Fig. 2

Potential interconnected factors that regulate the manifestation of IBS symptoms. IBS has a multifactorial pathophysiology and multiple interrelated pathways can influence the manifestation of symptoms. External factors are dominant, but internal factors such as gut microbiome, gastrointestinal immune system and genetic makeup is also likely to be crucial for the development and progression of symptoms. Here we summarized potential external and internal factors and genetic findings linked to underlying pathophysiological mechanisms of IBS [6, 24, 26, 30, 96]. HPA, hypothalamic–pituitary–adrenal axis; ADRA, adrenoceptor-α; aINS, anterior insula; CDC42, cell division cycle 42; CDH1, cadherin 1; CGN, cingulin; CLDN, claudin; COMT, catechol-O-methyltransferase; CRHR1, corticotropin-releasing hormone receptor 1; FGFR4, fibroblast growth factor receptor 4; GLUL, glutamate-ammonia ligase; GPBAR1, G protein-coupled bile acid receptor 1; GRID2IP, GRID2-interacting protein; HTR, 5-hydroxytryptamine receptor; IL, interleukin; KLB, Klotho-β; mir, microRNA; NKRF, nuclear factor-κB-repressing factor; SCN5A, sodium voltage-gated channel α-subunit 5; SLC6A4, solute carrier family 6 member 4; TNF, tumour necrosis factor; TNFSF15, TNF superfamily member 15; TRPV1, transient receptor potential cation channel subfamily V member 1;; NCAM1, Neural Cell Adhesion Molecule 1; CADM2, Cell Adhesion Molecule 2; PHF2, PHD Finger Protein 2; DOCK9, Dedicator Of Cytokinesis 9