A Simplified Model of Psoriasis Pathogenesis
A few words about the model of psoriasis pathogenesis. According to this model, psoriasis is a consequence of increased kPAMP levels (specific bacterial products) in blood flow. Two main factors for the increased kPAMP levels in blood flow:
SP1. Small intestinal hyperpermeability for bacterial products with PAMP .
SP2. Small intestinal bacterial overgrowth (SIBO) with PsB-bacteria and EnB-bacteria.
Factor SP1 determines the amount of bacterial products that can penetrate into blood through small intestinal wall (conventionally, every minute through every cm2).
Factor SP2 determines the quantity and range of bacterial products constantly formed in parietal biofilm of small intestine (conventionally, every minute on every cm2).
The Role of Psoriagenic Bacteria (PsB) and Enhancing bacteria (EnB)
Composition of small intestinal parietal microbiome determines the range of bacterial products formed.
Also among the bacteria that inhabit the small intestine are PsB (psoragenic) and EnB (enhancing).
The peptidoglycan of PsB bacteria is similar to the peptidoglycan of a known pathogen, Streptococcus pyogenes.
Whereas EnB bacteria are Gram(-) TLR4-active because their membrane contains the active lipopolysaccharide LPS.
This LPS is active when interacting with TLR4, a receptor found on many immune cells.
It is assumed that antigen causing inadequate response of skin immune system originates from fragments of peptidoglycan forming cell wall of psoriagenic bacteria.
And when this antigen gets into bloodstream, it is taken up by blood neutrophils. Firstly, these neutrophils endocytose bacterial products in blood. Then, they are attracted to inflamed skin. Finally, they may undergo NETosis (self-destruction) in inflamed skin.
Action of one from two factors SP1 and SP2 is sufficient for chronically elevated level of kPAMP in blood. And, consequently, psoriasis maintenance.
Therefore long-term and stable remission of psoriasis is possible only with normalization of kPAMP concentration in blood.
And such normalization is only possible when both small intestine permeability for bacterial products and small intestinal bacterial overgrowth (SIBO) level are within normal limits.
SIBO in Psoriatic Patients: Research Findings
Medical professionals define SIBO (small intestinal bacterial overgrowth syndrome) as an excess concentration of parietal small intestine microbiome above the norm. Researchers conducted the first studies of the small intestinal microbiome in psoriatic patients between 2009 and 2011. During this period, they administered a classic SIBO test to 121 psoriatic patients and a control group of 43 healthy individuals.
Key Results:
- The data revealed a clear correlation between SIBO levels and the type, severity, and duration of psoriasis.
- Investigators detected SIBO in 78% of the patients.
- The patients showed an average total microbial count of 3×10⁶, which significantly exceeds the 1,1×10³ count found in the control group.
Psoriagenic Bacteria and Enhancing Bacteria at SIBO
Pathogenic (including EnB bacteria, for example Klebsiella spp. and E.coli) and psoriagenic bacteria were detected in the majority of patients. In 65% of patients, bacteria of genus Enterococcus (mainly Enterococcus faecalis) were found – on average 2×105, in 9% – Streptococcus pyogenes, in 30% – viridans streptococci. In the control group, these types of bacteria were not detected (Peslyak 2012c, Gumayunova 2009a, Gumayunova 2016, Nesterov 2009). In the following years, such studies were performed on many psoriatic patients. SIBO with pathogenic (including enhancing) and psoriagenic bacteria was almost always found.
To understand the model better, please review the following abbreviations and terms:
| PAMP | Pathogen-associated molecular patterns (in particular kPAMP ) |
| PsB | Psoriagenic bacteria – species of bacteria with PG-Y peptidoglycan |
| EnB | Gram(-) TLR4-active bacteria = Enhancing bacteria |
| kPAMP | LPS, PG, bacDNA |
| LPS | Lipopolysaccharide |
| PG | Peptidoglycan |
| bacDNA | Bacterial DNA |
| SIBO | Small intestine bacterial overgrowth |
Detailed in (Peslyak & Korotky 2020) and in SIBO (small intestinal bacterial overgrowth) in psoriatic disease..
Bibliography
Korotky N, Peslyak M. (2020). Blood metagenome in health and psoriasis. Front. Med. 7:333 doi:10.3389/fmed.2020.00333
Gumayunova NG. Syndrome of small intestine bacterial overgrowth at psoriatic disease against blastocystic invasion. Dissertation, 2009, 169 p, (rus), link.
Gumayunova NG, Nesterov AS, Potaturkina-Nesterova NI. Small intestine bacterial overgrowth syndrome and psoriatic disease. Monograph, 2016, 156 p. ISBN 9785888665923 (rus). link.
Nesterov AS. Features of pathogenesis and therapy of chronic dermatoses at blastocystic invasion. Dissertation, 2009, 298 p. (rus). link.
Pagano J. Healing psoriasis: The natural alternative., 2008, 352 p, ISBN: 9780470267264
Peslyak MY. Model of pathogenesis of psoriasis. Part 1. Systemic psoriatic process, 2012, 84 p., ISBN 9785905504020, link
Peslyak MY. Model of pathogenesis of psoriasis. Part 2. Local processes. 2012, 110 p., ISBN 9785905504044. link
Peslyak MY, Gumayunova NG, Nesterov AS, Potaturkina-Nesterova NI. (2012). Small intestine microflora at psoriasis. Its possible role in pathogenesis, Conference 2012: “Psoriasis – a global health challenge”, Dermatol Ther 2,10, S12. doi: 10.1007/s13555-012-0010-x
Peslyak MY, Korotky NG. “Metagenomes of blood and psoriatic skin. Research project.”, 2019, 67 p., ISBN 9785905504068, DOI: 10.5281/zenodo.2667680.
Peslyak MY, Korotky NG. “Psoriasis as netopathy. Model of pathogenesis with unique netosis role.”, 2020, 73 p., ISBN 9785905504082, DOI: 10.5281/zenodo.4310085.