty reading

We find similar patterns, and can drill down to higher resolution (because of more data) and see a strong clustering with people with the highest 15% of some bacteria.

Neurocognitive: Difficulty paying attention for a long period of time

As we walk thru them, we notice overlaps of some bacteria. Look at what is below and alcohol intolerance above. We see the following in common

• Butyricimonas (genus)
• Deltaproteobacteria (class)
• Desulfovibrionales (order)

These are the main players for some ME/CFS, the other bacteria likely cooperate with them to produce specific symptoms (which often have a DNA requirement to appear).

I should point out that a P-value of 0.05 or below is often the criteria for getting a finding published in a medical journal. Some of the values we came up with are 0.000194 and lower. Much much stronger evidence than is usually seen.

Summary

The criteria are below:

• Must be predictive
• Must be testable
• Must explain existing observations
• Should be as simple as possible

The microbiome model beats everything else (please add detail comments if you disagree of which model is better using these criteria).

This model is predictive, it can take a microbiome sample in and based on the content alone predict probable symptom (key word is probable) which from my own experience and other user feedback seems around 75% accurate.

This mode is testable, from a microbiome sample we can determine a list of items that would probably help. Some people have had outstanding results. Again, the key word is probable.

This model explain existing observations, the observations we used above in symptoms. Recent research studies also find that it explains many lab results seen with ME/CFS.

This model is simple to understand. It is a beast to work with because of the number of bacteria involved.

The last issues for me are treatment-actionable and available. Most of the research hypothesis do not have treatments to address the cause. A few that do are usually not available — often because it is a research protocol and not “standard of medical care” .. i.e. no one can use, especially the ordinary family physician sitting in a community clinic in the Australian Outback!

The microbiome can be manipulated without prescription drugs which removes the stumbling block of “standard of medical care”. It can even be done under quasi-medical supervision if a patient uses available tools and present the suggestions to their physician for review. Getting physicians up to speed on the microbiome is a different issue.

If you believe a different model is better — then please provide the details in the comments. I am open to changing models.