Dr Igor Markov Says ME/CFS Is Caused by a Bacterial Dysbiosis in the Kidneys, and Says Autovaccine Therapy Cures 93% of ME/CFS Cases

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Dr Markov's NephroDysbacteriosis / CBIS Theory of ME/CFS

Dr Igor Markov in the Ukraine has an incredible theory on the cause of ME/CFS, and also a unique ME/CFS treatment which he claims is fully curative in 93% of ME/CFS cases. Curative means all the symptoms of ME/CFS fully and permanently disappear after the course of treatment is complete, and no further treatment is required to maintain full remission.

Dr Markov has published details of his theory and ME/CFS treatment in this journal article. Extract of this article here:
We, Markov Igor S and Markov Artem I, present you the research work (the study/manuscript) "Chronic Bacterial Intoxication Syndrome under the mask of CFS/ME" about the never & nowhere before-published unique original results of the almost 12-years (2009-2020) systematic clinical research of the true etiology of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ ME);

about the new revolutionary previously unknown diagnosis Chronic Bacterial Intoxication Syndrome (CBIS) that gives such a long-awaited in-depth clinical understanding and discovery of the true basic etiological and pathogenetic causes of the long-known and worldwide-spread, but still etiologically mysterious CFS/ME;

about clinical prompt diagnostics and unique successful methods of treatment of CBIS (treated more than 4500 patients: children-2160, adults-2340), hidden till the moment being under the mask of CFS/ME.

The search for the true origin and causes of CFS, which are globally associated mainly with the chronic EBV-infection, was started by our clinics back in 2005 after 5 years of unsuccessful attempts to achieve positive results with intensive anti-viral therapy. It took 10 long years, in order to the authors themselves could believe in what it seemed impossible to believe.

In all patients with typical features of CFS there was revealed a focus of chronic bacterial infection in the kidneys, which more often remained clinically locally asymptomatic and was called Nephro dysbacteriosis.

Bacteria toxins, that were extracted from urine, persisted in the kidneys for years and decades and caused severe often long-term intoxication and led to the development of a pathological condition that till the moment being is called CFS.

So appeared a new previously unknown diagnosis chronic bacterial intoxication syndrome (CBIS) which etiologically and pathogenetically really reflects the diversified (symptomatically often multidisciplinary) clinic of this disease.

The severity of intoxication often made the life of patients simply insufferable, therefore 28% of adults and even 1.4% of children experienced suicidal thoughts. Intoxication grade was confirmed by toxicological blood investigation.

The treatment of the patients with CBIS was successfully carried out by bacterial auto vaccines without traditional (“according to the Protocol”) prescribing of antibiotics.

Moreover, it was found that in at least 90% of patient’s nephron dysbacteriosis [dysbiosis] and CBIS had developed precisely after thoughtless, expansive and aggressive antibiotic therapy, which often began in childhood.

Taking into consideration in fact global treatment by antibiotics, how many people worldwide are really suffering from nephron dysbacteriosis and CBIS, not receiving adequate treatment?

All clinical paths of removing the mask from CFS and of diagnostical transformation of CFS into CBIS is described consequentially and argumentally in the cycle of 9 reports/articles on clinical diagnosis, on bacteriological and toxicological diagnosis and treatment of CBIS.

Below you find the first part of whole study “chronic bacterial intoxication syndrome under the mask of CFS/ME”, namely Reports 1.-6. “Clinical diagnosis”.

The second part of the study (Reports 7-9.) will contain data on bacteriological diagnosis (Report 7), toxicological diagnosis (Reports 8) and treatment of CBIS (Report 9). It’s ready for publication and now some data are being translated in English.

And else: the current urgent situation with SARS-CoV-2 (Covid-19) is considered as an acute pandemic. But CFS/ME, correctly called as CBIS, which also do not recognize geographical boundaries and reap their deadly harvests during decades of proliferation in the world (the officially registered CFS number is up to 1% of global population, i.e. about 70-80 million people), can be courageously considered as a global infectious disease and a chronic pandemic, the fight against which remains no less urgent.

And if humanity will be saved from Covid-19 by anti-SARS-CoV-2 vaccines, we believe that we have invented such a vaccine against disease called by us CBIS, hidden under the mask of CFS/ME.



Source: Chronic bacterial intoxication syndrome under the mask of CFS/ME. 15-16 February 2021. Journal of Infectious Diseases & Preventive Medicine.

His brother Dr Oleg Markov has commented about the theory and treatment in a Phoenix Rising Q&A thread. This post is a summary of all the important info that Dr Oleg Markov posted. References to Oleg Markov's original statements are given in the 1 symbol weblinks at the end of each paragraph below.

Another thread discussing Dr Markov's CBIS theory of ME/CFS, and where Phoenix Rising members are posting the results of their urine bacterial culture tests and their progress on autovaccine therapy, can be found HERE.



Introduction

Dr Igor Markov in Kyiv (Kiev), Ukraine says he has discovered the cause of ME/CFS: he says ME/CFS is caused by a bacterial dysbiosis in the kidneys, a condition he has named nephrodysbacteriosis.

"Dysbacteriosis" and "dysbiosis" mean an imbalance or overgrowth of bacteria.

Dr Markov discovered this kidney dysbiosis constantly releases bacterial toxins into the bloodstream, causing a body-wide toxic condition he has named the chronic bacterial intoxication syndrome (CBIS). He says this kidney dysbiosis leads to CBIS, which in turn causes ME/CFS.

Dr Markov says nephrodysbacteriosis is a previously unknown medical condition that he himself discovered.

Nephrodysbacteriosis is an imbalance or overgrowth of bacteria in the kidney, which is not quite the same as a regular kidney infection (pyelonephritis) or a regular urinary tract infection. Nephrodysbacteriosis would be more analogous to intestinal dysbiosis.

Dr Markov says this kidney dysbiosis is locally asymptomatic, and unlike a regular kidney infection, produces no local inflammatory response in the kidney.

Markov believes nephrodysbacteriosis causes ME/CFS, because when he treats the nephrodysbacteriosis in ME/CFS patients, he finds nearly all patients are cured of their ME/CFS.

To treat nephrodysbacteriosis, Dr Markov has pioneered the use of autovaccine therapy. He says this autovaccine treatment is fully curative for 93% of the ME/CFS patients he has treated.

