Inflammatory bowel disease
Inflammatory bowel disease is a group of inflammatory conditions of the colon and small intestine, with Crohn's disease and ulcerative colitis being the principal types. Crohn's disease affects the small intestine and large intestine, as well as the mouth, esophagus, stomach and the anus, whereas UC primarily affects the colon and the rectum.
Signs and symptoms
In spite of Crohn's and UC being very different diseases, both may present with any of the following symptoms: abdominal pain, diarrhea, rectal bleeding, severe internal cramps/muscle spasms in the region of the pelvis and weight loss. Anemia is the most prevalent extraintestinal complication of inflammatory bowel disease. Associated complaints or diseases include arthritis, pyoderma gangrenosum, primary sclerosing cholangitis, and non-thyroidal illness syndrome. Associations with deep vein thrombosis and bronchiolitis obliterans organizing pneumonia have also been reported. Diagnosis is generally by assessment of inflammatory markers in stool followed by colonoscopy with biopsy of pathological lesions.Causes
IBD is a complex disease which arises as a result of the interaction of environmental and genetic factors leading to immunological responses and inflammation in the intestine.Diet
People living with IBD are very interested in diet, but little is known about the impact of diet on these patients. Recent reviews underlined the important role of nutritional counselling in IBD patients. Patients should be encouraged to adopt diets that are best supported by evidence and involve monitoring for the objective resolution of inflammation.A 2022 study found that diets with increased intake of fruits and vegetables, reduction of processed meats and refined carbohydrates, and preference of water for hydration were associated with lower risk of active symptoms with IBD, although increased intake of fruits and vegetables alone did not reduce risk of symptoms with Crohn's disease. A 2022 scientific review also found generally positive outcomes for IBD patients who adhered to the Mediterranean diet.
Dietary patterns are associated with a risk for ulcerative colitis. In particular, subjects who were in the highest tertile of the healthy dietary pattern had a 79% lower risk of ulcerative colitis.
Gluten sensitivity is common in IBD and associated with having flareups. Gluten sensitivity was reported in 23.6% and 27.3% of Crohn's disease and ulcerative colitis patients, respectively.
A diet high in protein, particularly animal protein, and/or high in sugar may be associated with increased risk of IBD and relapses.
Bile acids
Emerging evidence indicates that bile acids are important etiological agents in IBD pathogenesis. IBD patients have a consistent pattern of an increased abundance of primary bile acids such as cholic acid and chenodeoxycholic acid, and a decreased abundance of secondary bile acids such as lithocholic acid and deoxycholic acid.Microbiota
The human microbiota consists of 10–100 trillion microorganisms. Several studies have confirmed that the microbiota composition is different in patients with IBD compared to healthy individuals. This difference is more pronounced in patients with Crohn's disease than in those with ulcerative colitis. In IBD patients, there is a decrease or absence of beneficial bacteria such as Bifidobacterium longum, Eubacterium rectale, Faecalibacterium prausnitzii, and Roseburia intestinalis, while harmful species like Bacteroides fragilis, Ruminococcus torques, and Ruminococcus are more abundant.The activation of reactive oxygen species and reactive nitrogen species leads to oxidative stress for both host cells and the gut microbiome. Consequently, in IBD, there is a microbial imbalance, known as dysbiosis, characterized by an increase in functional pathways involved in the microbial response to oxidative stress. This oxidative stress can promote the growth of certain species such as R. gnavus. Another opportunistic bacterium called A. muciniphila contributes to IBD development and is more prevalent in individuals lacking NOD-like receptor 6. Both R. gnavus and A. muciniphila are bacterial species that are more abundant in IBD.
Patients with IBD often exhibit stronger antibody and T-cell responses to microbial antigens. The gut microbiome employs various approaches to interact with the host immune system. For instance, B. fragilis, which is symbiotic in humans, can transfer immune regulatory molecules to immune cells through the secretion of outer membrane vesicles. This mechanism plays a protective role in IBD by activating the non-classical autophagy pathway, dependent on Atg16L1 and NOD2 genes. B. thetaiotaomicron induces the differentiation of T regulatory cells to modulate gut immunity, thus increasing the expression of Gata3 and FoxP3 genes.
The colonization of Clostridium spp. can enhance the aggregation of RORγT+ FOXP3 Treg cells, which inhibit the development of Th2 and Th17 cells. Ultimately, this colonization could decrease the response of colonic Th2 and Th17 cells.
