Inflammatory Bowel Disease (IBD) has two main subcategories, Crohn’s Disease (CD) and Ulcerative Colitis (UC). Crohn’s disease is chronic inflammatory condition of the gastrointestinal tract. Crohn’s is characterized by inflammation anywhere along the gastrointestinal tract – though most commonly found in the ilium and colon – resulting in episodes of chronic diarrhea or constipation eventually leading to chronic malnutrition. Ulcerative colitis differs in that is remains solely in the colon and has a different dysbiosis profile, this page will discuss Crohn’s not Ulcerative Colitis.
Crohn’s is a progressive condition with periods of active disease and remission. CD has shown a predominance for female involvement, though a growing number of males have been reported with the condition in recent years. CD is a disease of the Western world and is rarely found in developing nations. Crohn’s can strike at any age with most cases being diagnosed in the early adult years from 20- 40. There are instances of pediatric onset Crohn’s and research has shown some genetic involvement leading to possible hereditability. Childhood onset of Crohn’s is on the rise following the spread of the Western diet. (Freeman H.J., 2009)
It is not yet completely understood what creates the perfect storm for Crohn’s to develop. Current diagnosis is based on symptomatic expression and observed tissue damage, but what and where the shift from healthy gut to diseased gut starts and why is unknown. Hypotheses under consideration include long term undiagnosed food allergy including wheat, corn, and dairy, (Kawaguchi et al., 2015) and long term undiagnosed environmental allergy including seasonal pollens, pet dander, and dust mites.(Dutta et al., 2015) There are also studies that show a connection to food additives and preservatives.(Nickerson, 2015) A large population of scientists are focusing work on the layers of the microbiome, teasing apart how the immune system is involved. (Alipour et al., 2016) Another cadre of researchers is tackling the pathway of viruses which seem to have a large impact on disease initiation.(Carriere et al., 2014) Another camp is sorting out genetic susceptibility. (Baumgart et al., 2012)(Bhullar et al., 2014)(Salick et al., 2015)(Boukercha et al., 2015) Still others are diving in to how topics of stress, circadian rhythm, and mental health impact CD.(Michielan, A., & D’Incà, R.,2015)(Ananthakrishnan et al., 2014)(Kennedy et al., 2014)
Signs and Symptoms
Crohn’s disease is most often associated with bowel movement dysregulation specifically with periods of either explosive diarrhea or crippling constipation along with mucosal discharge. The lining of the small intestine becomes chronically inflamed resulting in a change in tissue structure and permanent scarring. These episodes are often associated with pain, nausea, and vomiting. The inflamed GI tract makes any absorption of nutrient content from diet nearly impossible and patients often experience malnutrition. These times of gastrointestinal dysregulation are commonly referred to as flares, where active inflammation is high. Within a flare there can be periods of relative calm and episodes of acute disease. Crohn’s patients can experience remission, where both physical inflammation and chemical markers for inflammation are recorded as within normal parameters. Periods of remission and relapse can vary from weeks and months to years in a cyclic nature. Remission does not imply cured as the genetic component of the disease is still present. (Baumgart J et al., 2012) At present, there is no cure for Crohn’s disease.
Who is affected?
Crohn’s disease is primarily a disease of Western style developed society with diet including high fat and carbohydrate content, excess antibiotic and pesticide use, and lifestyle induced stress as key factors. Rarely is the disease found in developing countries. Caucasian women are more likely to develop CD than men. Most cases of CD are diagnosed between the age of 20 and 40 years old with the majority of cases being diagnosed in the later portion of the timeframe, often after years of misdiagnosis. While CD is typically considered an adult onset disease there is a rising number of children effected by it as well. Pediatric onset Crohn’s has a different disease course and is often associated with a more debilitating progression. As with adult onset, incidence of pediatric CD are on the rise, especially in developing countries. (Hovde & Moum, 2012)
Crohn’s is found in much greater percentages in Northern hemisphere countries where a higher GDP correlates to a higher incidence of Crohn’s. What is perhaps more striking is that this world wide rise is directly connected to the change in diet from traditional style diet high in whole foods to western style diet heavy in processed foods. In South America the incidence of IBD is in the range of 2-10/100,000 similar to Asia with 5/100,000 compared to Europe with 0.5–10.6/100,000 depending on country then up to Canada 53.6/100,000 with and finally ending with the United States and 201/100,000. (Burisch et al., 2013)(Kappelman et al, 2013)(Dhalhamer et al, 2016)
Crohn’s disease develops as inflammation in the lining of the GI tract that can extend through the tissue thickness.(Freeman H. J., 2009) At the onset of disease, a patient may experience an infection of the GI tract from either an irritant or infectious agent resulting in excessive diarrhea or constipation. For an unknown reason this stimulates the immune system to attack the inherent microbiome causing dysbiosis.(Lewis et al, 2016) This microbial dysbiosis upsets the apple cart and once the innate immune system is breeched, the war is on. Crohn’s is classified as an autoimmune disease. Chronic inflammation from underlying undiagnosed allergy, a shifted microbiome that harbors infectious agents, or other environmental factors coupled with an as yet undiscovered genetic predisposition may contribute to ongoing progression of disease.(Craven et al, 2012)(Segal AW, 2016)
Disease progression is measured in the severity and length of time with active flares and acute episodes, followed by periods of remission. (Speckhorse et al., 2012) How many, how long, and how severe each flare is, is wholly dependent on the patient. As the disease progresses, periods of remission grow shorter and time in active flare grows longer. CD is not limited to the GI tract and symptoms may include arthritis, gall stones, kidney stones, pancreatitis, lymph system involvement, and urinary tract infections.(Baumgart et al, 2012) As the GI tract becomes more involved, remembering that the GI tract goes from the mouth to the anus, patients begin to show signs of malnutrition and begin to acquire comorbidities, including skin lesions, hair loss, bone density loss, muscle mass loss, hormonal dysregulation, blood pressure dysregulation, cardiac episodes, and in women menstrual dysregulation.(Freeman et al, 2009)
