Chronic bronchitis - Symbioflor®

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Symbioflor, which is used to treat chronic bronchitis, among other things, is available in three variants. In principle, it has been on the market for over 70 years and contains - in the „immune“ variant Enterococcus faecalis DSM 16440- and E.coli DSM 17252-bacteria and zinc.

Anyone suffering from a grass pollen allergy and chronic bronchitis is plagued by a permanent, untreatable chesty cough as soon as they „move“ during the winter months. Only outside, in the cold, is there peace and quiet.

Visits to the doctor, even to supposedly renowned lung specialists (pulmonologists), do not result in a therapy suggestion, not even a target-oriented diagnosis, because diagnostically all parameters are without findings, normal - everything is in perfect order, - apart from the still unchanged and truly plaguing irritating cough, possibly to the point of vomiting.

The fact that Symbioflor is effective against this irritating cough is not because E. faecalis It is not only because of its positive, strengthening influence on the immune system in the intestine (GALT - Gut-Associated Lymphoid Tissue).

However E. faecalis properties that can be both good and „bad“, depending on the state of the intestinal immune system. It is a quick-change artist that plays mimicry with the immune system.

Jekyll & Hyde

Dr. Jekyll, the reliable doctor E. faecalis in the intestine.

Since day one, literally from birth, it has been doing exemplary work: producing vitamins, regulating the pH value, chasing away nasty bacteria. An obvious man of honor.
But it hides its virulent factors like a respectable teacher's café hides its coffee cup. It carries the right antigens and tricks the immune system into ignoring it.

But then something happens that actually seemed unthinkable in this story: an antibiotic, an injury, an immune deficiency, and suddenly our good intestinal friend turns into the mean Mr. Hyde.

And Mr. Hyde has plans. Evil plans. He leaves the safe realm of the intestines and wanders straight into the bloodstream without any invitation.
There it builds a „biofilm“ fortress that gives antibiotics bloody noses and grits their teeth. It hides in macrophages like a goblin in the forest and deceives the immune system with proteins that look like tickets to a VIP party.

Endocarditis? Masterpiece. Urinary tract infections? Routine. Peritoneal infections? Hobby. In hospitals, Mr. Hyde is now the star attraction: he causes 11% of all nosocomial infections.

The boundary between Jekyll and Hyde is intangible. Mr. Hyde is always in Dr. Jekyll's body. A broad-spectrum antibiotic, an immune system that has not healed completely, and Dr. Jekyll drinks the wrong elixir and - transforms. The plasticity of this bacterium is unparalleled: it snatches up any antibiotic resistance gene with the speed of a pickpocket.

There is no cure, no serum that can reverse the transformation. One can only hope that Dr. Jekyll remains in a healthy gut and does not mutate into Mr. Hyde ...

What's behind it?

How Agnieszka Daca and Tomasz Jarzembowski in her article of 2024 Feb 19 in the International journal of molecular sciences „From the Friend to the Foe- Enterococcus faecalis Diverse Impact on the Human Immune System“, is E. faecalis a double-edged sword.

The EFSA (European Food Safety Authority), similar to the FDA's GRAS (Generally Recognized as Safe) list, lists food additives, food contact materials, microorganisms and other substances whose safety has been scientifically evaluated and approved.

Symbioflor^® was not approved - although it contains the „safer“ strain DSM 16440.

The problem is that there is no known dosage at which the desired effect is achieved, nor at what point E. faecalis „is “too much" and translocation is imminent, Enterococcus faecalis passes through the intestinal wall and enters compartments such as the bloodstream or peritoneal cavity, where it develops its pathogenic effect.

So whether it looks good or bad depends on the context:

In a healthy gut a hero, after overconsumption of antibiotics an opportunist, in a wound or on the heart a killer and In the hospital environment a serial killer.

The above-mentioned article describes, among other things, the case of a Dysbiosis (when the microbiome gets out of balance):

A key element that E. faecalis controlled in a healthy state, is Deoxycholate (DCA). DCA sensitizes E. faecalis and controls its replicative and transcriptional activity.
This means: Even with the same quantity E. faecalis, when the deoxycholate regulation is gone (e.g. after antibiotics), its effect turns negative.

The Absolute number is less important than the balance of the system.

Pro & contra E. faecalis

Pro ...

• E. faecalis produces vitamins, metabolizes nutrients and maintains the intestinal pH value. That is essential.

