Currently, corticotropin-releasing factor (CRF), NOD-like receptor family pyrin domain containing 6 (NLRP6 or IDO1), nucleotide-binding oligomerization domain-containing protein 2 (NOD2), Toll-like receptor 4 (TLR4), and cytochrome P450 1A (CYP1a) have been associated with low butyrate levels and colonic mucosal inflammation in humans and animal model of IBS, demonstrating the effects of genomic background on cross-signaling (Vujkovic-Cvijin et al., 2015; Wang et al., 2016; Layunta et al., 2018; Manzella et al., 2018; Martin-Gallausiaux et al., 2018; Zhao et al., 2018; Yu et al., 2019). Here, TLR4 is linked to irritable bowel syndrome.