The progression of Crohn’s is hard to detail as to the length of time from onset of symptoms to diagnosis is often long after initial disease onset. Symptoms for early CD include diarrhea, nausea, gastric pain, fatigue, weight loss, and general malaise. (Hovde & Moum, 2012) As inflammation continues, the gut is unable to heal, creating granuloma scar tissue in a linear cobblestone appearance inside the intestinal lumen. This inflammation flattens the microvilli, leaving no room for the microbiota or mucosal layer to function. As the inflammation continues, the intestine becomes fat wrapped in white adipose tissue, making a stiff mass. As the tissue degrades, holes called fistulae develop in the intestine which leak fluid into adjoining organs or the body cavity. Occasionally these fistulae work their way outward leaking intestinal fluid through skin lesions. As the lumen of the intestine remains inflamed, stricturing – or significant narrowing of the lumen can occur creating sites for obstruction. Sometimes sections of the intestine can bulge and adhere to another section of the intestine forming an abscess. Due to the specificity of the GI tract, disease progression may depend on cell similarity along the GI tract and in other organs of similar tissue types.(Freeman et al, 2009) Some variants of CD seem to be specific to new tissue creating post-surgical recurrence. (Hovde & Moum, 2012) Crohn’s disease has been called a metastasizing disease because of this ability for Crohn’s like lesions to appear in all organs containing epithelial tissue. (Siroy & Wassman, 2012)
Diagnostic Criteria and Tests
While there are diagnostic criteria developed for Crohn’s, teasing Crohn’s out from other similar conditions can be difficult. It’s recurring/remission pattern, especially in early stages makes it a moving target. Crohn’s Disease is often scaled on the Crohn’s Disease Activity Index (CDAI) (Freeman, 2008) Diagnostic procedures include colonoscopy, endoscopy, CT, and MRI. Diagnostic tests include CBC, C-Reactive Protein, erythrocyte sedimentation rate, iron/anemia test, and fecal blood tests. None of these tests are within themselves diagnostic, rather a cluster of tissue changes, metabolic disruptions, and inflammatory markers are assessed. (Vermiere et al., 2010)
An example of an online CDAI calculator can be found at:
Another assessment used is the Harvey Bradshaw Test, which can be found here:
Classification of Crohn’s Disease:
The Montreal scale for classification of Crohn’s disease is used to assess physical progression of disease and help inform treatment protocols.(Speckhorse et al., 2012)
Image: Baumgart & Sandbourn, 2012
Image: Gklavas et al, 2017
Current courses of treatment
Crohn’s disease is currently treated by a range of pharmaceutical medications including aminosalicilates, antibiotics, corticosteriods, immunosuppresants, and biologics.(Sobardo et al., 2016) Due to the fistulizing and stricturing nature of CD, surgery is often required to maintain minimal gut pass through. Surgery is not effective in controlling the progression of disease, and there is even evidence that show that ilial resection causes faster progression of disease than other less invasive treatments.
GI Tract outline
When working with a patient with Crohn’s disease it is important to remember two things. First, the gastrointestinal tract includes all of the organs from mouth to anus and Crohn’s effects the entirety of the GI tract. “Gums to Bum” is often heard among support groups. Crohn’s disease is specifically differentiated from Ulcerative Colitis in that UC only effect the colon. Second is that Crohn’s effects the full span of the thickness of the intestinal wall mucosa to serosa, where UC only effects the mucosa. Another important distinction between CD and UC is that because CD spans the muscle layers, gastric motility becomes a greater issue in long term remission as the peristaltic motion is effected when the smooth muscles become involved.(Michielan, A., & D’Incà, R., 2015),(Baumgart & Sandborn, 2012)
Irritable Bowel Disease is linked to over 100 different genetic loci that may be regulatory to development and progression of the disease. Progression of the disease is thought to become more severe if a larger genetic component is present than if not. (Posovszky et al, 2014)
“Single-nucleotide polymorphisms in the nucleotide-binding oligomerization domain gene (NOD2) may play an important role in CD. The NOD2 gene regulates barrier function, autophagy, and hyposensitization of the gut to normal microflora and health of Paneth cells. Three alleles of NOD2 (Arg702Trp, Gly908Arg, and 980fs981) have been studied extensively. A large segment of CD patients in Western countries carry at least one mutated NOD2 allele. Persons with 2 of the mutated alleles have a 20- to 40-fold higher risk of developing CD. Thus, mutations in NOD2 gene are strong genetic risk factors for CD.” (Khan, Samson & Grover, 2017)
The NOD2 gene encodes for multiple processes within the innate immune system. Among these operations is the secretion of antibacterial molecules from Paneth cells. Ogura et al., suggest in a 2003 paper, that the NOD2 gene as expressed in the cytosol of the Paneth cells somehow switches off the production of the antimicrobial agents produced. This change is found in the cells in the ilial portion of the intestine more than any other part and may be partially causative for producing the shift in microbiome associated with this gene.(Baumgart et al., 2012)(Bhullar et al., 2014)(Salick et al., 2015)(Boukercha et al., 2015)(Posovszky et al., 2013)
In another example of the genetic component of Crohn’s, a 2017 paper discusses how impaired tryptophan metabolism impacts IBD. The study reports a significant correlation between low serum TRP and active disease. The colleagues discuss three specific reasons why TRP serum levels are found to be lower in IBD patients than the healthy cohort. Digestion and absorption of dietary TRP is difficult at best for IBD patients. TRP is taken up in small intestine, the area most effected by CD.
