## 2 Key Factors in the Emergence of PI-IBS  
In the intricate landscape of gastrointestinal disorders, the emergence of PI-IBS presents a compelling case study of the dynamic interplay between infectious agents and host physiological responses. This review delves into the key factors in transitioning from a transient C. _ jejuni_ infection to the enduring perturbations characteristic of PI-IBS. Infectious enteritis (IE) is a well-recognized factor that increases the risk of developing IBS, specifically a subset known as PI-IBS. The incidence of PI-IBS associated with _Campylobacter_ infections exceeds 20% [4]. The severity of _Campylobacter_ enterocolitis is known to influence the risk of developing PI-IBS, with factors such as bloody stools, hospitalization, and the duration of acute illness being correlated with higher risk [5]. However, the specific _Campylobacter_ lineages and underlying genetic factors contributing to PI-IBS remain poorly understood [6]. Factors predisposing individuals to PI-IBS encompass genetic predispositions (_TLR-9, IL-6_ and _CDH1_ genes), psychosocial elements (including stress, fatigue, anxiety and depression), diet, smoking, pathogenic infections (predominantly with _Campylobacter_) and its severity, stool frequency with diarrhea, antibiotic exposure, a younger age and females being more susceptible [4; 7; 22]. The utilization of antacids may escalate the severity of gastroenteritis by lowering stomach acid levels, which serve as a critical defense mechanism against ingested pathogens [23]. This reduction in stomach acidity could heighten the risk of developing PI-IBS by facilitating the survival and subsequent colonization of infectious agents in the gastrointestinal tract [23]. Recent clinical studies have found that individuals with _Campylobacter_ infections exhibit significantly elevated rates of anxiety, depression and smoking compared to those without such infections [4]. The likelihood of developing PI-IBS following a bacterial gastroenteritis event, for instance, with _Campylobacter_, varies widely from 4% to 46%, influenced by the diagnostic criteria for IBS, the specific pathogen involved and the length of the observational period [4]. Within the United States, PI-IBS is estimated to represent nearly 70% of _Campylobacter_'s total impact on human health, quantified in terms of Disability Adjusted Life Years (DALY) [4]. Recently, [PERSON] et al. showed that patients with AGE (acute gastroenteritis) had a significantly higher risk of developing PI-IBS than those with upper respiratory tract infections (URTI) [22]. The relative risk for PI-IBS after AGE was 4.16, with female patients at a higher risk (79%) than males (18%). _c. jejuni_ infection had the highest risk for PI-IBS. These findings underscore the increased risk of PI-IBS following AGE, especially in females with specific pathogens like _C. jejuni_[22]. Similarly, individuals with a history of anxiety and depression exhibit delayed recovery from PI-IBS over a follow-up period ranging from six to eight years [24]. The mechanism through which psychological factors heighten the risk of developing PI-IBS is not fully understood. Notably, it is becoming increasingly evident that interactions between the microbiota-gut-brain axis can profoundly influence the intestinal immune system, affecting the immune response to pathogens [24]. Chronic psychological stress compromises the immune system, altering cytokine secretion patterns and increasing infection susceptibility. Moreover, prolonged stress disrupts the balance between T helper-1 and T helper-2 (Th1/Th2) cells, accumulating myeloid-derived suppressor cells within the peripheral blood and bone marrow, leading to immunosuppression [24]. In a previous comprehensive study of a cohort exposed to contaminated drinking water (NoV, _Campylobacter_ spp. and _G. lamblia_), researchers prospectively evaluated the risk of developing PI-IBS, focusing on psychological factors and immune responses during the acute phase and one-year post-outbreak [24].