Inflammatory bowel disease (IBD) is a disease of the intestinal tract and includes Crohn's disease (CD) and ulcerative colitis (UC). Incorrect functioning of the immune system in IBD leads to mucosal inflammation by the gut microflora resulting in leakage of the intestinal barrier. (Szkudlapski) In other words, there is a "loss of tolerance" to the normal gut flora. The diseases are characterized by symptoms which include but is not limited to diarrhea, constipation, rectal bleeding with bowel movement, bowel movement urgency, abdominal cramps and pain, fever, weight loss, and vomiting and nausea. The range of symptoms varies greatly depending on the person and the section of the bowel that is involved. Experts believe that while there are probably many reasons for an individual to develop IBD, 4 main reason capture most of the attention. These are microflora disturbances of the intestinal tract, genetic and epigenetic processes, what is called the "hygiene" hypothesis and the consumption of a Western diet.
Generally, if a person lives in a developed country, there is a much greater likelihood that he/she will develop IBD. In 2009, the World Gastroenterology Organisation released data on the prevalence of IBD in the world's population. They reported that the prevalence of "UC has been increasing since the Second World War and is now increasing in previous low incidence areas like Eastern Europe, Asia, and developing countries." The incidence of CD is less than 1 in 100,000 in Asia and South America, 1-3 per 100,000 in Southern Europe and Africa, 16 per 100,000 in Australia and New Zealand, 14 per 100,000 in Canada and 7 per 100,000 in Olmstead County, Minnesota. The Center for Disease Control and Prevention reports that in the United States 1/3 of the population is obese and 1.4 million people suffer from IBD.
The incidence of UC tends to be higher in urban areas than in rural areas and first rises in higher social classes. These rates tend to level out over time. Interestingly, for those that move to a developed country from a low incidence area, the incidence rate increases in those individuals. Patients that suffer from IBD also have the tendency to have higher incidences of other inflammatory diseases. Some of these diseases seem to be independent and others appear dependent on the development of IBD. These include arthritis, which is the most common, spondylitis, osteoporosis, mood disorders such as anxiety and depression, fatty liver disease, and others.
Many scientists believe that there is a genetic component but do not believe that genetics alone can explain the increase over the last hundred years. Further, it is believed there is a "multiple hit" phenomenon that precipitates disease. Meaning that there is more than one factor that is required to develop a disease state. Over the past several years, there have been any number of things that have been attributed to causing IBD. These include but are not limited to bacteria, metals, drugs, dietary components like fat and protein, fruits and vegetables, etc. Even with all of these factors that have been studied the true cause of IBD remains elusive.
Qin has proposed the incidence of IBD has been increasing over the past several decades because of the addition of, and consumption of, foods with saccharin (which is made from coal tar). The author does a good job of tracing the manufacturing and the ups and downs of distribution of the product after its creation in the late 1800s. Incidentally, the first real case of UC clusters were observed after 1888 which would correspond nicely to the first use of the chemical sweetener. One physician of the day had the foresight to suggest that the increasing rates of UC incidences were due to "some food additive. He stated that "maybe the cases of acute colitis were connected with the food supply; tinned or preserved foods might have something to do with it." In the early years, saccharin was used in canned foods as a preservative for vegetables, fruits and meats."". (Qin)
Through his research, Qin has come to the conclusion that sucralose (Splenda) may also contribute to IBD much in the same way that saccharin does. He explains that "both have the capacity to inhibit gut bacteria. This idea is supported by the way antibiotics inhibit bacteria and that saccharin is widely used in all kinds of food products. In addition, more and more chemicals are being used as additives in food that may be able to act directly, in a negative way, on gut bacteria causing IBD. Today, sucralose has the potential to be even more of an impact on the digestive system because it is more widely accepted as an additive than saccharin and has a higher acceptable daily intake that could result in more potent activity on the gut." The most recent studies of artificial sweeteners demonstrated that artificial sweeteners disturb the normal gut flora. (Azvolinsky) Abou-Donia demonstrated that for several weeks, the normal gut flora remained altered after exposure to sucralose.
An interesting premise one must take into account is that humans have not had long enough to adapt to the environmental changes in diet since agriculture and animal husbandry only developed around 10,000 years ago. In organisms, it is the failure to adapt to changes like these that can lead to disease. (Leone1) In another article, Leone et al. suggests that a major contributing factor to high rates of IBD is the intake of high fat and high carbohydrates common to Western-types diets in developing nations. She states the transition to this kind of diet correlates well to higher incidence rates of IBD. "Recent evidence has shown that shifts in dietary intake can lead to changes in the gut microbiota." In a person that is susceptible, those changes could lead to a case of IBD. She goes on to say that because the intestinal microbiota is plastic, the use of probiotics and dietary changes that includes low fat and low carbohydrates could prove beneficial. Probiotics could be used to resolve inflammation and improve microbial balance. (Leone 2) Furrie et al found that the use of a probiotic, in addition to, a prebiotic oligosaccharide that promotes probiotic growth, was an effective therapy against mucosal inflammatory markers in UC. From several studies, there is agreement among scientists that the diet and obesity can influence microbial populations. Turnbaugh found that in the microbiome, there is a shift towards abundant firmicutes which become the dominant lineage in the gut of the obese individual. This is diminished by subsequent weight loss and adiposity. A switch from bifidobacteria to other lineages result in increased translocation and intestinal leakage. (Wang)Incidentally, these experiments may pave the way for new therapies for obesity.