Autovaccines are a medical technology which date back to 1900, in the pre-antibiotic era. These vaccines work by injecting the patient with their own killed bacteria, in order to stimulate an immune response to target those bacteria. A Wikipedia article on autovaccines here.

Using a special high sensitivity urine test, Dr Markov isolates and identifies the bacterial species causing nephrodysbacteriosis in the kidneys. From these live bacteria, he creates an autovaccine. An autovaccine consists of the isolated bacteria which have been heat or chemically killed to render them safe for injection. Dr Markov then gives ME/CFS patients several courses of injections with this autovaccine. He says this autovaccine therapy gradually fixes the nephrodysbacteriosis, which in turn permanently cures the ME/CFS.

Before the antibiotics era, autovaccines were utilized to treat some infections in humans; but these days autovaccines are mostly employed for infections of livestock. Autovaccines are also called autogenous vaccines or autologous vaccines.

Dr Markov discovered that antibiotics have no long-term efficacy for treating nephrodysbacteriosis (and finds antibiotics can actually make the kidney dysbiosis worse). But by using autovaccines to stimulate the immune system to mount a targeted attack on the specific bacteria causing the kidney dysbiosis, Dr Markov finds his autovaccine therapy cures the dysbiosis, and this in turn cures ME/CFS.

Dr Igor Markov has treated 4288 ME/CFS patients (children and adults) with his autovaccine therapy from the period 2009 to 2021, and reports that 93% of his patients with nephrodysbacteriosis achieved a full and permanent recovery from ME/CFS (although he says some patients may relapse after 5 to 7 years, but this can be fixed with additional autovaccine therapy). 1 2

Dr Markov says that with the autovaccine therapy, it takes 6 months to 2-3 years to achieve full recovery from ME/CFS, with patients who have been ill longer requiring a longer autovaccine treatment.

Dr Markov started his research on ME/CFS in 2005. After 5 years of unsuccessful attempts to achieve positive results with anti-viral therapy, Dr Markov took a different direction, and started to explore autovaccine treatments.

Dr Markov wrote that it took 10 years of successful autovaccine treatments on thousands of ME/CFS patients before he could finally believe what seemed impossible to believe: that autovaccines can cure ME/CFS. 1 So even Dr Markov was initially skeptical of his own ME/CFS theory and treatment, and it was only after 10 years of successful treatments that he became convinced that it really does work.



Links to Dr Markov's Websites, Social Media, and Reviews

Dr Igor Markov and his son Dr Artem Markov run the Vitacell Clinic and Markov Clinic (two different clinics in Kyiv).

Relevant info from Dr Markov's website:
Social Media:
Relevant YouTube videos by Dr Markov (videos have English subtitles):
Published scientific material:
Other CBIS papers from Dr Markov, which are available to buy here:
  • CBIS. Bacteriological diagnosis (Report 7)
  • CBIS. Toxicological diagnosis (Report 8)
  • CBIS. Treatment (Report 9)
Reviews of Dr Markov's CBIS theory of ME/CFS
Vaccine patents
  • Dr Markov's vaccine patents here.


Nephrodysbacteriosis as the Cause of ME/CFS

Dr Igor Markov says he has discovered a new medical condition involving bacterial dysbiosis in the kidneys, which he has named nephro-dysbacteriosis. This dysbiosis of the kidney is locally asymptomatic (does not cause any local inflammation), and is due to a disorder of the local mucosal immunity on the kidney mucous membranes, which allows bacteria to proliferate.

Historically the urine and urinary tract have been considered to be normally sterile, but in fact we now know the urinary tract does contain a microbiome (see this paper).

Dr Markov says once nephrodysbacteriosis occurs in the kidneys, it results in bacterial toxins (like LPS and bacterial exotoxins) entering into the bloodstream. As these toxins enter the blood, Dr Markov says they cause a condition he names chronic bacterial intoxication syndrome (CBIS). 1

There is some support for this idea, as blood plasma LPS levels were found to be raised in ME/CFS patients in Dr Maureen Hanson's study, so certainly there appears to be a bacterial source somewhere in ME/CFS patients which leaks endotoxin (LPS) into the blood.

And research from Prof Michael Maes suggests that LPS entering the bloodstream from a leaky gut may play a role in ME/CFS.

Dr Markov believes that the kidneys have far greater propensity for leaking bacterial toxins into the bloodstream than the intestines and a leaky gut, due to the fact that 2000 liters of blood pass through the kidneys daily for filtration purposes, which tends to wash bacterial toxins produced in the kidneys into the systemic blood circulation. 1

Furthermore, blood passing through the intestines is filtered by the first-pass metabolism in the liver, which is known to remove 95% to 99% of any LPS, and presumably removes other bacterial toxins too. But blood going through the kidneys is not routed via the first-pass metabolism, so is not filtered of its bacterial toxins.

Note though that endotoxin (LPS) is not the only bacterial toxin that Dr Markov says is involved with CBIS. Dr Markov often finds Enterococcus, Staphylococcus and Streptococcus in nephrodysbacteriosis, and these gram-positive bacteria do not produce endotoxin, but produce various exotoxins.

For example, we will see later that Enterococcus is the most common cause of nephrodysbacteriosis, and some strains of this bacterium produce a toxin called Enterococcus cytolysin (a cytolysin is a substance toxic to cells). Another example is the exotoxin called enterotoxin B made by Staphylococcus, which has very harmful effects upon the immune system, 1 and may play a major role in the triggering of autoimmunity. 1

As an etiological theory of the complex multi-system disease that is ME/CFS, the idea that bacterial toxins entering the bloodstream could cause ME/CFS makes intuitive sense. Although Dr Markov proposes these bacterial toxins come from one location (the kidneys), once they enter the systemic circulation, these toxins have the potential to harm every organ and every bodily system. So such toxemia from a bacterial dysbiosis in one organ may go a long way to explaining the multi-system aspect of ME/CFS.



