Role of Intestinal Microbiota in Ulcerative Colitis

Theoretical part
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2. The colonic environment
However, to avoid unnecessary detection of Gram‐positive commensal bacteria, IECs have
developed special mechanisms to tolerate the continuous presence of LTA molecules originating
from commensals by expressing TLR2 and co‐receptors at a limited level (Melmed et al.,
2003;Lebeer et al., 2010). The same mechanism has been observed for TL4 on IECs, in which
expression of TLR4 is down‐regulated to avoid hyper‐responsiveness to lipopolysaccharide (LPS)
(Table 2) from commensal Gram‐negative bacteria (Abreu et al., 2001).
In literature, immune regulatory effects of commensal bacteria through TLRs have been observed.
As an example, Hoarau et al. (2006) demonstrated that the supernatant of B. breve could cause
maturation of DCs through TLR2 pathway. This effect led to high levels of interleukin (IL)‐10
(inducer of regulatory T cells (Treg cells)) and low levels of IL‐12, in contrast to DCs stimulated with
LPS. Another Bifidobacterium species, B. longum, has shown to attenuate Tumor Necrosis Factor‐
alfa (TNF‐α)‐induced Nuclear factor kappa B (NF‐κB) activation and NF‐κB‐mediated IL‐8
expression through TLR9 (Ghadimi et al., 2010). Finally, a study by Geuking et al. (2011)
demonstrated that the colonization of mice with a completely benign commensal microbiota
(altered Schaedler Flora) resulted in activation of colonic Treg cells in lamina propria through TLR
signaling, which led to intestinal T cell homeostasis as reflected by the absence of T helper 1 cell or
T helper 17 cell responses.
Table 2: TLR recognition of Microbial Components
Microbial Components Species TLR Usage References
Triacyl lipopeptides Bacteria and mycobacteria TLR1 (Takeuchi et al., 2002)
Peptidoglycan Gram‐positive bacteria TLR2 (Takeuchi et al.,
1999;Schwandner et al.,
1999)
Fimbrillin Porphyromonas gingivalis TLR2/TLR4 (Davey et al., 2008)
Polysaccharide A Bacteroides fragilis TLR2 (Round et al., 2011)
Lipoarabinomannan Mycobacteria TLR2 (Means et al., 1999)
Porins Neisseria TLR2 (Massari et al., 2002)
Lipoteichoic acid Gram‐positive bacteria TLR2/TLR6 (Schwandner et al., 1999)
Lipopolysaccharide Gram‐negative bacteria TLR4 (Poltorak et al., 1998)
Flagellin Flagellated bacteria TLR5 (Hayashi et al., 2001)
Diacyl lipopeptides Mycoplasma TLR6 (Takeuchi et al., 2001)
CpG‐containing DNA Bacteria and mycobacteria TLR9 (Hemmi et al., 2000)
Not determined Not determined TLR10 ‐
Not determined Uropathogenic bacteria TLR11 (Zhang et al., 2004)