Pathogenesis (disease development)
It is thought to have a multifactorial genesis. Studies of colitis patients showed that a Western-oriented diet – low in complex carbohydrates as well as dietary fiber – resulted in a significantly higher risk of disease compared with the traditional Japanese diet. To date, however, there is no scientifically proven diet that reduces the risk of developing ulcerative colitis. Only breastfeeding (> 6 months) is considered to have a proven preventive effect. For the pathogenesis of ulcerative colitis, the barrier disorder of the intestinal mucosa plays a role, as a result of which misdirected immune reactions occur. Among the proinflammatory cytokines, tumor necrosis factor (TNF) plays a key role. Following are comments on the possible role of diet in ulcerative colitis.
Importance of dietary fiber
Dietary fibers-cellulose, pectins, lignin, plant gums as well as mucilages-are carbohydrates of plant origin. They occur in nature in soluble and insoluble forms. Celluloses belong to the insoluble dietary fibers and have a high swelling capacity due to their water-binding capacity. They thus increase the volume of ingested food and increase stool weight. Soluble dietary fibers, such as pectins and plant gums, form viscous solutions and have an even higher water-binding capacity than insoluble dietary fibers. By prolonging intestinal transit, reducing stool frequency, increasing water retention and increasing stool weight, soluble fibers counteract diarrhea and thus high fluid and electrolyte losses [5.1]. Dietary fiber – abundant in all cereal products, especially whole grains, legumes, vegetables such as salads and sprouts, fruits and nuts – cannot be broken down by the digestive secretions in the small intestine and therefore pass undigested into the large intestine. There, with the help of bacteria in the colonic mucosa, they are broken down into short-chain fatty acids, which are absorbed to a considerable extent and have a positive effect on the microorganisms of the colonic mucosa. Depending on the type of fiber supplied, there is an improvement in the growth rate and metabolic activity of different bacterial strains of the intestinal flora [5.1]. Accordingly, dietary fiber is essential for optimal intestinal function.
Low dietary fiber consumption
Through studies in colitis patients, it was found that patients consumed significantly small amounts of fruits rich in soluble fiber in the period before disease onset [4.2]. The notion that a low dietary fiber content promotes the development of ulcerative colitis is thus confirmed.
Sulfur-containing amino acids
Sulfur-containing amino acids are found, for example, in eggs, cheese, milk, nuts, as well as cabbage vegetables. If consumption of these foods occurs, the sulfides produced during bacterial breakdown of sulfur-containing amino acids damage the mucosa of the colon in some people. It is suspected that insufficient detoxification during the degradation of sulfur-containing amino acids or increased formation of sulfides is responsible for damage to the superficial mucosal layers of the colon and thus for the development of ulcerative colitis [4.2]. Therapeutic studies have shown that sulfur-containing amino acids or their degradation products influence the metabolism of the colonic mucosa to a high degree. In addition to their drug treatment, colitis patients should avoid foods rich in sulfur-containing amino acids. As a result, there was a clear reduction in disease activity. In addition, the number of acute episodes of ulcerative colitis decreased substantially in patients [4.2].
Nutritive Allergens
In infancy, the mucosal barrier of the intestine is not fully mature, making the intestine more permeable to macromolecules such as proteins as well as bacteria that cause infection. For this reason, infants often experience hypersensitivity reactions after eating certain foods. Infants fed with breast milk are much less likely to be affected by allergies to food components than non-breastfed infants. Breast milk has several factors that protect against allergy.This is due to the faster maturation of the child’s intestinal mucosa, which protects the digestive tract from infection-causing bacteria and thus reduces the absorption rate of food antigens. Protection from allergies extends well into childhood. Since those individuals who were not breastfed as infants are more likely to develop ulcerative colitis, the protein of cow’s milk is thought to be of particular importance as a nutritive allergen in the development of ulcerative colitis. In addition, antibodies against milk proteins can often be found in colitis patients. If infants are fed cow’s milk, there is an increased risk of allergy due to the still incomplete mucosal barrier of the child’s intestine. On first contact, the immune system regards the proteins or protein cleavage products contained in the milk – allergens – as foreign bodies and consequently forms antibodies – sensitization [4.2]. A renewed supply of the specific antigen leads to an antigen-antibody reaction. As a result, increased mediators such as histamines are released from the tissue mast cells of the intestinal mucosa. In most cases, due to the immaturity of the intestinal mucosa, infants have only small amounts of the enzymes necessary for histamine cleavage or they are completely absent. Due