Prevalence of Nephrodysbacteriosis and CBIS in ME/CFS

Dr Igor Markov finds CBIS (and so presumably also nephrodysbacteriosis) in more than 95% of ME/CFS patients who satisfy the CDC 1994 Fukuda criteria. By contrast, in 70 adult healthy controls, Dr Markov found only 7% have nephrodysbacteriosis. 1 2

He finds antibiotics are not effective at permanently curing the nephrodysbacteriosis: he says antibiotics may result in a short-term positive effect, but in the long term, may actually worsen the dysbiosis in the kidneys, making the CBIS worse. 1

Some Phoenix Rising members reading Dr Oleg Markov's posts have speculated that the autovaccine might also have an antibacterial effect in the intestines as well as the kidneys; but Dr Oleg Markov says "we have not detected a noticeable influence of autovaccines on the balance of the intestinal bacterial flora, although, perhaps, this issue requires additional study". 1 So this is one reason why Dr Markov believes the kidneys habor the dysbiosis.

Dr Markov says nephrodysbacteriosis can arise when Enterococcus or Enterobacter bacteria from the intestines translocate into the kidneys; or when Staphylococcus or Streptococcus from the nasopharynx translocate into the kidneys (the nasopharynx is the area just above the back wall of the throat). 1

So some of the bacteria which the autovaccines target are also found in other areas of the body, like the nasopharynx and the intestines, and the autovaccines could thus in principle have effects in these other areas too, as well as in the kidneys. But Dr Markov believes the autovaccines target dysbiosis in the kidneys.

Note that Dr Markov finds nephrodysbacteriosis and CBIS is not unique to ME/CFS. So we might speculate that nephrodysbacteriosis may not be the sole cause of ME/CFS, but may cause ME/CFS in conjunction with other factors (such as a chronic viral infection — although Dr Markov is skeptical about the role of chronic viral infections in ME/CFS).

Nevertheless, Dr Markov say that by eliminating nephrodysbacteriosis, ME/CFS is usually cured. So this would appear to make nephrodysbacteriosis a key causal factor in ME/CFS.

Dr Markov says out of 2340 adult patients in his clinic with nephrodysbacteriosis and CBIS, 100% of these patients satisfied the CDC 1994 Fukuda criteria for ME/CFS. 1

The 2340 adults consisted of 1287 (55%) men and 1053 (45%) women. So there were less women than men suffering with CBIS ME/CFS, in contrast to the established fact that women get ME/CFS much more frequently than men. 1



Childhood Heavy Prolonged Antibiotic Use and Nephrodysbacteriosis

Dr Markov believes previous chronic heavy or repeated antibiotic use, especially in childhood, is a risk factor for the bacterial imbalance of nephrodysbacteriosis occuring later in life. When he examined the medical history of his CBIS ME/CFS patients, he found that 90% of patients had a history of aggressive antibiotic therapy which often began in childhood.

Interestingly, one paper found that both IBS and ME/CFS patients tend to have an history of long treatments with antibiotics as a child. The paper postulates that antibiotics promote the formation of bacterial biofilms, leading to dysbiosis. So this is in keeping with Dr Markov's observations on heavy antibiotic use being linked to nephrodysbacteriosis and ME/CFS.



Autovaccine Treatment Success Rate for CBIS ME/CFS

Dr Markov believes nephrodysbacteriosis leading to CBIS is the cause of ME/CFS, and says by treating nephrodysbacteriosis with autovaccines, 92.7% of ME/CFS patients attain a full recovery after 6 months to 2-3 years. The longer the duration of the illness, the longer it takes to cure. 1

Dr Markov finds ME/CFS patients who have their illness for more than 3 years take longer to cure. 1

Dr Markov finds the ME/CFS cure rate is 95% to 100% in patients who have had the illness for less than 5 years, but those who have had ME/CFS for more than 5 years, the cure rate is a bit less, around 90%. 1

Most ME/CFS patients with CBIS return to a normal life without relapses, and never return to the clinic, Dr Markov says. 1

Sometimes though patients who completely recovered via autovaccine treatment may get a relapse of certain symptoms after around 5 to 7 years, but this can be fixed with another autovaccine treatment. 1

Dr Markov defines recovery from ME/CFS as the cessation of all disease symptoms, as well as the disappearance of bacteria in the urine (negative urine bacterial culture), and the normalization of all urine parameters. 1

Over a 12 year period from 2009 to 2021, Dr Markov examined about 4500 child and adult patients with symptoms of ME/CFS, treated 4288 of these patients, and observed that 3975 patients out of 4288 (92.7%) achieved full recovery. 1



Detection of Nephrodysbacteriosis and CBIS

In order to detect the infections in the kidneys in the case of nephrodysbacteriosis, Dr Markov says it is necessary to use fresh warm urine directly from the bladder first thing in the morning, and the urine sample should be taken towards the end of your stream of urine (normally in urine tests you provide midstream urine, but Markov says taking a sample when you have almost emptied your bladder is better). He also says to wash the genital area around your urethra to prevent bacteria on the genital skin from contaminating the urine.

Dr Markov says that by using warm urine, you increase the sensitivity of the urine bacterial culture lab test by 2.5 to 2.7 times.

Dr Markov requires 3 urine samples taken on three consecutive days, again to increase sensitivity. If the patient is taking any antibiotic treatment, they should wait at least one month after the completion of the course of antibiotics before they provide these urine samples.

The urine sample is cultured on two different agars (agar is a bacteria growth medium), CLED agar and MacConkey agar. 1

Dr Markov's patients are provided with these two agars in the form of a urine dipslide to take home. A dipslide is just a plastic stick which contains the two agars, and which you can conveniently hold under your stream of urine. For 3 days in a row, a new dipslide should be exposed to your morning urine every day, and then left (incubated) for 24 hours to see if any bacteria grow on it, ideally at 37°C.

If you are positive for nephrodysbacteriosis, bacterial colonies will start growing on these agars within 24 hours. The dipslides are then returned to Dr Markov, who then creates an autovaccine for the patient tailor-made from these bacterial colonies. 1

Dr Markov says if there are current clinical manifestations of a urinary tract infection, then warm urine is not necessary, and a standard urine bacterial culture will be sensitive enough. 1

Note that when Dr Markov talks of nephrodysbacteriosis (kidney dysbiosis), this is not a normal infection of the kidneys or urinary tract, just as dysbiosis of the colon is not considered an infection of the intestines. Dysbiosis is where populations of harmful bacteria or fungi outgrow or are out of balance with populations of beneficial bacteria. So dysbiosis is not a raging infection, but an imbalance between good and bad micro-organisms.

So because in nephrodysbacteriosis there is no raging infection in the kidney, it is harder to detect the infection, and thus requires this more sensitive technique involving fresh warm urine, and taking three urine samples on three consecutive days.