• The immune system needs training
  MALT (mucus-associated lymphoid tissue) only reaches its full functional and structural capacity through contact with commensal bacteria. E. faecalis is the primary „trainer“.

• It protects against invasion
  E. faecalis and other commensal microorganisms prevent pathogenic bacteria by competing for space and nutrients and by producing bacteriocins.

• It heals inflammation
  The Symbioflor example shows that the recurrence rate in chronic bronchitis was reduced by 43% during supplementation and by 68% 8 months later.

... contra

• It's a hidden killer
  E. faecalis can cause endocarditis, urogenital infections, intraperitoneal infections and sepsis. Approximately 10-20% of community-acquired endocarditis is caused by E. faecalis.

• It's everywhere in the hospital
  E. faecalis is responsible for at least 11% of all nosocomial infections (HAI - Hospital-Acquired Infection), i.e. hospital-acquired infections, with increasing morbidity and mortality.

• It is disproportionately difficult to treat
  E. faecalis has the ability to form biofilms, a structure of polysaccharides, proteins and lipids that is practically impenetrable to antibiotics and immune cells.

• It hides from the immune system better than any spy
  The article shows: It produces ROS to survive, hides in macrophages, uses Tax (enterococcal aggregation substance) to activate T cells and thus deceive them again.

But not E. faecalis itself is the problem, but often (e.g. before operations) broad-spectrum antibiotics that weaken the immune system.
The pathogenic properties are acquired through the horizontal transfer of pathogenicity and antibiotic resistance-associated genetic elements. This is comparable to when bandits do not build weapons themselves, but borrow an entire arsenal from others.

The mechanism in detail

1. plasmids - the means of transportation

Plasmid-mediated genes in enterococci are thought to have contributed to the development of vancomycin-resistant enterococci (VRE), particularly important in medical environments such as clinics, doctors' surgeries, etc.).

Plasmids are small, circular pieces of DNA that can be passed between bacteria or like USB sticks on which „antibiotic resistance“ is stored. E. faecalis takes a USB stick and copies the genes onto it.

2. horizontal gene transfer - active predation

This is not only passive, E. faecalis can also be active:

• take up plasmids from other bacteria (transformation)
• Absorb DNA fragments from dead bacteria
• Make direct contact with other bacteria and exchange genes (Conjugation)

... is like gene theft in the gut.

Selection through antibiotics

This is the natural selection in quick succession:

Scenario without antibiotics:

• There are 100 different strains of E. faecalis in your gut
• 99 are sensitive, 1 is randomly resistant
• The resistant strain has no advantage (no antibiotic on site)
• All 100 survive equally well
• The resistant strain remains at 1%

Scenario WITH antibiotics:

• There are 100 different strains of E. faecalis
• 99 are sensitive, 1 resistant
• Antibiotics are administered and the 99 die immediately
• The resistant strain takes over the whole party ...
• After antibiotic administration, 95% of the population are resistant

... and that in a few days stat years: a selection explosion!

VRE (Vancomycin-Resistant Enterococci)

as an example from the above article:

Vancomycin-resistant enterococci (VRE) are partly caused by plasmid-mediated genes.

Why is this a de facto horror scenario?

Because Vancomycin the Antibiotic of last resort represents. If the pathogen is resistant to all other antibiotics, the only remaining clinical options are Vancomycin. But if the pathogen itself is resistant to it, then this is a problem that cannot be solved by conventional medicine ...
The only effective option is the use of essential oils, which have a bactericidal and virucidal effect and to which no pathogen can become resistant because they represent hundreds of different „antibiotics“ to which the pathogen is exposed. So even E. faecalis strike sail.

... and why is Symbioflor^® then sold?

It is valid enough to be „tried and tested“, but not transparent enough to be considered modern.

Or because it is a „safe“ strain and - it works. How long remains to be seen. For example, the EF-2001 strain (a probiotic strain) contains relatively few antibiotic resistance genes - but the ones it does have are associated with natural Enterococcus resistance to certain antibiotics.

The sequencing data for the Symbioflor 1 strain has not been made publicly available, so it is not possible to verify the exact composition, although the manufacturer states on its website „As a drug, Enterococcus faecalis DSM 16440 has been very well studied for decades and its genes have been fully sequenced.„

I asked the manufacturer for the complete genome sequence of Enterococcus faecalis DSM 16440 requested. I will update accordingly.

That means: Even the „safe“ probiotic strains can transfer their natural resistance genes to wild E. faecalis in the gut. pass on.

