An Open Letter to Long COVID Clinics

The Hippocratic Oath states something that is often lost with the use of prescription medicine.

I will use those dietary regimens which will benefit my patients according to my greatest ability and judgement, and I will do no harm or injustice to them.

From US National Library of Medicine

Since the earliest days of medicine, diet was recognized as being critical aspect. This translates into regimens that benefit the microbiome. Today we have tools to do detail microbiome analysis, for example, 16S rRNA gene sequencing or shotgun sequencing.

Microbiome Shifts Reported in Long COVID

There have been multiple studies finding that the microbiome profile is associated with the severity and symptoms of an active COVID infection. Additional studies have found patterns of microbiome shifts seen in groups of people suffering from Long COVID.

  • Gut microbiota dynamics in a prospective cohort of patients with post-acute COVID-19 syndrome. Gut (Gut ) Pub: 2022 Jan 26 Epub: 2022 Jan 26 Authors Liu Q , Mak JWY , Su Q , Yeoh YK , Lui GC , Ng SSS , Zhang F , Li AYL , Lu W , Hui DS , Chan PK , Chan FKL , Ng SC 
  • Reversion of Gut Microbiota during the Recovery Phase in Patients with Asymptomatic or Mild COVID-19: Longitudinal Study. Microorganisms (Microorganisms ) Vol: 9 Issue 6 Pub: 2021 Jun 7 Epub: 2021 Jun 7 Authors Kim HN , Joo EJ , Lee CW , Ahn KS , Kim HL , Park DI , Park SK 
  • The gut microbiome of COVID-19 recovered patients returns to uninfected status in a minority-dominated United States cohort. Gut microbes (Gut Microbes ) Vol: 13 Issue 1 Pub: 2021 Jan-Dec Epub: Authors Newsome RC , Gauthier J , Hernandez MC , Abraham GE , Robinson TO , Williams HB , Sloan M , Owings A , Laird H , Christian T , Pride Y , Wilson KJ , Hasan M , Parker A , Senitko M , Glover SC , Gharaibeh RZ , Jobin C ,
  • Gut Microbiota May Not Be Fully Restored in Recovered COVID-19 Patients After 3-Month Recovery. Frontiers in nutrition (Front Nutr ) Vol: 8 Issue Pub: 2021 Epub: 2021 May 13 Authors Tian Y , Sun KY , Meng TQ , Ye Z , Guo SM , Li ZM , Xiong CL , Yin Y , Li HG , Zhou LQ
  • Gut Microbiota Interplay With COVID-19 Reveals Links to Host Lipid Metabolism Among Middle Eastern Populations. Frontiers in microbiology (Front Microbiol ) Vol: 12 Issue Pub: 2021 Epub: 2021 Nov 5 Authors Al Bataineh MT , Henschel A , Mousa M , Daou M , Waasia F , Kannout H , Khalili M , Kayasseh MA , Alkhajeh A , Uddin M , Alkaabi N , Tay GK , Feng SF , Yousef AF , Alsafar HS 

Why the Microbiome may be a critical contributor

The microbiome is essential with alterations of enzymes, metabolites, chemicals and chemical signaling affecting the entire body. Alterations will often manifest themselves as symptoms.

As the gut microbiota encode a substantively larger number of genes than its human host, it follows that they are able to undertake a variety of metabolic functions that humans are unable to do or are only able to do in a limited capacity. The gut bacteria are able to produce a variety of vitamins, synthesize all essential and nonessential amino acids, and carry out biotransformation of bile… This functionality results in the recovery of energy and absorbable substrates for the host and a supply of energy and nutrients for bacterial growth and proliferation... Associations have been established between human intestinal microbiota and a seemingly ever-increasing number of diseases, syndromes, and functional aberrations. 

The Human Gut Microbiome in Health and Disease [2014]

A Low Risk Treatment Option

Doing microbiome manipulations via dietary regimens is very much in keeping with the Hippocratic Oath. The problem is a lack of expertise in modern medical practice of doing so. The following is the recommended state-of-the-art process:

  • Obtain each patients microbiome data with a 16S rRNA gene sequencing or shotgun sequencing. This is easily available around the world – from research centers to direct-to-retail providers.
  • Determine the abnormalities from a report that will likely list 600-4000 different bacteria
  • Determine a regimen that will likely adjust these abnormalities. Often this can be done with or without prescription drugs. When prescription drugs are used, the use is definitely ‘off-label’.

The last two steps are a challenge to do. First, bacteria do not behave in a normal distribution way. Averages and standard deviations are misleading. This is illustrated below from a collection of over 2000 samples. The average is at the 84%ile, that is 84% of people will be low. People with the average amount may be having health issues from having too much.

From https://microbiomeprescription.com/Library/Statistics?taxon=165179

Unfortunately, this is not an issue that most clinical gastroenterologists are comfortable with. They neither have access to a large diffuse collections of samples, nor are skilled in the needed statistical skills to handle non-normal data.

Second, determining a regimen to address dozen of undesirable shifts is not trivial. An item that may shift one bacteria towards normal, may shift another bacteria further away from normal. This becomes what is technically known as an optimization problem involving 400-4000 bacteria by over 2000 substances known to modify some of them (according to studies on the US National Library of Medicine). A dietitian is not trained in this, nor is current on this vast number of different microbiome modifiers.

There is a Resource

The Citizen Science site, Microbiome Prescription, has collected, and make publicly available, the distributions of hundreds of bacteria from a diverse population. The site is supported by an experienced statistician who is also trained in Operations Research (the discipline that specializes in optimization problems).

Microbiome Prescription also have created a database of microbiome modifiers with the bacteria it impacts. This database identifies the source clinical study or paper for each bit of information. There are over 1.8 million records in this database.

The site is free to use as an individual. It is not complaint with Health Insurance Portability and Accountability Act (HIPAA) or European equivalents, so patients data may not be stored there. It can provide services that will process patient data through an API without saving which will usually be deemed appropriate.

The Treating Physician Dilemma

The usefulness of the above approach has not been demonstrated in any studies and thus is both novel and experimental. The approach can support a non-prescription drug, dietary regimens which will generally be recognized as safe. For example, have barley porridge with walnuts for breakfast every day, stop using stevia, eat less beef.

Returning to the oath “I will do no harm or injustice to them” raises the question – by waiting until a demonstrated approach has been published and duplicated (likely 10+ years), are you not doing both harm and an injustice?

It is very important to note that this approach is best done, patient by patient. The reason is that each patient microbiome is different, and thus the modifications will likely be different.

The site does provide a modelled, generic set of suggestions, based on the shifts reported in publish studies. These suggestions are available here.