Once an infection is detected in the kidneys by means of a urine bacterial culture, to check whether this infection is actually causing nephrodysbacteriosis and CBIS, additional lab tests are performed, including blood toxicology. Also a symptoms questionnaire must be completed by the patient in order to aid nephrodysbacteriosis and CBIS diagnosis. 1

More about the rationale behind the special urine test that Dr Markov uses in this post.

If you want to test yourself at home for kidney dysbiosis (nephrodysbacteriosis) using Dr Markov's high sensitivity urine test described here, this is quite easy: you can buy a box of CLED and MacConkey agar urine dipslides for about $25 (some dipslide suppliers listed in this post), and then follow the instructions detailed in this post.

For your home test, you can also buy some chromogenic agar plates which change color depending on the species of bacteria growing on it (see this post). In this way you can identify the bacteria in your kidney. You can buy 10 chromogenic agar plates for around $30; some suppliers listed in this post.



Chronic Bacterial Intoxication Syndrome (CBIS) Early Symptoms

In the early stage of CBIS, symptoms can include: 1
  • Prolonged sub-febrile condition (this means a mildly increased body temperature, usually considered to be less than 38.3°C).
  • Febrile attacks
  • Noticeably increased sweating, with a sharp unpleasant smell of sweat that is hard to get rid of
  • Alopecia
  • Joint lesions that mimic rheumatoid arthritis and gout
  • Isolated elevation of ESR
  • Leukopenia (decrease in white blood cells, usually neutrophils)
  • Persistent lymphocytosis (increased white blood cells) and neutropenia (low neutrophils) of unknown etiology
  • Skin lesions including urticaria, erythema, local Quincke's edema mainly on the face, atopic dermatitis, erysipelas, eczema
Dr Markov also finds urethritis, prostatitis and cystitis are often associated with nephrodysbacteriosis and CBIS. 1



The Bacterial Species Involved in Nephrodysbacteriosis

Dr Markov finds that in nephrodysbacteriosis, the bacteria typically detected in the urine are:

Bacterial Species Typically Found in the Urine of CBIS Patients:
  • Enterococcus + Escherichia coli in 93% of patients
  • Enterococcus — 37%
  • Escherichia coli — 25%
  • Staphylococcus — 10%
  • Klebsiella — 9%
  • Streptococcus — 5%
  • Enterobacter — 4%
  • Morganella — 2%
  • Acinetobacter — 1%
  • Citrobacter — 0.7%
  • Alcaligenes faecalis — 0.3%
  • Hafnia — 0.2%
  • Serratia — 0.2%

The percentages indicate the frequency that the bacterial species is found in CBIS patients. 1

Dr Markov says nephrodysbacteriosis can arise when Enterococcus or Enterobacter bacteria from the intestines translocate into the kidneys; or when Staphylococcus and Streptococcus from the nasopharynx translocate into the kidneys. 1



Analysis of the Blood of CBIS Patients for Toxic Bacterial Proteins

In Dr Igor Markov's as yet unpublished study "CBIS Report 8. Toxicological Diagnosis" (available here), he reports the results of toxicological analysis of the blood of 818 patients with CBIS and nephrodysbacteriosis. His toxicological analysis found that CBIS patients have high levels of toxic proteins originating from bacteria in their blood.

The analysis of bacterial toxins in the blood was done by means of the Toxicon diagnostic system, a lab test developed by a group of Ukrainian scientists led by pediatric toxicologist Dr Borys S Sheiman. The Toxicon lab test detects toxic proteomes of bacteria (toxicoproteomics).

According to the Toxicon test, Dr Markov found the majority of CBIS patients (81%) have severe toxemia, and 17% have moderate toxemia. Toxemia is blood poisoning from bacterial toxins.

Note that toxemia (bacterial toxins only in the blood) is not the same as septicemia (both bacteria and their toxins in the blood).


In terms of the bacterial species that these bacterial toxins originate from, the Toxicon test found that in 50% of CBIS patients, the toxins came from Enterococcus faecalis.

The frequency that other bacterial toxins were found in the blood in CBIS is shown below:

Bacterial Toxins Found in the Blood of CBIS Patients:
  • Enterococcus faecalis — in 50% of patients
  • Escherichia coli — 12%
  • Enterococcus faecalis + Escherichia coli (both together) — 27%
  • Staphylococcus aureus or Staphylococcus haemolyticus — 6%
  • Klebsiella pneumonia — 4%
  • Pseudomonas aeruginosa — 1%

Source: CBIS Report 8. Toxicological Diagnosis (available here).

The above percentages indicate the frequency that toxins from each bacterial species are found in CBIS ME/CFS patients.

The frequency that these various bacterial toxins were found in the blood in CBIS ME/CFS patients roughly corresponds to the frequency the bacteria are found in the kidneys of CBIS ME/CFS patients (see the section above for the frequency the bacteria are found in the kidneys).

So this data seems to corroborate Dr Markov's CBIS theory of ME/CFS, as not only does he find bacteria in the kidneys in CBIS patients, but he also finds high levels of toxins from those same bacteria in the blood of CBIS patients.

The Toxicon lab test found that the detoxification and elimination of toxic proteomes from the blood of CBIS patients was mainly carried out through macrophages of mesenchymal origin in 75% of patients, through the liver in 23% of patients, and via the kidneys in 2% of patients.

The table below shows the averaged results of the Toxicon blood test for adults and children with CBIS. You can see the blood levels of these cytolytic bacteria toxins is well above the norm.

Cytolytic Activity Of Toxic Proteomes (Toxicon Test).png


Source: CBIS Toxicological Diagnosis (Report 8) — that document is available here.



The Autovaccine Therapy of Nephrodysbacteriosis in ME/CFS

Dr Markov says the autovaccine treatment is safe: none of the ME/CFS patients treated had complications or negative side reactions to the autovaccine treatment. 1

(Although some people report online that autovaccines might potentially increase autoimmunity in patients who have a pre-existing autoimmune condition). 1

Autovaccine treatment follows a specific schedule:

One course of autovaccine immunization involves 10 subcutaneous autovaccine injections, with one injection given every other day, in increasing doses, over a period of 20 days. After each course of injections, there is a rest period of 3 to 4 weeks, where patients do not receive any injections.