-Tryptophan is absorbed into the cell via BOAT1 transporters which reside mainly in the small intestine with some in the colon. In IBD patients, mRNA miscodes BOAT1 transporters so TRP can’t enter intestinal epithelial cells.
-Lactobacillus is a bacteria found in abundance in the healthy gut biome. It is well noted in other literature that the ratio of lactobacillus in IBD patients is significantly perturbed. Lactobacillus is used to snip TRP from ingested proteins making them available for the BOAT1 transporters.
-TRP hydroxylase enzyme is used in the pathway that leads to the production of serotonin and eventually melatonin. Ninety percent of the TRP hydroxylase enzyme is expressed in the cell of the ilium.
In an adaptive process the cell redirects the KYN amino acid pathway, which metabolizes ninety percent of the TRP absorbed to produce more of the quinolinic acid QUI substrate versus the normal picolinic acid (PIC). QUI is a precursor to nicotinamide. This pathway is initiated by the oxidation of TRP to KYN using the IDO1 enzyme. IDO1 is used to add a hydroxyl group to the fifth carbon of the molecule in a rate limiting irreversible step making kynurenine from tryptophan. This enzyme is upregulated by excess pro-inflammatory cytokines abundant in the CD gut. The authors hypothesize that this upregulation is an adaptation to draw more TRP into the KYN pathway to create more NAD for energy production.
The change in serum TRP was not found to change significantly given changes in dietary intake. This is most likely because of the changes in the BOAT1 transporters in the ilium not allowing dietary TRP to enter the cells coupled with the lack of appropriate levels of microbiome bacteria to free TRP from luminal sources. (Nikolaus et al., 2017)
Crohn’s disease is characterized by three changes in the tissue of the small intestine, the thickening of the entirety of the intestine wall, distinct cobblestone like inflammation of the luminal wall, and extra deposits of white adipose tissue surrounding the cavity side of the effected area. This external adipose tissue is thought to have a direct connection to the internal scarring.
Cytokine Inflammation Network
The inflammation in the intestinal lumina is associated with specific cytokine networks. In a recent paper the authors detail the cytokine profiles corresponding to both CD and UC. Crohn’s shows a greater expression of Th2 network where UC is primarily regulated by the Th1 network. IBD shows inflammation linked to IL-12, IL-18, IL-21 and IL-27 while CD also shows upregulation of IL-17, IL-23 and IL-32. This is differentiated from UC in that UC shows upregulation of IL-5, IL-13, IL-15, and IL-33 instead. Interestingly, CD also show upregulation of IL-12 in noninflamed tissue samples as well. UC does not.(Nemeth et al., 2017) There is some evidence that suggests Crohn’s is also linked to Th17 cytokine networks.(Brand s, 2009) Several bacteria has been associated with inducing cytokine responses of those networks that regulate Crohn’s disease. Among those are E.Coli, Salmonella, and H Pylori, all implicated in the environmental factors that may precipitate the onset of Crohn’s. (Wilson M, et al., 1998)
Image:Fink et al, 2012
Fat wrapping is an issue specific to Crohn’s disease. GI surgeons define active disease tissue by the external fat wrapping as well as the internal cobblestone scaring specifically in the ilium but also in the colon. The degree of fat wrapping is correlated to the degree of luminal involvement often indicative of fistulae or stricturing. Fat wrapping occurs when white adipose tissue deposits encase a segment of ilium in effect strangling the underlying tissue. One opinion is that the inflammation from the compression of the underlying tissue incites a reaction from the adipocytes releasing their own inflammatory agents. What is not understood and still needs further study is why the fat wrapping begins, whether it is in reaction to luminal inflammation or if it is the cause of it. If it is the cause, why the body deposits the adipose there also needs more investigation. (Shelley-Fraser, G. et al., 2012) (Peyrin‐Biroulet et al, 2007)
As the inflammation from the fat wrapped tissue continues, the fragile villi begin to lose definition. The internal structures within the villi – the capillaries, nerves, and lymph vessels – also lose definition and atrophy. As the disease progresses and inflammation continues the epithelial cells of the villi begin to disintegrate leaving gaps in the tissue allowing larger particles to pass into the abdominal cavity.