This is precisely why the article states that E. faecalis is believed to be one of the most widespread multidrug-resistant hospital pathogens worldwide.

This means that there are already tribes that have been

• Ampicillin
• Erythromycin
• Fluoroquinolones
• Gentamycin
• Vancomycin
• possibly several of them combined

are resistant.

E. faecalis has natural Resistance to:

• Trimethoprim
• Lincosamides (e.g. clindamycin)

That is intrinsic, not acquired.

(For more information on the state of research in 2010, see here available in full text).

Risk factors

• Antibiotic (over)consumption causes dysbiosis
• Disorders of the intestinal barrier, e.g. due to intestinal surgery, inflammatory bowel disease (IBD, Crohn's disease) and intensive care measures (e.g. gastric tube, catheter)

If the intestine is „injured“ and E. faecalis resides in the intestine, the risk of translocation increases.

What are the warning signs?

When Mr. Hyde appears on the scene, this usually happens primarily through

Urinary tract infections (UTI).

UTIs through E. faecalis are most often acute and diagnosis is easy due to the rapid onset of specific symptoms:

• Burning sensation when urinating
• More frequent urination (pollakiuria)
• Cloudy and / or bloody urine
• Pain in the lower abdomen and / or pelvic area

DangerWith immunocompromised patients (e.g. after transplantation) the symptoms are much more subtle or not present at all, the muted immune response associated with rather non-specific (or even absent) symptoms.
Here needs special attention!

Intra-abdominal infections (peritonitis/abscesses)

when the pathogen enters the abdominal cavity. Approximately 25% of infections in intensive care units (ICUs) are caused by E. faecalis caused.

Practical symptoms:

• Severe abdominal pain
• Fever - often high >38.5°C
• Nausea / vomiting
• Signs of peritonitis (classic: guarding - the muscles tense up immediately when pressure is applied to the abdomen, rebound tenderness - extreme pain when the pressure is suddenly released)

The problem: These symptoms are not generally specific to E. faecalis, but has just been

• an abdominal operation
• Liver transplantation

and then develop into

• Fever
• Abdominal pain

this is known as RED FLAG for E. faecalis to interpret!

Endocarditis

when the heart muscle is affected. It is assumed that E. faecalis is now responsible for 10-20% of endocarditis cases acquired outside the hospital environment.

Practical symptoms (classic):

• Persistent fever (days/weeks)
• Dizziness, weakness, tiredness
• New or worsening pathological Heart murmur
• Petechiae (small red dots on the skin - bleeding)
• Osler node (painful nodules on fingertips/toes)
• Janeway lesions (indolent red spots on palms of hands/soles of feet)
• Splinter hemorrhages (small bleedings under the nails)

Endocarditis due to E. faecalis can silent i.e. none of the above symptoms occur.

Sepsis - Emergency scenarios!

in the case of systemic pathogen infestation, i.e. the entire organism is affected.

Practical symptoms (SIRS criteria - Systemic Inflammatory Response Syndrome):

• Fever >38°C or hypothermia <36°C
• Heart rate >90/min
• Respiratory rate >20/min or pCO2 <32 mmHg
• Leukocytes (white blood cells) >12.000 or <4.000

For septic shock

• Drop in blood pressure (cannot be remedied with fluids)
• Organ failure (kidneys, liver, lungs)
• Change of consciousness
• Tachycardia, sweating

Are there no alternatives?

Jain - although there is a research team around María C. Urdaci, Laboratoire de Microbiologie et Biochimie Appliquée (LBMA), Université de Bordeaux, France, which deals with E. durans EP1 deals with:

The strain E. durans EP1 fulfills the requirements set by EFSA. E. durans EP1 showed anti-inflammatory properties, increased IgA cells in the mesenteric lymph nodes after 7 days and modulated the microbiome by increasing Faecalibacterium prausnitzii. In addition, no adverse effects were observed in mice receiving EP1 for 21 days, as in this comparative study Comparative genomic analysis for the presence of potential enterococcal virulence factors in the probiotic Enterococcus faecalis strain Symbioflor 1 occupied.

E. duran's OSY-EGY has no plasmids that can contain „bad“ code like a Trojan horse (see USB stick above), nor can it harbor any, and its genome contains one confirmed and three potential CRISPR arrays that confer sequence-based immunity to phage modification and horizontal gene transfer.

Despite all the proven - especially safety-related - advantages, no commercial product is available.