Also F. prausnitzii attracts CD4 and CD8a regulatory T cells.
E. coli Nissle 1917 has the capability to inhibit the growth of Salmonella and other harmful bacteria. It prevents these pathogens from adhering to and invading intestinal epithelial cells, which significantly reduces the likelihood of inflammation in the gut and may also prevent the onset of IBD.
Breach of intestinal barrier
Loss of integrity of the intestinal epithelium plays a key pathogenic role in IBD. Dysfunction of the innate immune system as a result of abnormal signaling through immune receptors called toll-like receptors —which activates an immune response to molecules that are broadly shared by multiple pathogens—contributes to acute and chronic inflammatory processes in IBD colitis and associated cancer. Changes in the composition of the intestinal microbiota are an important environmental factor in the development of IBD. Detrimental changes in the intestinal microbiota induce an inappropriate immune response that results in damage to the intestinal epithelium. Breaches in this critical barrier allow further infiltration of microbiota that, in turn, elicit further immune responses. IBD is a multifactorial disease that is nonetheless driven in part by an exaggerated immune response to gut microbiota that causes defects in epithelial barrier function.Oxidative stress and DNA damage
and DNA damage likely have a role in the pathophysiology of IBD. Oxidative DNA damage as measured by 8-OHdG levels was found to be significantly increased in people with IBD compared to healthy controls, and in inflamed mucosa compared with noninflamed mucosa. Antioxidant capacity as measured by the total action of all antioxidants detected in blood plasma or body fluids was found to be significantly decreased in people with IBD compared to healthy controls, and in inflamed mucosa compared with noninflamed mucosa.Genetics
A genetic component to IBD has been recognized for over a century. Research that has contributed to understanding of the genetics include studies of ethnic groups, familial clustering, epidemiological studies, and twin studies. With the advent of molecular genetics, understanding of the genetic basis has expanded considerably, particularly in the past decade. The first gene linked to IBD was NOD2 in 2001.Genome-wide association studies have since added to understanding of the genomics and pathogenesis of the disease. More than 200 single nucleotide polymorphisms are now known to be associated with susceptibility to IBD. One of the largest genetic studies of IBD was published in 2012. The analysis explained more of the variance in Crohn's disease and ulcerative colitis than previously reported. The results suggested that commensal microbiota are altered in such a way that they act as pathogens in inflammatory bowel diseases. Other studies show that mutations in IBD-associated genes might interfere with the cellular activity and interactions with the microbiome that promote normal immune responses. Many studies identified that microRNAs dysregulation involved in IBD and to promote colorectal cancer. By 2020, single-cell RNA sequencing analysis was launched by a small consortium using IBD patient biopsy material in a search for therapeutic targets.
According to an article published on Nature, ETS2 gene plays a vital role in the development of the disease.
Diagnosis
The diagnosis is usually confirmed by biopsies on colonoscopy. Fecal calprotectin is useful as an initial investigation, which may suggest the possibility of IBD, as this test is sensitive but not specific for IBD.Classification
Inflammatory bowel diseases are autoimmune diseases, in which the body's own immune system attacks elements of the digestive system. The chief types of IBD are Crohn's disease and ulcerative colitis. Several other conditions are variously referred to either as being inflammatory bowel diseases or as being similar to but distinct from inflammatory bowel diseases. These conditions include:- Microscopic colitis with subtypes
- * Collagenous colitis
- * Lymphocytic colitis
- Diversion colitis
- Behçet's disease
Differential diagnosis
Irritable bowel syndrome can present with similar symptoms as either disease, as can nonsteroidal anti-inflammatory drug enteritis and intestinal tuberculosis. Conditions that can be mistaken particularly for Crohn's disease include Behçet's disease and coeliac disease, while conditions that can be symptomatically similar to ulcerative colitis in particular include acute self-limiting colitis, amebic colitis, schistosomiasis and colon cancer. Other diseases may cause an increased excretion of fecal calprotectin, such as infectious diarrhea, untreated celiac disease, necrotizing enterocolitis, intestinal cystic fibrosis and neoplastic pediatric tumor cells.
Liver function tests are often elevated in IBD, and are often mild and generally return spontaneously to normal levels. The most relevant mechanisms of elevated liver functions tests in IBD are drug-induced hepatotoxicity and fatty liver.