New information on subprocesses SP2 and SP2.1 (Peslyak, Korotky 2021).
Within the YN model of pathogenesis, these two subprocesses play a key role:
Subprocess SP2. Growth of Gram(-) TLR4-active and Gram+ NOD2-active bacteria in the small intestinal microbiome.
Subprocess SP2.1. Growth of psoriagenic PsB populations (subordinate to SP2)
Streptococcus sp. are almost always present in the small intestinal microbiome. They constitute a significant percentage of it both in normal conditions and in SIBO. This fact was first confirmed by studies by the REIMAGINE group (see Section A2.8 and Table A5 in the Supplement to (Peslyak, Korotky 2021).
This was confirmed by a new publication by the same REIMAGINE group on a much larger cohort. A duodenal examination with biomaterial aspiration was performed. The biomaterial was cultured (including on McConkey agar), as well as 16S rRNA sequencing and whole-genome sequencing (for a small proportion of participants).
Streptococcus sp. accounts for 20 to 35% of the small intestinal microbiome. The examination covered 483 (385+98) participants; a diagnosis of small intestinal SIBO (TBC greater than 10e3 CFU/ml) was made for 98 participants. For 32 participants, the TBC was greater than 10e5 CFU/mL. (Leite 2024 , Table 1, Fig. 2 – after the title of this article).
This same study emphasizes that the presence of SIBO correlates with a significant increase in the percentage of the genus Klebsiella (from the Enterobacteriaceae family), specifically two species: Klebsiella aerogenes and Klebsiella pneumoniae. As well as two strains of Escherichia coli (from the Enterobacteriaceae family), namely Escherichia coli K-12 and Escherichia coli BL21(DE3).
These two species and two strains are TLR4-active because they carry the LpxL and LpxM genes, i.e., they have LPS with lipid A with six acyl chains. (hexa-acyled). All strains (and substrains) whose genomes are available in the database https://www.kegg.jp/ contain these genes.
TLR4-active small intestinal bacteria are responsible for the production of LPS, which actively interacts with the TLR4 receptor of phagocytes (particularly neutrophils). This LPS activates blood neutrophils and accelerates their transition to a pre-neutral state.
Similar results on the percentage of Streptococcus sp. presence in the small intestinal microbiome were obtained in (Wang 2024). The higher percentage of presence is likely due to the fact that the biomaterial was collected into a passive capsule in the intestinal lumen. During aspiration, the biomaterial is typically collected near the small intestinal wall (sometimes with prior rinsing). (Fig. 2 B)
Two main goals in the treatment of small intestinal bacterial overgrowth (SIBO).
Goal 1: Return the concentration of Streptococcus sp. in the small intestinal microbiome (as well as other putative psoriasis bacteria) to normal (i.e., no higher than 10e3 CFU/mL).
Goal 2: Maximally eliminate TLR4-active bacteria from the small intestinal microbiome.
Bibliography
Leite G., Rezaie A., Mathur R. at al. Defining Small Intestinal Bacterial Overgrowth by Culture and High Throughput Sequencing. Throughput Sequencing. Clin Gastroenterol Hepatol. 2024 Feb;22(2):259-270 PMID 37315761.
doi: https://doi.org/10.1016/j.cgh.2023.06.001
Wang G., Menon S., Wilsack L. at al. Spatially and temporally precise microbiome profiling in the small intestine using the SIMBA capsule with X-ray tracking. Frontiers in Microbiomes, 2024, v. 3,
doi: https://doi.org/10.3389/frmbi.2024.1321624
Peslyak M. Y., Korotki N. G. “Psoriasis as netopathy. Model of pathogenesis with unique netosis role.” , 2021, 78 pages, ISBN 9785905504075,
DOI: https://doi.org/10.5281/zenodo.4310085