One cycle of the autovaccine treatment involves 2 or 3 courses of immunization. So one whole treatment cycle lasts for about 70 to 110 days. 1

After one treatment cycle, there is a rest of 3 to 4 months, before the next cycle begins.

ME/CFS patients who have had their illness for more than 3 years tend to require more treatment cycles in order to be cured (2 to 3 years treatment). Patients who have had their illness for less than 3 years may be cured after only one treatment cycle (6 months treatment). 1

But positive changes in health begin during the first course of vaccination. There are often ups and downs in health level during treatment, but the overall health direction is upwards.

The autovaccine injections are administered on an outpatient basis at the patient's home (the patient takes home the autovaccines, and injects them himself), or patients may attend the clinic for the vaccinations. The autovaccine treatment protocol is customized for the individual patient.

Dr Markov says he treats ME/CFS patients from mild to severe. 1 But elsewhere he says he does not know if his autovaccine protocol will be effective for bedridden (severe) patients. 1



Cost of the Treatment

The cost of autovaccine treatment is very approximately $500 for six month's worth of vaccines (one treatment cycle). The cost it depends on the number of vaccines Dr Markov prescribes, as each patient is given their own treatment plan based on the bacteria found in their urine culture. Every six months a new set of vaccines will needed if the patient wants to continue treatment.

Dr Markov finds most ME/CFS patients will require 2 to 3 years of autovaccine treatment to be cured, so the total costs will be around $2000 to $3000 for the vaccines. However, for patients who have had ME/CFS for less than 3 years, one treatment cycle (6 months) may be enough, and so the total costs will be much lower.

In addition to the vaccine costs, a consultation with Dr Markov is required. The cost of a remote consultation by video conference is $300, and the cost of a remote email consultation is $200.

So the outlay for the first 6 months of treatment is approximately $700 with an email consultation. After the first six months of treatment, ME/CFS patients should already be noticing improvements, and can then decide whether they want to continue with the autovaccine therapy.



Reviews of Dr Markov and His Clinics

After an extensive Google search in the English, Ukrainian and Russian languages, no online accounts could be found of any ME/CFS patient who was cured by Dr Markov's autovaccine treatment. But equally, no accounts could be found of ME/CFS patients who have received Dr Markov's autovaccine treatment, and had failed to improve.

However, several patient reviews of Dr Markov's autovaccine therapy for other conditions were uncovered, such as the reviews listed in this post. Other reviews in this post and this.

The reviews are mixed and polarized: many reviews criticize Dr Markov and his clinic; other reviews sing his praises and claim Dr Markov has cured their illnesses. Generally in these reviews, if the autovaccine helped the patient's disease or condition, then they praise Dr Markov; but if it did not help, and therefore they feel their money was wasted, then they criticize.

Looking back at an autovaccine study from the 1930s, it was observed back then that autovaccines can often work well, but also can often fail to have any effect. So with autovaccine treatments for infections, it seems that sometimes they work, and sometimes they do not. So this fact could explain the polarized reviews.

In the case of treating ME/CFS, though, autovaccine therapy works most of the time, according to Dr Markov, who reports a 93% cure rate.



Future Treatment Developments From Dr Markov: PrimaVac Vaccines

Dr Markov has created nine off-the-shelf PrimaVac™ vaccines to treat kidney dysbiosis and CBIS. These vaccines target many of the common bacterial species found in nephrodysbacteriosis.

Markov's PrimaVac vaccines are "one size fits all" products which target common bacterial species that cause urinary tract infections. These off-the-shelf vaccines make it easier to treat CBIS ME/CFS patients, because these ready-made vaccines can often be used instead of having to create personalized autovaccines.

Dr Markov says the effectiveness of "one size fits all" vaccines is no less than the efficacy of his autovaccines, and sometimes they work even better than autovaccines, due to the wider spectrum of bacterial antigens in the vaccine. Dr Markov uses the PrimaVac series of vaccines he developed to treat CBIS patients at his clinic.

The Markov Clinic's PrimaVac series of vaccines include:

Eco-PrimaVac — contains antigens from Escherichia coli, Enterococcus faecalis, Enterococcus faecium and Enterococcus durans. Patent application is here.

Staphylo-PrimaVac — contains antigens from Staphylococcus aureus, Staphylococcus haemolyticus and Staphylococcus epidermidis. Patent application is here.

Dr Markov's other vaccine patents here.

These "one size fits all" vaccines however would need to go through clinical trials before being marketed internationally, so that is something which the clinic would like to do in future. By contrast, physicians are free to create autovaccines from a patient's own bacteria without needing any clinical trial or license. 1



How Dr Markov Is Informing the ME/CFS Community of the CBIS Theory

In the last few months, Dr Markov has informed the following organizations about his CBIS Theory of ME/CFS and autovaccine treatment:
  • ME Association (UK)
  • Action for ME
  • Solve for ME/CFS
  • ME Vereniging (Netherlands)
  • CDC and National Institutes of Health (USA)
He also participated in chat on #MillionsMissing on annual ME/CFS day, and the 1st European Myalgic Encephalomyelitis Alliance (EMEA) / European Federation of Neurological Associations (EFNA) roundtable meeting. 1

The CDC placed Dr Markov's comments on the Systematic Review Report for ME/CFS. 1
 
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hb8847

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Incredible effort @Hip , amazing to have all the essential info summarised in one place. And referenced too! Fantastic work as per.

Before the antibiotics era, autovaccines were utilized to treat infections in humans; but these days autovaccines are mostly employed for infections of livestock.

Why is this the case again, is it because autovaccines take longer to have an effect? It's surprising to me they are not more widely used as they would seem to be a lot more targeted than antibiotics, which just nuke everything in sight and clearly can do quite a lot of damage to one's internal microbiome (and first line of immune defence).

And do you know if they are used in animals in the same way, as in, are they produced from the animals urine on an individual basis or is there a mass produced autovaccine that covers the usual culprits of bacteria? Writing that out it seems obvious to me it would be the latter, surely there's no way they would spend on creating individual autovaccines for animals.

And what are they given to animals for, is it to cure from certain illnesses or are they a preventative against illness?

Furthermore, blood passing through the intestines is filtered by the first-pass metabolism in the liver, which removes 95% to 99% of any LPS. But blood going through the kidneys is not routed through the first-pass metabolism, so is not filtered of its LPS.

