## 3 Host-Pathogen Interactions in _Campylobacter_ Infections: Understanding the Link to PI-IBS
jejuni_ with intestinal cells damages the differentiated cells located at the tips of the villi and halts the cell cycle in the proliferating cells within the crypts [26]. This disruption leads to villous atrophy, culminating in the hallmark presentation of bloody diarrhea associated with the infection. In vivo studies have speculated on the impact of _Campylobacter_ cytolethal distending toxin (_CdtB_) and potential mechanisms such as small intestinal bacterial overgrowth and the depletion of interstitial cells of Cajal (ICCs) [27; 28]. The cytotoxic effects of _CdtB_, which reduce ICCs and alter the gut microbiome, may explain the short-term pathophysiology of PI-IBS. ICCs play a crucial role in regulating gastrointestinal motility by generating and propagating electrical slow waves, and they facilitate communication between the autonomic nervous system and smooth muscle cells (Table 1) [27]. Numerous studies have highlighted that a combination of factors, including the depletion of interstitial cells of ICCs, changes in the metabolism of enterochromaffin cells (notably in the secretion of serotonin [5-HT] and peptide YY) and an increase in activated mast cells, are implicated in abnormalities in intestinal neuro perception as well as disruptions in absorption, secretion and motility [17]. Upon mechanical or chemical activation of enterochromaffin cells, serotonin engages with receptors on various cell types, including afferent nerve fibers and enterocytes [29]. This interaction stimulates motility and the secretion of bicarbonate and chloride, as well as modulating pain perception [29]. Moreover, serotonin is implicated in promoting mucosal inflammation, as it interacts with serotonin receptors on a diverse array of leukocytes, highlighting its multifaceted role in gastrointestinal function and immune response. People diagnosed with PI-IBS display increased levels of postprandial serotonin following meals compared to healthy subjects and patients with IBS-C [30]. Additionally, a reduced serotonin turnover rate has been noted in the rectal mucosa of patients with both PI-IBS and IBS-C, evidenced by a low ratio of 5-hydroxyindoleacetic acid to 5-hydroxyryptamine (5-HT), suggesting a deficiency in serotonin recycling [27; 30]. The synthesis of serotonin (5-HT) is regulated by the host and gut commensals, particularly those within the spore-forming _Clostridiales_ order of the _Frimicutes_ phylum [27]. _Campylobacter jejuni_-Induced Disruptions: Intestinal Permeability, Immune Dysregulation and the Pathogenesis of PI-IBS  
This section delves into the specific disruptions induced by _C. jejuni_, including increased intestinal permeability, immune system dysregulation and their consequential roles in the pathogenesis of PI-IBS. Upon attachment and invasion into human intestinal epithelial cells (IECs), _C. jejuni_ manipulates the host's cytoskeletal regulation to optimize its invasive capabilities [31]. After successfully invading, _C. jejuni_ is found within cytoplasmic compartments termed _Campylobacter_-containing vacuoles (CCVs) [31]. Pathogens' virulence factors can compromise the epithelial barrier and enhance intestinal permeability by activating myosin light-chain kinase, which facilitates the degradation of tight junction (TI) proteins, disrupts actin functionality and triggers apoptosis in intestinal epithelial cells (IECs). Epithelial barrier integrity is maintained by cell-to-cell adhesion, largely governed by TJ. In the [PERSON] cohort, genetic variations in the E-cadherin gene (_CDH1_) were linked to an increased risk of PI-IBS [32]. Several in vivo and in vitro studies have further revealed that disruptions in the barrier and subsequent bacterial translocation are associated with the degradation of occludin and claud-4, reductions in zonula occludens proteins and elevated expression of myosin light-chain kinase (MLCK), which is known to mediate barrier dysfunction [10; 33]. In