Expression of Main Toll-Like Receptors in Patients with Different Types of Colorectal Polyps and Their Relationship with Gut Microbiota.

Sama Rezasoltani,Abbas Yadegar,Hamid Asadzadeh Aghdaei,Mohammad Reza Zali,Delisha Stewart,Ehsan Nazemalhosseini Mojarad,Reza Ghanbari,Mehdi Azizmohammad Looha

doi:10.3390/ijms21238968

Abstract

Abnormal activation of Toll-like receptor (TLRs) signaling can result in colon cancer development. The aim of this study was to investigate the expression of important TLRs in different histological types of colorectal polyps and evaluate their relationship with intestinal microbiota. The expression levels of TLR2, 3, 4, and 5 were analyzed in intestinal biopsy specimens of 21 hyperplastic polyp (HP), 16 sessile serrated adenoma (SSA), 29 tubular adenoma (TA), 21 villous/tubulovillous (VP/TVP) cases, and 31 normal controls. In addition, selected gut bacteria including Streptococcus bovis, Enterococcus faecalis, Enterotoxigenic Bacteroides fragilis (ETBF), Fusobacterium nucleatum, Porphyromonas spp., Lactobacillus spp., Roseburia spp., and Bifidobacterium spp. were quantified in fecal samples using absolute qRT PCR, and, finally, the association between TLRs and these gut microbiota- was evaluated by Spearman’s correlation coefficient. Higher expression of TLR2 and TLR4 in VP/TVP and TA, and lower expression levels of TLR3 and TLR5 in all type of polyps were observed. The differences in TLR expression patterns was not only dependent on the histology, location, size, and dysplasia grade of polyps but also related to the intestinal microbiota patterns. TLR2 and TLR4 expression was directly associated with the F. nucleatum, E. faecalis, S. bovis, Porphyromonas, and inversely to Bifidobacterium, Lactobacillus, and Roseburia quantity. Furthermore, TLR3 and TLR5 expression was directly associated with Bifidobacterium, Roseburia, and Lactobacillus quantity. Our results suggest a possible critical role of TLRs during colorectal polyp progression. An abnormal regulation of TLRs in relation to gut microbial quantity may contribute to carcinogenesis.

Highlights

Colorectal cancer (CRC) is one of the most common cancers, and accounts for almost half a million deaths annually worldwide [1,2]
TLR2, TLR3, TLR4, and TLR5 mRNA expression levels were evaluated in clinical biospecimens of normal, hyperplastic polyp (HP), sessile serrated adenomas (SSA), VP/TPV, and tubular adenoma (TA) groups by relative qPCR and based on relative expression (RQ) levels, where normal tissue expression was set as the reference after all signals were normalized to β–2-microglobulin (Figure 1)
The noteworthy point was that the RQs of TLR2, TLR3, TLR4, and TLR5 were significantly different among histologically different colorectal polyp types compared to samples from normal participants (p-value < 0.001) (Table 2)

Summary

Introduction

Colorectal cancer (CRC) is one of the most common cancers, and accounts for almost half a million deaths annually worldwide [1,2]. The majority of CRC cases (~60%) arise via the conventional pathway, with ~20% arising from the serrated pathway and ~20% from an alternate pathway [5]. These distinct molecular pathways dictate the different precursor lesions, such as the conventional pathway resulting in CA and the serrated pathway with sessile serrated adenomas (SSA) [4,5]. Previous evidence suggests that gut bacteria may be a major factor involved in colon cancer development [8], distinct contributions through CAs or SSAs have not been studied simultaneously. In spite of the vast body of research surrounding TLRs, there is a lack of evidence on differentiating levels of TLR expression in different types of colorectal polyps as precursors of CRC [15,17]

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