Bassaganya-Riera states that more investigation is needed on how influences from omega 3 PUFA can be applied to the clinical setting. His pig study demonstrated in experimental colitis that during a 7 day treatment of omega 3 PUFA and another fatty acid did not ameliorate UC but "favored a faster remission." Another study from 2010 showed a relationship between fatty acids in the cell membranes and remission of IBD.
As we stated above, the incidence rates if IBD is increasing in developed countries. Unfortunately, this is also true about other autoimmune diseases like type-1 diabetes and multiple sclerosis. Typically autoimmune disease is virtually unheard of in developing counties. Many experts cite the
"hygiene hypothesis" as being the reason for this. Initially, the "hygiene hypothesis" was linked to the ever increasing prevalence of allergic rhinitis in developing countries. Today, the "hygiene hypothesis" is linked to any number of diseases including autoimmune disease, encephalitis and cancer. Basically, the "hygiene hypothesis" explains while drastic measures of prevention like sanitation and disinfection have lowered the incidence of infections and contagious disease, the prevalence of autoimmune disease has increased because of the use of these measures or products. Take for example, the use of antimicrobials like triclosan in soaps, body washes and even toothpaste. The use of these products as disinfectants are used daily by millions of people to "clean and disinfect" themselves and their living space. The downside of this is that by using these products our environments may be "too clean"! The "hygiene hypothesis" is based on the fact that living in "too clean" environments, with a less likelihood of coming in contact with pathogens or allergans, makes it unlikely that we can build a "tolerance" to these kind of agents. In countries where drastic measures are taken to control those pathogens and subsequent infection there is an emergence of allergy and autoimmune disease. (Okada)
Okada points out that the incidence of autoimmune disease can not just be from genetic differences. In Finland, the prevalence of diabetes is 6 times higher than in the population from the Karelian republic of Russia which borders it. Genetically, populations from these two regions are genetically similar. It has also been shown immigrants from a region with a low incidence rate of autoimmune disease that move to a region with a high rate of autoimmune disease, develop autoimmune diseases at the same incidence rate of the higher rate region. This is true of type-1 diabetes, multiple sclerosis, and lupus.
Another interesting proposal is that the "limited exposure to bacterial and parasitic pathogens of populations of very highly developed countries has contributed to the depletion of immunologic memory and the development of hypersensitivity mechanisms." (Szkudlapski et al) It has been suggested that the human and microbiota of the gut form a mutualistic relationship rather than a typical parasitic one. This of course serves an adaptive function because the microbiome lives in a very harsh environment in the human gut. On one hand, the host (in this case the human) allows commensal bacteria to populate the gut and on the other hand, the microbiota, has the ability to breakdown food particles and produce chemicals that are used by and are beneficial to the host. Another mutualistic relationship in the gut is the one that exists by humans and nematodes. The human gut is an ideal living environment for microbiota and helminthes. This is an adaptation which probably developed through time as humans evolved. Unfortunately, the use of antibiotics reduces good bacteria and nematodes that reside in the intestine. Because of the broad availability of a wide variety of medicines in developed countries, there is a lower incidence of parasitic infections in these populations. It is believed that these are two conditions that play a big part in the increasing rates of IBD and other autoimmune diseases.
Szkudlapski claims that dysbiosis occurs when there is an absence of helminthes in the gut in people of richer societies. This, he says, is one example of an alternative to the "hygiene hypothesis" and is called the "old friends" hypothesis. The "old friend hypothesis" describes early immune challenge of helminth infection may be beneficial. Recent studies show that helminths are able to form a tolerant environment for themselves to order to survive. To do this, they change how the immune system works in the gut and proceeds by suppressing immune processes. In experimental models, the transfer of helminths or their antigens into the guts of effected animals, resulted in limiting the development of chemically-induced colitis. In one experiment, chemically-induced colitis was resolved after immunization of Schistosoma mansoni egg antigen. (Hasby)
Whatever the cause of IBD, the problem is real and the prevalence is increasing. Scientists must find more and better ways to treat it and to treat towards a cure not just "remission ". As one can see from above, some of the alternatives for treatment may not sit well with patients. The recent studies, using helminths antigen seem positive and the procedure resolves the issue of being inoculated with live organisms. Right now, the long-term effects are not known and thus makes that kind of therapy prohibitive. Probiotic therapy is innocuous enough but much more research is needed to find out what strains of "good bacteria" are best to change the intestinal flora. Of course, resolving the issue related to the "hygiene hypothesis" needs to be explored further. It currently is not feasible to turn back time to rid the world of antimicrobial agents and disinfectants. Technology is going to have to advance to a point where these products are transformed to reduce the possibility of a "loss of tolerance" to normal environmental pathogens and gut flora with their use. Or these agents are going to need to be replaced with environmentally-friendly products entirely. As for diet, it is only recently that the general population began being concerned about the health problems associated with high-fat diets, one of which is obesity. Generally, research needs to clarify the relationship of IBD to high fat diets. Only then can a broad reaching program be developed that reaches effected populations in a clinical setting.
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