Crohn's disease and ulcerative colitis are inflammatory bowel diseases characterized by chronic non-proportional inflammation against normal gut bacteria. Although more than 200 genes related to the development of the disease are known today, genetics only explains about a third of the cases, with the environment being responsible for the rest. In fact, almost a hundred years ago, there were hardly any inflammatory bowel diseases in the world, even though the genes were always present. Various theories attempt to explain what in our environment is connected to the dramatic rise in the prevalence of inflammatory bowel diseases in Israel and the Western world. However, it is certain that the bacterial pattern in the gut plays a crucial role both in the development of the disease and in triggering exacerbations.
Normally, our intestines contain ten times more bacteria than cells in our body, and these bacteria are in a delicate balance among themselves and with our immune system through the release of small molecules that communicate between cells and bacteria. In fact, the metabolic product of all gut bacteria, which makes up more than 60% of the weight of solid stool, is higher than that of our liver. Each of us has a unique bacterial pattern in the gut (referred to as "microbiome") that remains relatively constant in a healthy state and is established after birth based on environmental exposure.
Chronic inflammation in Crohn's disease can result from the disruption of one or more of three main components: changes in the microbiome, increased permeability of the gut lining to microbiota, or alterations in the immune system. These changes can arise from both genetic and environmental factors, ultimately leading to the body's inability to effectively handle bacterial invasion, resulting in a strong but inefficient immune response. Prolonged inflammation causes damage to the intestinal lining, leading to typical symptoms such as diarrhea, abdominal pain, various absorption problems, and sustained damage to the intestines.
This is why anti-inflammatory drugs (such as steroids, immunomodulators, aminosalicylates, methotrexate, mercaptopurine, and infliximab) are effective in treating inflammatory bowel diseases. The concept is similar to treating the irritation caused by a grain of sand in the eye. An anti-inflammatory substance may alleviate pain and redness in the eye, but the foreign body (mimicking the bacterial invasion in the intestinal lining) doesn't disappear, and when the treatment ends, inflammation may recur.
Research has shown that the microbiome changes after the diagnosis of inflammatory bowel diseases, particularly during active disease. Microbiome diversity was found to be different in the feces of children with severe ulcerative colitis who responded to steroid treatment compared to those who did not respond, especially at the beginning of hospitalization.
Based on these findings, treatments that can affect the microbiome, such as probiotics, antibiotics, and fecal microbiota transplantation (FMT), have gained interest. Probiotic devices have been studied extensively, showing moderate effectiveness in ulcerative colitis but not in Crohn's disease. There is no clear consensus on the efficiency of probiotic therapy in inflammatory bowel diseases.
Similarly, there's renewed interest in using antibiotic devices for both Crohn's disease and ulcerative colitis. In Crohn's disease, some antibiotic regimens have shown improvement, and a cocktail of antibiotic devices might bring relief even in severe cases. However, this is mostly effective when administered orally, not through enema.
The transplantation of fecal microbiota, known as FMT, has also gained attention, particularly in cases of ulcerative colitis. It involves transferring healthy microbiota from a donor to the gut of a patient with the aim of restoring a balanced microbiome. While some cases have shown positive results, more research is needed to fully understand its effectiveness, safety, and potential side effects.
Due to the complexity and variability of individual responses, these treatments are usually considered in severe cases that do not respond to standard therapies. They should be administered within the framework of clinical trials to better determine their benefits and risks. It's important to note that while these treatments hold promise, they are not yet fully understood, and further research is required to establish their place in the treatment of inflammatory bowel diseases.