Am I right in thinking then that endotoxins released from intestinal dysbiosis are unlikely to directly cause illness, as the vast majority will be filtered out by the liver? And is this an accepted fact?

If so, why are we seeing positive results from things like fecal transplants and interventions to address leaky gut and gut dysbiosis, is the idea these are having an indirect affect on CFS through a weakening of the immune system?

Once an infection is detected in the kidneys by means of a urine bacterial culture, to check whether this infection is actually causing nephrodysbacteriosis and CBIS, additional lab tests are performed, including blood toxicology.

Then why not go straight to the blood toxicology, if you need that to confirm CBIS? Or is the urine test performed to determine which are the offending bacteria, if any? @Hipsman have you had the blood work done too?


So because in nephrodysbacteriosis there is no raging infection in the kidney, it is harder to detect the infection, and thus requires special more sensitive techniques such as using warm urine, and taking three urine samples on three consecutive days.

If it requires such sensitive techniques to pick up evidence of bacteria in the urine, I'm wondering whether some might be missed in the process. For example @Hipsman relayed that Dr Markov once had to do 15 tests to find evidence of bacteria, but then maybe if he only performs one test he'd miss a bunch of other bacteria? Or perhaps the 7% of healthy subjects to have CBIS would be considerably higher were Markov to perform multiple tests on them too...
 

perrier

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This says it all.

Hip, I admire your thoroughness, but I don't understand why we need another thread on this.
It is a good idea. Hip has done a superb job of summarising the material. People are going to Ukraine, and Dr. Markov is trying to contact researchers in the West. If this is just a "gros ballon" or as pronounced here in Quebec Grosse Ballooon---it will Peter out soon. But at the moment there is some momentum to look at this work.
 

Hip

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This says it all.

Hip, I admire your thoroughness, but I don't understand why we need another thread on this.
I agree, you'd think there would be at least a few stories from Ukrainian ME/CFS patients who had recovered via Dr Markov's autovaccine therapy.

The reason for this thread is just to place the info into one article, so that people can get a rapid overview of the CBIS theory of ME/CFS. People seemed to be asking the same questions to Dr Markov that he'd already answered, so there was a need for a reasonably concise summary.

I am also one of these people who tends to absorb information better when I make my own notes, so the above is just my own attempt to understand Dr Markov's ideas.



Irrespective of the treatment efficacy of autovaccines, I've found Dr Markov's theory that bacterial toxins are a key player in ME/CFS etiology food for thought. This is not the first time such theories have been proposed.

Dr David S. Bell for example proposed that ME/CFS may be a form of slow sepsis, and the Markov CBIS theory would certainly fit into that description.

Sepsis often involves bacteria in the blood (septicemia), which we do not see in ME/CFS. However, it may be that the presence of bacterial toxins in the blood, leaking out from the kidneys, is enough to trigger a sepsis-like state.

Remember that sepsis is an exaggerated, dysregulated inflammatory immune response caused an infection; but it's not the pathogens themselves which cause sepsis, but the toxins these pathogens secrete.

For example, sepsis caused by gram negative bacteria is thought to be largely caused by the bacterial toxin LPS secreted by the bacteria. And sepsis caused by gram positive bacteria may result from lipoteichoic acid, which is the gram positive bacteria's equivalent to LPS.

Sepsis causes major energy metabolism down-regulation and mitochondrial changes, which are consistent with those seen in ME/CFS. Specifically, sepsis promotes an increase in pyruvate dehydrogenase kinase, which in turn reduces inhibits pyruvate dehydrogenase, a crucial enzyme in aerobic glycolysis (pyruvate dehydrogenase kinase acts as an inhibitor of pyruvate dehydrogenase). Ref: here.

Fluge and Mella of course found an increased expression of pyruvate dehydrogenase kinases in ME/CFS patients, which they think might explain the low energy state of ME/CFS.



At the moment I am interested in looking into how bacterial toxins in the bloodstream might lead to the various known pathophysiological features of ME/CFS.

ME/CFS involves many pathophysiological characteristics, including apparent energy metabolism dysfunctions and chronic low-level viral infections of the tissues. I have been looking at whether the CBIS theory of ME/CFS might explain these pathophysiological features.

I found that several pathophysiological characteristics could be explained by the Markov CBIS theory of ME/CFS, which are as follows:

Energy Metabolism Dysfunction. Fluge and Mella found when healthy cells in vitro are exposed to the serum of ME/CFS patients, the cells develop energy metabolism alterations, including excessive lactate secretion. Could the bacterial toxins entering the bloodstream from the kidneys explain these energy metabolism dysfunctions?

Well LPS seems to cause energy metabolism changes, as this study found that mice exposed to LPS entered into a hypometabolic state. This occurs to conserve energy, so that the immune system has sufficient energy to fight the infection (the presence of LPS usually signifies a bacterial infection).

And one study found that TLR4 activation from LPS resulted in a re-programming of the energy metabolism, shifting energy production away from oxidative phosphorylation, and towards to glycolysis. The LPS exposure also caused mitochondrial fragmentation.

Mitochondrial Fission. Dr Bhupesh Prusty found that when blood serum from ME/CFS patients is added to a cell line, the mitochondria in the cells become fragmented, indicating that there is something in ME/CFS serum which causes mitochondrial fragmentation. Well, the study mentioned just above found that mitochondria exposed to LPS became fragmented. See also: "there's something in the serum of ME/CFS patients".

Autoimmune Connection to ME/CFS. Could LPS or other bacterial toxins leaking into the bloodstream help explain the fact that ME/CFS patients often have comorbid autoimmune diseases (POTS for example may be autoimmune)? Well this review paper indicates that TLR2 and TLR4 play an essential role in the development of autoimmune diseases. LPS is an agonist of TLR4 (the main function of TLR4 is to detect LPS from bacterial infections). And as mentioned earlier, enterotoxin B from Staphylococcus may also play a critical role in the pathogenesis of autoimmune disorders.

Brain Inflammation and Microglia Activation. Studies have shown ME/CFS patients have low-grade neuroinflammation and microglial activation. Could bacterial toxins in part be the cause? Well, one study found that adding high levels of LPS to the blood of rodents induces microglial activation. LPS causes this inflammation by activating TLR4.

