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Previous studies have elucidated that lacking TLR5, the antigen recognition receptor for detecting bacterial flagellin, in murine models, along with the natural occurrence of single nucleotide polymorphisms (SNPs) in the Tlr5 gene in humans and pigs, is linked to significant alterations in intestinal microbial composition, the development of IBD, and the onset of metabolic syndrome [1, 2]. Animals with TLR5 deficiency develop colitis associated with dysbiosis and exhibit a slightly thinner, disorganized mucus layer [3]. However, in prior studies, the precise mechanisms underlying the interaction between innate immunity and the microbiota in regulating mucus layer homeostasis have remained unclear. The present study aims to pinpoint changes in microbiota and biochemical dynamics resulting from a disrupted TLR5 pathway.
Methods: Piglets born to nulliparous German Landrace sows were genotyped and screened for a known SNP (C1205T) associated with impaired TLR5 functionality [3]. Animals were sacrificed two weeks post-weaning. We collected scraped mucus samples from various intestinal locations of these piglets. Subsequently, glycan profiles, protein content, and gut microbiota in the mucus from the ileum, colon, and cecum of weaned piglets were analyzed.
Results: Different sections of the intestine displayed unique glycan profiles, protein content, and microbiota composition. In all our analyses, we observed slight differences between mucus samples from wild-type and TLR5-deficient animals. However, the most significant disparities were found in the ileum. TLR5-deficient animals exhibited lower levels of N-acetylhexosamine (HexNAc) glycans and less complex core 4 O-glycans in ileum. Moreover, at the pro-
tein level, we detected reduced levels of mucin 2 protein and Secretory TFF (trefoil factor family) peptide (TFF2) in the ileum mucus of TLR5-deficient animals.
Conclusions: A complex relationship exists between innate immune recognition, the microbiota, and the physiological homeostasis of the gut. Disrupting intrinsic factors, such as antigen recognition receptors, can result in alterations to the physiology of the mucosal barrier, including the mucus layer. This disruption can make the host more susceptible to developing intestinal inflammatory complications following exposure to stress or infection.