Peyer’s Patches and Paneth Cells
Two cell types in the small intestine of specific interest to Crohn’s disease, Paneth cells and Peyer’s Patches. Adjacent to the microvilli are small crypts in the tissue leading down to where new cells develop from stem cells. Lining the bottom of the crypts are the Paneth cells. Paneth cells are specialized to secrete protein designed to destroy luminal bacteria by apoptosis. They are the body’s pesticide producers. The NOD2 gene tells the Paneth cells how to produce the appropriate protein. The mutation to the NOD2 gene present in the iliem and colon of CD patients means that this protein does not induce bacterial apoptosis and cell death. (Ogura Y, et al., 2003) Peyer’s patches is part of the “gut associated lymphoid tissue or GALT”. These patches of lymphoid follicules are covered by a layer of epithelia tissue. Several of the epithelial tissue cells are modified to be M cells, or microfold cells. These M cells are responsible for collecting bacteria from the mucosal layer of the small intestine. M cells then transfer the bacteria to the lymphoid tissue to incite a reaction from the immune system. The NOD2 gene also effects the cells of the Peyer’s Patches by determining how many M cells are present at the location of each patch. More M cells mean more bateria are able to be passed into the follicles. Some bacteria use the follicle area to reproduce. In CD, the mutation ot the NOD2 gene upregulates the production of M cells, thereby increasing the amount of immunological load the system is dealing with. This in turn escalates the autoimmune response increasing inflammation.(Hugot & Barreau, 2010)
Image: (Muniz et al, 2012)
There appears to be significant microbial and mucosal dysbiosis involved with CD. The gastrointestinal tract is home to a vast colony of symbiotic bacteria, viral components, and yeasts. This tiny zoo makes up our microbiome. It lives in and on top of a gooey slime produced in concert with the epithelial cells of small and large intestine. Two issues arise when discussing the gut biome and CD, first the change in bacteria from symbiotic to pathogenic, and second the change in physiology of the severely chronically inflamed epithelial tissues.
The gut biome is host to a large number of the members of the domain Bacteria. Of the 30 or so phyla in the group, the human biome is made up of primarily Firmicutes and Bacteriodetes. The players from team Firmicute include Listeria, Staphylococcous, Acetobacterium, Clostridium, and Heliobacteria; while Bacteroidetes include B. Fragilis and B. Thetaiotaomicron. The intestinal permeability experienced during active CD allows these bacteria free access to the rest of the body. (Carriere J, et al., 2014)
In a typical gut the good bugs like Lactobacillis and Bifidobacteria well outnumber the bad guys like E. Coli, Salmonella and others. (Zhang et al., 2015) These bacteria do all sorts of things for us like breaking down food to liberate vitamins and other metabolites, adjust the pH of the GI tract, fight invading pathogens, and assist the immune system. (Riviere et al., 2016) In a recent study, Pascal et al. (2017), were able to distinguish at least eight different strains of bacteria specific to the microbiome of the Crohn’s patient that are indicative of active disease. These included Fusobacterium and Escherichia. Escherichia is a commonly occurring bacteria, one finds a significant overgrowth in the CD patient. Other common bacteria found in the microbiome have also been found in overgrowth in the fecal samples of CD patients, including Candida Albicans.
Possible infectious bacteria and viruses have been implicated in the pathogenesis of CD. Included in this list are a specific form of E. Coli that adheres to the epithelial cells, MAP or Mycobacterium avuim paratuberculosis, Yersinia, Listeria, Heliobacter, and Epstein Barr. (Carriere J et al., 2014)
Common complications of Crohn’s disease include both fistula – passages made between hollow organs of the body, and strictures – narrowing of the luminal cavity of the hollow organ involved. As Crohn’s can occur anywhere along the GI tract, fistula and strictures can as well. More often they are found within the abdominal cavity, however fistula can also extend to the external skin surface, erupting as skin abscesses usually around the lower abdomen. Strictures can cause life threatening bowel obstructions if not addressed. These complications are the most common reason cited for surgical intervention. (Lewis & Maron, 2010)
Psychosocial factors implicated in Crohn’s Disease pathology
A Western diet heavy in meats, saturated fats, carbohydrates, and processed foods has been strongly implicated in the rapid rise in incidence rate of Crohn’s disease around the world. There has been a trend upwards in the reported cases of Crohn’s in developing countries post westernization. (Agus et al., 2016) Theories as to the leading causes include the addition of artificial additives and preservatives, higher fat and grain components, along with a restriction in fresh foods creating changes to the gut microbiome drastic enough to allow degradation of the mucosal layer. Much of the discussion centers around the change in macronutrient content and available prebiotic nutrients for the gut microbiome. It is well known that a diet high in processed foods including high fructose corn syrup, artificial sweeteners, and preservatives causes systemic inflammation. It is suspected that this shift away from whole foods coupled with genetic predisposition and a precipitating disruption in the gut microbiome such as a viral infection could tip the scales in the immune system toward the autoimmune disorder.
