## 6 Diarrhea to Disorder: Tracing the Path from _Campylobacter jejuni_ Infection to PI-IBS
jejuni_, perpetuated by low-grade mucosal inflammation, which emerges as a secondary consequence of this disruption in the epithelial barrier in PI-IBS. The primary symptom of loose stools in PI-IBS patients suggests a reduction in the duration of contact between ingesta and the absorptive surface area, potentially occurring alongside visceral hypersensitivity due to the hyperactivity of intrinsic primary afferent neurons [1]. Damage to the epithelium's cellular and paracellular components can initiate a cascade of alterations in the immune and neuromuscular systems [9]. These changes can subsequently affect gut motility and sensory perception, potentially playing a role in the onset of PI-IBS [9]. Alterations in TJ proteins leading to increased permeability could account for loose stools in PI-IBS patients, irrespective of any change in contact time. It is significant to mention that these observations represent the inaugural set of paracellular ion permeability measurements in the context of PI-IBS. Beyond the role of active ion secretion, diarrhea observed in IBS-D may also arise from a maladaptive mechanism [48]. The ENaC is the primary sodium absorption system in the distal colon and rectum. Prior research has shown that ENaC-dependent sodium absorption is notably diminished in cases of lymphocytic colitis, contributing to diarrhea [48]. This dysfunction of ENaC points to a significant pathomechanism within the large intestine, illustrating its involvement in conditions such as ulcerative colitis and campylobacteriosis, where impaired sodium absorption plays a pivotal role in the manifestation of diarrheal symptoms [48]. Functional and expression analyses of the sigmoid colon have identified claudins (1-5 and 8), occludin and tricellulin as crucial constituents of TJ that dictate the epithelial barrier's function in the colon [48]. Recent studies have highlighted that, among these, only claudin-1, along with epithelial resistance, tended toward a reduction in IBS-D, whereas the expression levels of other strand-forming claudins remained unchanged [48]. Furthermore, the invasion of luminal bacterial antigens like LOS into the mucosal layer has been identified as a significant trigger for mucosal inflammation [1, 7]. This inflammation compromises the integrity of the intestinal barrier by stimulating cytokine release, which deregulates tight junctions and fosters epithelial leaks [1, 17]. Consequently, it creates a deleterious cycle, where the interplay between microbial infection and host responses exacerbates intestinal dysfunction, illustrating the possible complex pathogenesis of PI-IBS. Although the O-antigen typically associated with bacterial lipopolysaccharide (LPS) is absent in the LOS of most C. _jejuni_ strains, the lipid A component of this truncated LPS molecule alone functions as a highly effective TLR-4 agonist [72]. Furthermore, sialylated forms of LOS are implicated in triggering severe manifestations of campylobacteriosis and its post-infectious complications, including GBS and PI-IBS. Therefore, the distinct components of the LOS molecule lay a foundational understanding of the varied presentations of intestinal diseases and the emergence of post-infectious sequelae in human hosts [72]. The prevailing understanding of the pathophysiological mechanisms behind PI-IBS posits that exposure to pathogenic organisms precipitates alterations in the gut microbiome [7]. PI-IBS is characterized by elevated levels of neutrophils and mast cells within the colonic mucosa, indicative of an altered immunity. Recent studies have identified that deacetylase, encoded by _C. jejuni_ and akin to bacterial sirutin (_SIP_), plays a pivotal role in activating human neutrophils during infection. This sirutin is secreted into neutrophils, where it binds to and deacetylates the host's histones, thereby fostering neutrophil activation and the generation of neutrophil extracellular traps (NETs).