The Viral Connection. Dr Markov himself does not appear to be a subscriber to the idea that ongoing chronic viral infections play a role in ME/CFS. However, the viral theory and Dr Markov's CBIS theory may be compatible if we examine ME/CFS from the perspective of immune priming.

Immune priming is where the immune system becomes hypersensitized to infection, and thus responds too fiercely to infection. This hypersensitivity occurs when the immune system has been previously exposed to an inflammatory factor, such as LPS or interferon gamma. Thus if we have LPS constantly entering the blood from the kidneys, this could prime the immune system into a hypersensitive state. Then when the immune system meets the chronic viral infections found in ME/CFS, it may be activated too strongly, leading to ME/CFS symptoms.

On a different angle, it's also interesting how viruses linked to ME/CFS like coxsackievirus B are able to chronically infect the kidneys, and thus may be able to set the stage for a bacterial kidney dysbiosis. Epstein-Barr virus is also able to chronically infect the kidneys. See also here.

Impaired Viral Clearance. In ME/CFS it seems that patients are not able to fully clear viral infection from their tissues. Could bacterial toxins help explain why this is? Well one study found that repeated exposure of LPS caused endotoxin tolerance, where microglia in the brain shift towards an M2 phenotype, which is not capable of fighting pathogens (M1 microglia fight pathogens, whereas M2 microglia promote brain repair). A study found endotoxin tolerance also results in macrophages shifting to the M2 phenotype.

Viral Mucous Membrane Connection. The viruses commonly linked to ME/CFS all have the ability to infect mucous membranes, so it could be that such viral infection sets up the dysfunction of mucosal immunity Dr Markov believes is the basis of ME/CFS.

Mucosal Immunity. Dr Oleg Markov says bacterial dysbiosis in the kidneys is due to dysfunction in mucosal immunity. The mucous membranes include mouth, gums, throat, nose, sinuses, stomach, intestines, and in the kidneys too. The idea of defective mucosal immunity perhaps ties up with some of the phenomena we see in ME/CFS, like the chronic sore throat, the chronic nasal or sinus inflammation, dysbiosis in the colon, and SIBO in the small intestine. That all looks like ME/CFS patients are having trouble controlling mucosal pathogens.

The Swollen Lymph Nodes of ME/CFS. Dr Markov says the kidney dysbiosis infections of ME/CFS involve a dysfunction of mucosal immunity. Well the lymph nodes, spleen and mucosa-associated lymphatic tissue (MALT) form part of mucosal immunity, and lymph nodes are swollen in ME/CFS.

IDO2 Enzyme and Metabolic Trap. Mutations in the IDO2 gene which reduce the effectiveness of this enzyme are more frequently found in ME/CFS patients than the general population. Dr Robert Phair has hypothesized a metabolic trap theory to explain this empirical observation of the IDO2 mutations.

However, as an alternative (or a parallel) theory to the metabolic trap hypothesis, an LPS etiology of ME/CFS might also explain this empirical observation: this study found IDO2 knock-out mice had increased production of inflammatory cytokines when exposed to LPS, so this suggests people who have these IDO2 mutations will be more susceptible to the pro-inflammatory effects of LPS in the bloodstream.

Prof Michael Maes says that in ME/CFS "chronic or intermittent translocation of LPS into the systemic circulation can induce a state of tolerance and alternative activation in macrophages and monocytes characteristic of endotoxin tolerance via the activation of IDO, kynurenine and the AhR [aryl hydrocarbon receptor]".



It is also instructive to compare Dr Markov's CBIS Theory of ME/CFS to related theories:

Prof Michael Maes's LPS Leaky Gut Theory of ME/CFS. The leaky gut theory of ME/CFS from Prof Michael Maes proposes LPS from bacteria on the intestinal mucous membranes are constantly secreting LPS into the blood, because some ME/CFS patients have leaky gut (intestinal hyperpermeability) which allows the LPS to escape the intestines and enter the bloodstream.

Prof Maes reported some anecdotal success in treating ME/CFS using supplements and diet to help repair leaky gut. We have also seen anecdotal reports of ME/CFS symptoms improving when patients address their SIBO infections.

Prof Gottfries's Staphylococcus Vaccine Therapy. Professor Carl-Gerhard Gottfries's published a clinical study in 2002 demonstrating that a Staphylococcus vaccine was an effective treatment for ME/CFS. The study found that 33% of ME/CFS patients obtained a 50% reduction in symptoms from the Staphylococcus vaccine.

Staphylococcus is one of the bacteria that Dr Markov finds in the urine when he tests ME/CFS patients for nephrodysbacteriosis kidney infections; and he finds Staphylococcus in the nasopharynx area too.
 
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WantedAlive

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Dr David S. Bell for example proposed that ME/CFS may be a form of slow sepsis. Sepsis involves bacteria in the blood (septicemia)
Respectfully, this is a common misunderstanding, sepsis is not septicemia. Septicemia is a blood infection, that is correct. However sepsis is differently defined as a systemic dysregulated immune response to an infection. Sepsis and SIRS (systemic inflammatory response syndrome) are both the same with the exception that sepsis is secondary to a bacterial infection, SIRS is secondary to a non-bacterial infection. With sepsis, it is the dysregulated immune response that is the danger, the pathogen becomes somewhat an innocent bystander.

I've always liked Bell's explanation, ME/CFS looks very much like a chronic smoldering sepsis. And metabolically ME/CFS has been matched to SIRS, 'exactly' I think was the quote. If I recall two researchers were in agreement on this. But certainly as you say its not septicemia, that's blood poisoning.

Nice job putting all this together @Hip , it will be very much appreciated by the community.
 

5vforest

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The reason for this thread is just to place the info into one article, so that people can get a rapid overview of the CBIS theory of ME/CFS. People seemed to be asking the same questions to Dr Markov that he'd already answered, so there was a need for a reasonably concise summary
I agree, I think this is a great article -- I just don't like it when topics get spread across multiple threads, but that can be my problem :)
 

Hip

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sepsis is not septicemia
Yes, sepsis is the exaggerated, dysregulated inflammatory immune response that can be caused by septicemia.

In this post there are some definitions:
Some Notes on Terminology

Bacteremia = the presence of bacteria in the bloodstream (which can temporarily occur in a non-dangerous way when you brush your teeth).