“An interesting concept indicates that ‘Western lifestyle factors’ trigger chronic intestinal inflammation or disease flares in a genetically susceptible host.” (Rogler et al., 2016)
Smoking significantly increases the progression of Crohn’s and may be causative in initiating disease. This finding is opposite of that for the other IBD disease Ulcerative Colitis which seems to respond positively to tobacco, though not cigarette use. (Ott et al., 2014)
Alcohol consumption is a major disruptor of the microbiome in the GI tract. Patients with Crohn’s disease are at greater risk for additional dysbiosis if they consume alcohol. (Engen et al., 2015)
Integration / Comorbidities
Because Crohn’s disease effects the entire GI tract, malnutrition is common among patients. These patients live in an almost permanent state of fasting. As such metabolic pathways must be addressed as processing in this state, even when food is being consumed. Depending on where the exact inflammation or resection has occurred will effect what macro/micro nutrients will need to be supplemented. (Ghishan & Kiela, 2014) Supplementing a Crohn’s patient must be done as much as possible with liquid formulae as much as possible for sublingual ingestion as a compromised GI tract will not be able to adequately digest a pill supplement. (Khan, Samson & Grover, 2017) Absorbtion of supplements are also impeded by removal of intestine and colon tissue as a result of surgical resections.
According to a 2014 paper published in the World Journal of Gastroenterology, Crohn’s patients are 2-3 times more at risk for Deep Vein Thrombosis (DVT) than the general population. This elevated risk is associated with intestinal inflammation, dehydration, and malnutrition. Most of the recorded DVT occurred in the leg and secondarily in the pulmonary artery. Because of the increased risk, CD patients should be followed by a cardiac physician as well. (Papa A, et al., 2014)
The liver is most at risk for comorbidities with IBD. The primary condition associated with IBD is Primary Sclerosing Cholangitis (PSC) with fully 80% of IBD patients also developing PSC. Repeated inflammation or chronic inflammation can cause scaring of the area surrounding the bile ducts in the liver. This scarring then slowly decreases the diameter of the duct making it harder to secrete bile into the digestive tract. This becomes a cycle as less bile in turn makes it harder to digest cholesterol, which is used to produce bile. The scaring can progress slowly. In approximately 40% of cases the gallbladder may also be involved.(Rasmussen H et al., 1997) Screening for liver conditions should be a regular part of any IBD treatment protocol.
Irritable Bowel Disease is increasing in incidence worldwide as the invasion of the western diet continues its march to developing countries. Crohn’s Disease is pathologically different from its cousin condition Ulcerative Colitis. While both are part of the Irritable Bowel Disease umbrella, progression and treatments are vastly different. Ubiquitous with the fat laden, artificial preservative filled, sugar driven diet of the Western world, IBD is reaching levels of presentation in the general population that are fast becoming a part of the Western disease profile along with the increase in obesity, cardiovascular disease, and diabetes. Crohn’s disease could be seen as the body’s attempt to shut out the toxic agents presented in the western diet and lifestyle.
Following are links to papers of interest to those including Complementary Alternative Medicine (CAM) in practices. Western treatment protocols are temporary at best for Crohn’s disease, achieving remission is often a difficult and arduous process. CAM modalities may in the near future prove to be as, if not more, effective at managing the progression of the disease while improving quality of life for effected patients and their sociological sphere.
Overview of CAM Treatments
Ng, S. C., Lam, Y. T., Tsoi, K. K., Chan, F. K., Sung, J. J. and Wu, J. C. (2013), Systematic review: the efficacy of herbal therapy in inflammatory bowel disease. Aliment Pharmacol Ther, 38: 854-863. doi:10.1111/apt.12464
Shang, H.-X., Wang, A.-Q., Bao, C.-H., Wu, H.-G., Chen, W.-F., Wu, L.-Y., … Shi, Y. (2015). Moxibustion combined with acupuncture increases tight junction protein expression in Crohn’s disease patients. World Journal of Gastroenterology : WJG, 21(16), 4986–4996. http://doi.org/10.3748/wjg.v21.i16.4986
Cannabis Induces a Clinical Response in Patients with Crohn’s Disease: A Prospective Placebo-Controlled Study. (2013, May 04).
Nagarkatti, P., Pandey, R., Rieder, S. A., Hegde, V. L., & Nagarkatti, M. (2009, October). Cannabinoids as novel anti-inflammatory drugs. from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2828614/
As with any chronic disease mental health must be considered as an important component of treatment and support. The following is a paper detailing incidence of depression linked with childhood onset Crohn’s disease.
Clark, J. G., Srinath, A. I., Youk, A. O., Kirshner, M. A., McCarthy, F. N., Keljo, D. J., … Szigethy, E. M. (2014). Predictors of Depression in Youth With Crohn Disease. Journal of Pediatric Gastroenterology and Nutrition, 58(5), 569–573. http://doi.org/10.1097/MPG.0000000000000277
Irritable Bowel Disease is the umbrella diagnosis for what specific diseases?
What is are the three underlying causes for Crohn’s disease?
What is the pathophysiologic tissue difference between Crohn’s Disease and Ulcerative Colitis?
Crohn’s Disease effects what part of the gastrointestinal tract?
Find questions referenced under Crohns Disease.
