Following gastroenteritis 7–31% of adults develop persistent low-grade inflammation and IBS-like symptoms [15–18]. A study of a large outbreak of waterborne infection with Campylobacter jejuni and Escherichia coli O157 in Walkerton, Ontario yielded 228 cases of postinfectious IBS and 581 controls who had fully recovered. This study found a number of single nucleotide polymorphisms that distinguished postinfectious IBS patients from infected controls who had fully recovered [19]. The relevant genes were CDH1 coding for E-cadherin, a tight junction protein controlling gut permeability, Toll-like receptor (TLR) that mediates the cellular response to bacterial DNA, and IL-6 [19]. TLRs are normally downregulated to avoid inappropriate activation of the immune system by gut commensals [20]. Recently increased expression of TLR-4 has been reported in females with IBS, predominately of mixed or diarrhea-predominant IBS [21]. Increased intraepithelial and lamina propria lymphocytic infiltration, together with an increase in enteroendocrine cells, have also been reported in bowel biopsies obtained from postinfectious IBS patients [18]. These changes can persist for up to 12 months and are associated with increased mucosal permeability [15, 18]. In children with IBS, immune cells presence in the rectal mucosa was associated with a higher availability of 5-HT with higher 5-HT content and lower SERT mRNA compared to control subjects suggesting that mucosal inflammation may induce peripheral sensitization [22]. Bacterial gastroenteritis and Henoch–Schonlein purpura during early childhood can lead to development of IBS-like symptoms in later life [23, 24]. Bowel inflammation and pain in early childhood may lead to alteration in afferent signal processing due to neuroplasticity which can manifest in later life with functional pain during psychosocial stress.

Studies using fluorescent in situ hybridization to detect bacterial 16s RNA suggest that there is an increase in bacteria within the mucus layer in IBS patients [25]. Recently great advances have been made in understanding the microbiota through the development of culture-independent technologies and, in particular, metagenomics. There is great diversity and interpersonal variation in the bacterial species and strains present in the gut microbiota. Although studies of fecal microbiota in IBS are limited, a recent pediatric study reported a significantly greater percentage of the class γ-proteobacteria especially Haemophilus parainfluenzae in IBS patients. A Ruminococcus-like microbe was also more common in IBS subjects compared to controls in this study [26]. Several adult studies have reported reduced biodiversity of gut microbiota in IBS patients [27].

Abnormal rectal, colon, and small bowel motility has been implicated in IBS pathophysiology. Interpretation of colon motility studies in adults with IBS is hampered by a relatively primitive understanding of normal colon motility and its intrinsic variability. Abnormalities in colon motility and abnormalities in response to food and stress have been reported in patients with IBS [28]. Abnormalities in small bowel motility such as repetitive bursts of contractions or clusters, prominent high amplitude waves in the terminal ileum, and an exaggerated jejunal motor response to a meal have also been reported in adults with IBS [28, 29].

There is also a suggestion that IBS patients handle small bowel gas differently and there is slow transit of gas directly infused into the small bowel in adults with IBS [28]. Abdominal bloating and flatulence can also result from higher colonic fermentation in IBS [28, 30, 31]. Some patients without evidence of small bowel bacterial overgrowth can benefit from treatment with unabsorbable antibiotics [32], which raises the question of a qualitative change in bowel bacterial flora in IBS.

Serotonin (5-hydroxytryptamine: 5HT) is secreted in copious amounts by the gut enteroendocrine cells and serves as a critical messenger for GI fluid secretion and motility. It activates at least five different receptor types, and the 5-HT₃ and 5-HT₄ receptors are the most extensively studied in IBS [33]. The transporter of 5-HT (SERT) mediates the reuptake of 5-HT by the neurons and crypt epithelial cells and terminates its action.

Plasma 5-HT concentration is elevated in IBS patients [34] and the proportion of 5-HT secreting enteroendocrine cells is elevated in the GI tract in postinfectious IBS patients [15]. Increased rectal mucosal 5-HT concentration has also been reported in children with IBS. Presence of low-grade inflammation was associated with higher 5-HT concentration in rectal mucosa in this study [22]. Symptom relief by serotonergic agents including 5HT₃ antagonists and 5HT₄ agonists provides additional support for a possible role of 5-HT in IBS pathophysiology [35].

Familial aggregation and twin studies suggest that there may be a genetic predisposition to developing IBS [36, 37]. Twin studies have shown that the concordance rate for IBS is higher in monozygotic compared to dizygotic twins [38]. However, presence of IBS in the respondent’s parents made a much larger contribution to the risk of having IBS than did the presence of IBS in one’s twin, suggesting social learning may be more important than the environmental factors in determining illness behavior [38]. Family members of IBS patients are more likely to have the condition, compared to their spouse controls. To date, nearly 60 genes involved in different pathways including serotonin, adrenergic, inflammation, and intestinal barrier function have been studied to determine whether specific genetic variants may be associated with IBS [39]. Interleukin 10 is an anti-inflammatory cytokine and fewer IBS patients have the high IL-10 producing (G/G) genotype compared to healthy controls [36]. Four different studies have explored the association of SERT gene polymorphism in IBS [36]. SERT is important for terminating the GI activity of 5-HT. The wild type l/l polymorphism results in normal function, whereas the presence of the short allele (s/l or s/s) results in impaired SERT function. As a group, SERT polymorphism was similar in healthy subjects and IBS patients, but some differences were observed in subgroups of IBS patients, and these differences could be population specific.

Community-based studies in adults have shown that IBS patients are indistinguishable from the rest of the population in terms of psychological comorbidities [40]. Higher psychological comorbidities have been reported in a subset of IBS patients who seek medical help [40]. Patients with psychosomatic disorders such as depression have activation of the immune system and elevated CRP [41]. Adults who develop postinfectious IBS are more likely to develop depression [42] and depressive symptoms have also been linked to relapses of colitis [43] and disease activity [44] in IBD patients. It is not clear if the depression is the result of chronic ill health or leads to the development of IBS. In children social learning of illness behavior can also contribute to the development of IBS; children of mothers with IBS are more likely to seek medical help for functional gastrointestinal symptoms [45]. Children with IBS who have significant psychological comorbidities run a more protracted illness course and are less likely to respond to treatment [46].