to the insufficient cleavage, the histamine concentration inside the intestine increases. High histamine concentrations in the colon damage the intestinal wall by weakening the immunological defenses of the colon mucosa and negatively affecting cell growth. In addition, histamine stimulates intestinal peristalsis and thus accelerates intestinal transit, reducing the absorption of water in the colon and causing abdominal pain, bloating, and diarrhea. Damage to the colon wall is associated with mucosal inflammation as well as impaired intestinal mucosal barrier function. The increased permeability of the child’s intestine promotes the uptake of pathogenic bacteria and germs – unphysiological malcolonization of the colon. The impaired barrier function leads to the transfer of bacteria and endotoxins from inside the intestine into the lymph and portal blood. This increases the risk for infections. Finally, the inflammatory as well as tumor-like changes of the colon mucosa result in impaired absorption of nutrients and vital substances (macro- and micronutrients) and thus inadequate macro- and micronutrient utilization [4.2]. Affected are:
- Vitamin A, D, E, K
- Calcium
- Magnesium
- Sodium chloride
- Potassium
- Iron
- Zinc
- Selenium
- Essential fatty acids
- Proteins
Such mucosal damage triggered by cow’s milk protein and the resulting consequences – inflammation, bacterial overgrowth, as well as infections – in early childhood usually manifest between the ages of 20 and 40 and represent the onset of ulcerative colitis. Since an infant’s risk of allergy is genetically determined, children of parents in whose families allergies are common are particularly susceptible to food intolerances. For this reason, in addition to cow’s milk, foods with known high allergenicity, such as eggs, wheat, nuts, chocolate, and citrus fruits, should be completely avoided during the child’s first year of life. In this way, the risk for mucosal damage and thus the development of ulcerative colitis can be significantly reduced [4.2].
Further
Similarly, an association between the occurrence of ulcerative colitis and increased consumption of animal protein and saturated and trans fatty acids seems possible.
Etiology (Causes)
Similar to Crohn’s disease, the etiology (cause) of ulcerative colitis is unknown. Currently available findings suggest that genetic factors such as allergenic antigens, infections, and autoimmune phenomena, as well as combinations of these causes-multifactorial genesis-are responsible for the mode of development. Furthermore, a genetic predisposition to the disease – familial accumulation – is discussed, and factors such as viruses, bacteria, psyche and nutrition seem to be important. Biographical causes
- Genetic burden – familial clustering.
- Ethnic origin – Europeans have a higher risk than Africans or Asians.
- Delivery by caesarean section (cesarean section; risk increase for inflammatory bowel disease 20%).
- Breastfeeding – Children who were breastfed for at least 6 months have a 25% lower risk of developing ulcerative colitis during their lifetime than those who were breastfed for a shorter period or not at all.
- Left-handed people have an increased risk
- Autoimmune phenomena, mechanisms – malfunction of the immune system – inability to distinguish between endogenous and exogenous structures, which are subsequently attacked by immune cells as well as autoantibodies; the autoimmune reaction leads to inflammation as well as functional impairment of the intestinal mucosa – there are changes in the bacterial flora of the mucosa of the large intestine as well as disturbances in the absorption of vital substances (micronutrients)
Behavioral causes
- Nutrition
- Dietary factors and dietary components, especially:
- Low consumption of complex carbohydrates or dietary fiber (low-fiber diet).
- High consumption of refined carbohydrates, animal protein, saturated fatty acids and trans fatty acids.
- Nutritive allergens, in particular the proteins of cow’s milk are essential – people who were not breastfed as infants and fed on cow’s milk are more likely to develop ulcerative colitis
- Micronutrient deficiency (vital substances) – see prevention with micronutrients.
- Dietary factors and dietary components, especially:
- Consumption of stimulants
- Alcohol (woman: > 40 g/day; man: > 60 g/day).
- Psycho-social situation
- Hygiene situation – regular contact with stabled animals or their excreta in the first year of life is statistically associated with a halving of the risk of developing ulcerative colitis by the age of 18 (hypothesis: lack of confrontation with parasites and microbial toxins increases the risk of “misprogramming” the immune system, leading to autoimmune diseases)
Disease-related causes
- Depression and anxiety
Medication
- Repeated and early use of antibiotics, especially those with a broad spectrum of activity.
- Taking non-steroidal anti-inflammatory drugs (NSAIDs).
- TNF blockers (biologics that neutralize tumor necrosis factor alpha): etanercept: adjusted hazard ratio of 2.0 (95% confidence interval 1.5 to 2.8); no increased risk was detectable for infliximab and adalimumab.
Environmental exposure – intoxications (poisonings).
- Environmental factors – influence of bacteria, viruses as well as pollutants leading to infections as well as inflammation of the intestinal mucosa [4.2].