Center for Disease Control and Prevention (www.CDC.org)
Crohn’s and Colitis Foundation of Canada (www.ccfc.ca)
Crohn’s and Colitis Foundation of America (www.ccfa.org)
National Institutes of Health information (www.health.nih.gov)
Agus, A., Denizot, J., Thévenot, J., Martinez-Medina, M., Massier, S., Sauvanet, P., … Barnich, N. (2016). Western diet induces a shift in microbiota composition enhancing susceptibility to Adherent-Invasive E. coli infection and intestinal inflammation. Scientific Reports, 6, 19032. http://doi.org/10.1038/srep19032
Alipour, M., Zaidi, D., Valcheva, R., Jovel, J., Martínez, I., Sergi, C., … Wine, E. (2016). Mucosal Barrier Depletion and Loss of Bacterial Diversity are Primary Abnormalities in Paediatric Ulcerative Colitis. Journal of Crohn’s & Colitis, 10(4), 462–471. http://doi.org/10.1093/ecco-jcc/jjv223
Ananthakrishnan, A. N., Khalili, H., Konijeti, G. G., Higuchi, L. M., de Silva, P., Fuchs, C. S., … Chan, A. T. (2014). Sleep Duration Affects Risk for Ulcerative Colitis: A Prospective Cohort Study. Clinical Gastroenterology and Hepatology : The Official Clinical Practice Journal of the American Gastroenterological Association, 12(11), 1879–1886. http://doi.org/10.1016/j.cgh.2014.04.021
Baumgart, Daniel C, Sandborn, William J, Crohn’s Disease, The Lancet, Issue 9853, pages 1590-1605, November 2012 doi: 10.1016/S0140-6736(12)60026-9 http://dx.doi.org/10.1016/S0140-6736(12)60026-9 2018/06/16
Johan Burisch, Tine Jess, Matteo Martinato, Peter L. Lakatos, on behalf of ECCO -EpiCom; The burden of inflammatory bowel disease in Europe, Journal of Crohn’s and Colitis, Volume 7, Issue 4, 1 May 2013, Pages 322–337, https://doi.org/10.1016/j.crohns.2013.01.010
Bhullar, M., Macrae, F., Brown, G., Smith, M., & Sharpe, K. (2014). Prediction of Crohn’s disease aggression through NOD2/CARD15 gene sequencing in an Australian cohort. World Journal of Gastroenterology : WJG, 20(17), 5008–5016. http://doi.org/10.3748/wjg.v20.i17.5008
Boukercha, A., Mesbah-Amroun, H., Bouzidi, A., Saoula, H., Nakkemouche, M., Roy, M., … Touil-Boukoffa, C. (2015). NOD2/CARD15 gene mutations in North Algerian patients with inflammatory bowel disease. World Journal of Gastroenterology : WJG, 21(25), 7786–7794. http://doi.org/10.3748/wjg.v21.i25.7786
Brand S, Crohn’s disease: Th1, Th17 or both? The change of a paradigm: new immunological and genetic insights implicate Th17 cells in the pathogenesis of Crohn’s disease, Gut 2009;58:1152-1167.
Brotherton, C. S., Taylor, A. G., Bourguignon, C., & Anderson, J. G. (2014). A High Fiber Diet May Improve Bowel Function and Health-Related Quality of Life in Patients with Crohn’s Disease. Gastroenterology Nursing : The Official Journal of the Society of Gastroenterology Nurses and Associates, 37(3), 206–216. http://doi.org/10.1097/SGA.0000000000000047
Carrière, J., Darfeuille-Michaud, A., & Nguyen, H. T. T. (2014). Infectious etiopathogenesis of Crohn’s disease. World Journal of Gastroenterology : WJG, 20(34), 12102–12117. http://doi.org/10.3748/wjg.v20.i34.12102
Craven M, Egan CE, Dowd SE, McDonough SP, Dogan B, et al. (2012) Inflammation Drives Dysbiosis and Bacterial Invasion in Murine Models of Ileal Crohn’s Disease. PLOS ONE 7(7): e41594. https://doi.org/10.1371/journal.pone.0041594
Dahlhamer JM, Zammitti EP, Ward BW, Wheaton AG, Croft JB. Prevalence of Inflammatory Bowel Disease Among Adults Aged ≥18 Years — United States, 2015. MMWR Morb Mortal Wkly Rep 2016;65:1166–1169. DOI: http://dx.doi.org/10.15585/mmwr.mm6542a3.
