## 3 Results
### The Role of the Enteric Nervous System in IBS  
The enteric nervous system, which regulates gastrointestinal motor, sensory, mucosal barrier, and secretory responses, can be affected by adverse events in early life, psychological factors, or gastrointestinal infections, according to the biopsychosocial model developed to explain symptoms of abdominal pain and disordered bowel habit in IBS [4; 90]. Clinical evidence suggests that mental disorders are important factors in the development and progression of IBS, a disease with multiple causative factors [91]. Early life stress is one of the most common factors in the deterioration of IBS patients [92]. This stress may come from family, work or other social environments, or it may be caused by individual personality factors (Figure 3). Figure 2: Multifactorial contributors to IBS: From stress to gut dysbiosis and altered GI function. We created this image with canvas. Functional magnetic resonance imaging (MRI) studies have also found heightened visceral stimuli response among IBS patients, with the increased activation of the anterior cingulate cortex, prefrontal cortex, and thalamus in response to rectal distention in most instances [93]. These responses also appeared to be modulated by anxiety and depression [94]. Neurotransmitters are responsible for sending messages throughout the body from neurons to target cells, including muscles, glands, and other neurons [95]. Histamine, serotonin (5-hydroxytryptamine, 5-HT), glutamate, \(\gamma\)-aminobutyric acid (GABA), dopamine, acetylcholine, and catecholamines are among the neurotransmitters that the enteric microbiota regulates crucially [96; 97]. Each of these biological substances affect the activity of the enteric nervous system either individually or collectively as part of the pathology of IBS [98]. 5-HT is one of the most extensively studied neurotransmitters in IBS research [99]. Enteric 5-HT stimulates inflammation, activates the immune system, changes gut motility, increases mucosal permeability, and enhances visceral hypersensitivity, all of which work together to activate IBS symptoms [99]. In fact, pharmacological treatments targeting 5-HT receptors are commonly used in contemporary clinical practice to treat IBS [100]. Overall, 5-HT and enteric microbiota are a viable focus for IBS research and medical treatment. Figure 3: The role of intestinal immune activation in IBS. We created this image with Canva. Several investigations were conducted to support the idea that a deficiency in 5-HT production and release is linked to IBS. Among the most effective methods for examining this relation were gene knockdown and gene transformation. Researchers state that when intestinal 5-HT production decreases, the intestinal lining weakens, which eventually causes constipation or clogging and raises 5-HT levels in the gut [101]. One theory is that people with IBS have enterocytes that lack the 5-HT transporter (SERT). Another theory centres on the reduced quantity of enterochromaffin cells in the gastrointestinal tract of those who experience IBS [102]. 5-HT, essential for gastrointestinal motility, has a positive effect on information transmission to the central nervous system, and once released, can activate both intrinsic and extrinsic primary afferent neurons. Via SERT, 5-HT is reabsorbed by enterocytes and converted to 5-hydroxy-indole acetic acid (SHIAA), which limits its effects. The idea that 5-HT plays a key role in the development of IBS symptoms is further supported by the successful testing of therapeutic approaches which focus on different 5-HT receptors in IBS [103]. Studies show chronic increases in enterochromaffin cells in people who developed post-infectious IBS compared to people exposed to an acute enteric infection but who recovered, providing some of the first information regarding the potential role of 5-HT metabolism in IBS.