Septicemia = the presence and multiplication of bacteria in the blood (which is more dangerous than bacteremia). Septicemia is also known as blood poisoning.

Systemic inflammatory response syndrome (SIRS) = a dysregulated inflammatory state affecting the whole body, usually (but not always) in response to infection. SIRS is a type of cytokine storm, in which there is abnormal regulation of cytokines.

Sepsis = SIRS caused by septicemia or by another infection in the body, resulting in injury to body tissues and organs. Usually the infection is bacterial, but it may also be fungal, viral or parasitic.

Septic shock = the dangerously low blood pressure that can occur during sepsis.
 

Hip

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@hb8847 I don't really know any precise answers to your above questions, as I am still learning all about this myself. But Google is your friend if you are looking for answers!
 

Hipsman

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Then why not go straight to the blood toxicology, if you need that to confirm CBIS? Or is the urine test performed to determine which are the offending bacteria, if any? @Hipsman have you had the blood work done too?
Reason is simple: cost. Dr. Igor Markov ordered blood toxycology for me before I started the treatment when he read that people wanted confirmation that there was a problem in the first place. He said that he doesn’t do such tests normally, because they just add in cost. In Ukraine an avarage person would find his treatment on the expensive side already, so saving cost is necessary I guess.
 
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Where are all those thousands cured ME patients?

Why have we not heard from a vast amount of them?

And why don't we see this man on any of the international ME conferences?
If what he has found in his research is so amazing, he should be there.

When something seems to be good to be true, it makes me wonder if it really is too good to be true.
 
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What I found is that

“Additionally, we revealed that SPEA (Streptococcal Pyrogenic Exotoxin A) triggers immunosuppressive programs in monocytes that facilitate the accumulation of regulatory T cells (Tregs) in in vitro monocyte/CD4+ T-cell cocultures. Immunosuppressive factors include anti-inflammatory interleukin 10 (IL-10), co-inhibitory surface molecule programmed cell death 1 ligand 1 (PD-L1), and the inhibitory indoleamine 2,3-dioxygenase (IDO)/kynurenine effector system”

https://pubmed.ncbi.nlm.nih.gov/31412561/
 

Celandine

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Very interesting. Russian medicine is definitely worth a look. Because they don't have the situation where their whole medical system is slave to insurance companies and drug companies, like many Western countries, they often use things that don't take hold in the West. Phage therapy for bacterial infections, for instance, is very successfully used over there as an alternative to antibiotics. Very personalised medicine in that case ,as blood is tested and the specific phage for your condition can be prescribed. Phages can't be patented, so, of course, drug companies (working hand in hand with insurers) aren't interested in pushing this. Autovaccines would likely be a similar situation. They also use hyperbaric oxygen therapy for many illnesses over there while in the US it is only licensed for very very limited situations. Again, that'll be because they'd rather sell expensive drugs than offer unpatentable oxygen therapy.
 

sb4

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Nice work once again @Hip!

My onset was from tonsilitis like illness. Perhaps Staphylococcus or Streptococcus got into the nasopharynx and traveled down to my kidneys? Interestingly I saw an infectious disease specialist a couple years ago who ruled out a couple of infections, when I looked at the results myself, the one thing that did come back over range I think was either Staph or Strep. When I asked them about it they said it was only slightly over range and it wasn't a concern.

I got a urinary track infection (I'm pretty sure, but didn't go to the docs) a couple years ago from peeing in a bottle beside my bed (TMI?). In that time I felt like I needed to pee constantly even though my bladder was empty yet I noticed no change in other symptoms.

Hip, where you get your reoccurring UTI do you notice symptom change?
 

hb8847

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@hb8847 I don't really know any precise answers to your above questions, as I am still learning all about this myself. But Google is your friend if you are looking for answers!
Sorry yes I wasn't intending them as questions directed to you, God knows you've done enough work on the matter. I was more just verbalising my thought process while reading your article, and using it as a jump off point for my own research. Thanks again.
 
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Aidan Walsh

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Where are all those thousands cured ME patients?

Why have we not heard from a vast amount of them?

And why don't we see this man on any of the international ME conferences?
If what he has found in his research is so amazing, he should be there.

When something seems to be good to be true, it makes me wonder if it really is too good to be true.
How many of these patients were tested for the 7 types of porphyrias in blood stool urine or genetics?
 

Daffodil

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i hope i dont sound like too much of a dummy but my brain fog is so bad, i cannot read enough of this thread. i just have one question if someone might answer in layman's terms. i understand the disease symptoms are caused by chronic smouldering bacterial infection. i agree with that. but why does this doctor think it is in the kidneys? is it because he found it in the urine? why does he think it is not centred in the gut? did he test feces?

thank you
 

hb8847

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i hope i dont sound like too much of a dummy but my brain fog is so bad, i cannot read enough of this thread. i just have one question if someone might answer in layman's terms. i understand the disease symptoms are caused by chronic smouldering bacterial infection. i agree with that. but why does this doctor think it is in the kidneys? is it because he found it in the urine? why does he think it is not centred in the gut? did he test feces?

thank you

My understanding (and please @Hip correct me if I'm wrong) is that Markov bases his theory of CBIS on:

- The existence of a microbiome in the kidneys/urinary tract (referenced above)

- The fact that the kidneys process considerably more blood than that which passes through the intestines, so any endotoxins produced by bacteria in the kidneys is far more likely to seep into the blood

- The fact that all blood from the intestines goes first to the liver for processing, and the liver would remove 95% or more of the endotoxins present. This doesn't happen with blood from the kidneys

- I understand though he hasn't performed biopsies of the kidneys to confirm his diagnosis and his prognosis is theoretical

- He diagnoses this through testing the urine, and follows that up by testing the blood for endotoxins. Again I don't know whether this method would be exclusionary of intestinal dysbiosis, I see no reason why some intestinal endotoxins wouldn't be able to make their way to the urine

- His idea is that overuse of antibiotics, particularly in childhood, is a contributing factor to CBIS

- He posits that bacterial infections acquired elsewhere, including in the throat and in intestinal dysbiosis, can eventually lead to the CBIS of the kidneys.

- You ask about whether he tests the faeces; I assume from what he says, existence of the same problematic bacteria in the stool as is present in the urine wouldn't exclude CBIS because it's very possible the same bacteria could be found in both places, and indeed could have "infected" the kidney microbiome via the gut.