Dutta, A. K., & Chacko, A. (2016). Influence of environmental factors on the onset and course of inflammatory bowel disease. World Journal of Gastroenterology, 22(3), 1088–1100. http://doi.org/10.3748/wjg.v22.i3.1088
Engen, P. A., Green, S. J., Voigt, R. M., Forsyth, C. B., & Keshavarzian, A. (2015). The Gastrointestinal Microbiome: Alcohol Effects on the Composition of Intestinal Microbiota. Alcohol Research : Current Reviews, 37(2), 223–236
Christopher Fink, Iordanes Karagiannides, Kyriaki Bakirtzi, Charalabos Pothoulakis; Adipose Tissue and Inflammatory Bowel Disease Pathogenesis, Inflammatory Bowel Diseases, Volume 18, Issue 8, 1 August 2012, Pages 1550–1557, https://doi.org/10.1002/ibd.22893
Freeman, H. J. (2008). Use of the Crohn’s disease activity index in clinical trials of biological agents. World Journal of Gastroenterology : WJG, 14(26), 4127–4130. http://doi.org/10.3748/wjg.14.4127
Furrie, E., Macfarlane, S., Kennedy, A., Cummings, J. H., Walsh, S. V., O’Neil, D. A., & Macfarlane, G. T. (2005). Synbiotic therapy (Bifidobacterium longum/Synergy 1) initiates resolution of inflammation in patients with active ulcerative colitis: a randomised controlled pilot trial. Gut, 54(2), 242–249. http://doi.org/10.1136/gut.2004.044834
Freeman, H. J. (2009). Long-term natural history of Crohn’s disease. World Journal of Gastroenterology : WJG, 15(11), 1315–1318. http://doi.org/10.3748/wjg.15.1315
Antonios Gklavas, Dionysios Dellaportas, Ioannis Papaconstantinou, Risk factors for postoperative recurrence of Crohn’s disease with emphasis on surgical predictors, 2017 DOI: 10.20524/aog.2017.0195 © 2017 Hellenic Society of Gastroenterology
Ghishan, F. K., & Kiela, P. R. (2014). Epithelial Transport in Inflammatory Bowel Diseases. Inflammatory Bowel Diseases, 20(6), 1099–1109. http://doi.org/10.1097/MIB.0000000000000029
Hovde, Ø., & Moum, B. A. (2012). Epidemiology and clinical course of Crohn’s disease: Results from observational studies. World Journal of Gastroenterology : WJG, 18(15), 1723–1731. http://doi.org/10.3748/wjg.v18.i15.1723
Jung, C., Hugot, J.-P., & Barreau, F. (2010). Peyer’s Patches: The Immune Sensors of the Intestine. International Journal of Inflammation, 2010, 823710. http://doi.org/10.4061/2010/823710
Kappelman, M. D., Moore, K. R., Allen, J. K., & Cook, S. F. (2013). Recent Trends in the Prevalence of Crohn’s Disease and Ulcerative Colitis in a Commercially Insured US Population. Digestive Diseases and Sciences, 58(2), 519–525. http://doi.org/10.1007/s10620-012-2371-5
Kim, D. H., & Cheon, J. H. (2017). Pathogenesis of Inflammatory Bowel Disease and Recent Advances in Biologic Therapies. Immune Network, 17(1), 25–40. http://doi.org/10.4110/in.2017.17.1.25
Kawaguchi, T., Mori, M., Saito, K., Suga, Y., Hashimoto, M., Sako, M., … Takazoe, M. (2015). Food antigen-induced immune responses in Crohn’s disease patients and experimental colitis mice. Journal of Gastroenterology, 50(4), 394–405. http://doi.org/10.1007/s00535-014-0981-8
Kennedy, P. J., Clarke, G., O‘Neill, A., Groeger, J. A., Quigley, E. M. M., Shanahan, F., … Dinan, T. G. (2014). Cognitive performance in irritable bowel syndrome: evidence of a stress-related impairment in visuospatial memory. Psychological Medicine, 44(7), 1553–1566. http://doi.org/10.1017/S0033291713002171
Khan, I., Samson, S. E., & Grover, A. K. (2017). Antioxidant Supplements and Gastrointestinal Diseases: A Critical Appraisal. Medical Principles and Practice, 26(3), 201–217. http://doi.org/10.1159/000468988
Lewis, J. D., Chen, E. Z., Baldassano, R. N., Otley, A. R., Griffiths, A. M., Lee, D., … Bushman, F. D. (2015). Inflammation, Antibiotics, and Diet as Environmental Stressors of the Gut Microbiome in Pediatric Crohn’s Disease. Cell Host & Microbe, 18(4), 489–500. http://doi.org/10.1016/j.chom.2015.09.008
Lee, D., Albenberg, L., Compher, C., Baldassano, R., Piccoli, D., Lewis, J. D., & Wu, G. D. (2015). Diet in the Pathogenesis and Treatment of Inflammatory Bowel Diseases. Gastroenterology, 148(6), 1087–1106. http://doi.org/10.1053/j.gastro.2015.01.007
Leonetti, D., Reimund, J.-M., Tesse, A., Viennot, S., Martinez, M. C., Bretagne, A.-L., & Andriantsitohaina, R. (2013). Circulating Microparticles from Crohn’s Disease Patients Cause Endothelial and Vascular Dysfunctions. PLoS ONE, 8(9), e73088. http://doi.org/10.1371/journal.pone.0073088
Li, Q., Wang, C., Tang, C., He, Q., Li, N., & Li, J. (2014). Dysbiosis of Gut Fungal Microbiota is Associated With Mucosal Inflammation in Crohn’s Disease. Journal of Clinical Gastroenterology, 48(6), 513–523. http://doi.org/10.1097/MCG.0000000000000035
Lewis, R. T., & Maron, D. J. (2010). Efficacy and Complications of Surgery for Crohn’s Disease. Gastroenterology & Hepatology, 6(9), 587–596.
