## 4 Discussion
### Ibd  
#### 4.2.1. Pathophysiological Pathways of Inflammation and Oxidative Stress  
Genetic factors appear to play an important role in IBD pathogenesis. Multiple genes are reported to be associated with increased risk for IBD. However, aside from the genetic factors, gut microbiota imbalance, environmental factors and immunological abnormalities are implicated in the pathogenesis of IBD [3]. Gut microbiota seems to have an important role in the initiating events leading to IBD, as illustrated in the difference of gut microbiota composition between healthy study participants and IBD patients [65]. Although genetic background is considered a major part in the pathogenesis of IBD, recent studies in twins, with one healthy twin and the other an IBD patient, demonstrate the importance of environmental factors on the onset of IBD. Specifically, the differences in gut microbiota between the twins seem to explain why one twin suffers from IBD whereas the other does not [66]. The use of antibiotics leads to changes in the composition of gut microbiota and is also described as an initial part in the pathogenesis of IBD [67]. Furthermore, changes in diet may induce inflammatory responses leading to IBD onset [66]. Studies have further analyzed these gut microbiota imbalances, known as dysbiosis. _Clostridium_ spp. was significantly increased in IBD patients, whereas _Roseburia_ spp. and _Phascalorctobacterium_ spp., though abundant in healthy individuals, remained significantly low in IBD patients [68]. _Roseburia_ enhances the production of regulatory T-cells, thus expressing an anti-inflammatory effect in the intestinal tract [69]. _Phascalorctobacterium_ produces propionic acid, a short-chain fatty acid with known anti-inflammatory effects [70]. The significantly lower concentration of both bacteria in the gut microbiota of IBD patients may contribute to the disease's etiology. Furthermore, _Clostridium septum_ group, a major bacterial group of gut microbiota, shows differences between healthy individuals and IBD patients in remission. _Faecalibacterium prausnitzii_, a dominating bacteria of _Clostridium septum_ group, show lower concentration in gut microbiota of IBD patients with both active disease and disease in remission [71; 72]. Moreover, low concentration of _F. prausnitzii_ in the ileum of surgically treated patients with IBD is a risk factor for endoscopic recurrence. As a result, _F. prausnitzii_ has shown promise when administered as a probiotic. It appears to protect IBD patients from relapse due to the anti-inflammatory effects that have been reported both in vitro and in vivo [73]. Recent articles on IBD epidemiology show a significant increase of CD's prevalence in the developed world, as a result of progressive industrialization [74]. This fact underlines the crucial role that environmental factors play in IBD pathogenesis. Diet remains a major risk factor. High intake of fruits and vegetables is associated with a reduced risk of CD [75], whereas high intake of fatty and sugar-rich foods is associated with an increased risk of CD [76]. Moreover, artificial food additives seem to worsen intestinal inflammation as they interfere with the function of the gut barrier [75]. Another study shows that diets that contain high levels of animal protein induce a proinflammatory macrophage response [77]. Other environmental factors, implicated in the pathogenesis of IBD, are appendectomy, medications or other iatrogenic factors, psychological stress and smoking [78]. Although smoking worsens CD, it seems to produce a protective effect for UC, mainly due to the protective inhibitory effects that nicotine has on T-helper 2 cell function [74]. Immunological abnormalities in IBD patients result in epithelial damage. The main factors implicated in epithelial damage are abnormal mucus production and defective reparative mechanisms. Further expansion of inflammation is driven by intestinal flora with the involvement of immune cells that infiltrate into the lamina propria.