Muniz, L. R., Knosp, C., & Yeretssian, G. (2012). Intestinal antimicrobial peptides during homeostasis, infection, and disease. Frontiers in Immunology, 3, 310. http://doi.org/10.3389/fimmu.2012.00310
Michielan, A., & D’Incà, R. (2015). Intestinal Permeability in Inflammatory Bowel Disease: Pathogenesis, Clinical Evaluation, and Therapy of Leaky Gut. Mediators of Inflammation, 2015, 628157. http://doi.org/10.1155/2015/628157
Nickerson, K. P., Chanin, R., & McDonald, C. (2015). Deregulation of intestinal anti-microbial defense by the dietary additive, maltodextrin. Gut Microbes, 6(1), 78–83. http://doi.org/10.1080/19490976.2015.1005477
Nikolaus S, Schulte B, Al-Massad N, Thieme F, Schulte D, Bethge J, Rehman A, Tran F, Aden K, Häsle R, Moll N, Schütze G, Schwarz M, Waetzig G, Rosenstiel P, Krawczak M, Szymczak S, Schreiber S, (2017) Increased Tryptophan Metabolism Is Associated With Activity of Inflammatory Bowel Diseases, Gastroenterology , Volume 153 , Issue 6 , 1504 – 1516.e2
Ng, S. C. (2016). Emerging Trends of Inflammatory Bowel Disease in Asia. Gastroenterology & Hepatology, 12(3), 193–196.
Nemeth, Z. H., Bogdanovski, D. A., Barratt-Stopper, P., Paglinco, S. R., Antonioli, L., & Rolandelli, R. H. (2017). Crohn’s Disease and Ulcerative Colitis Show Unique Cytokine Profiles. Cureus, 9(4), e1177. http://doi.org/10.7759/cureus.1177
Ott, C., Takses, A., Obermeier, F., Schnoy, E., & Müller, M. (2014). Smoking increases the risk of extraintestinal manifestations in Crohn’s disease. World Journal of Gastroenterology : WJG, 20(34), 12269–12276. http://doi.org/10.3748/wjg.v20.i34.12269
Y Ogura, S Lala, W Xin, E Smith, T A Dowds, F F Chen, E Zimmermann, M Tretiakova, J H Cho, J Hart, J K Greenson, S Keshav, G Nuñez (2003). Expression of NOD2 in Paneth cells: a possible link to Crohn’s ileitis. Gut, 52(11), 1591–1597.
Papa, A., Gerardi, V., Marzo, M., Felice, C., Rapaccini, G. L., & Gasbarrini, A. (2014). Venous thromboembolism in patients with inflammatory bowel disease: Focus on prevention and treatment. World Journal of Gastroenterology : WJG, 20(12), 3173–3179. http://doi.org/10.3748/wjg.v20.i12.3173
Peyrin‐Biroulet, L., Chamaillard, M., Gonzalez, F., Beclin, E., Decourcelle, C., Antunes, L., … Desreumaux, P. (2007). Mesenteric fat in Crohn’s disease: a pathogenetic hallmark or an innocent bystander? Gut, 56(4), 577–583. http://doi.org/10.1136/gut.2005.082925
Pascal, V., Pozuelo, M., Borruel, N., Casellas, F., Campos, D., Santiago, A., … Manichanh, C. (2017). A microbial signature for Crohn’s disease. Gut, 66(5), 813–822. http://doi.org/10.1136/gutjnl-2016-313235
Posovszky, C., Pfalzer, V., Lahr, G., Niess, J. H., Klaus, J., Mayer, B., … von Boyen, G. B. (2013). Age-of-onset-dependent influence of NOD2 gene variants on disease behaviour and treatment in Crohn’s disease. BMC Gastroenterology, 13, 77. http://doi.org/10.1186/1471-230X-13-77
Rogler, Gerhard; Zeitz, Jonas; Biedermann, Luc (2016). The search for causative environmental factors in inflammatory bowel disease. Digestive Diseases, 34(Suppl 1):48-55.
Rahman, K., Sasaki, M., Nusrat, A., & Klapproth, J.-M. A. (2014). Crohn’s disease-associated Escherichia coli survive in macrophages by suppressing NFκB signaling. Inflammatory Bowel Diseases, 20(8), 1419–1425. http://doi.org/10.1097/MIB.0000000000000096
Ryan, J. L., Shen, Y.-J., Morgan, D. R., Thorne, L. B., Kenney, S. C., Dominguez, R. L., & Gulley, M. L. (2012). Epstein-Barr Virus Infection is Common in Inflamed Gastrointestinal Mucosa. Digestive Diseases and Sciences, 57(7), 1887–1898. http://doi.org/10.1007/s10620-012-2116-5
Rivière A, Selak M, Lantin D, Leroy F and De Vuyst L (2016) Bifidobacteria and Butyrate-Producing Colon Bacteria: Importance and Strategies for Their Stimulation in the Human Gut. Front. Microbiol. 7:979. doi: 10.3389/fmicb.2016.00979
Ruemmele F, M, Role of Diet in Inflammatory Bowel Disease. Ann Nutr Metab 2016;68(suppl 1):32-41 https://doi.org/10.1159/000445392
H. H. Rasmussen, J. F. Fallingborg, P. B. Mortensen, M. Vyberg, U. Tage-Jensen & S. N. Rasmussen (1997) Hepatobiliary Dysfunction and Primary Sclerosing Cholangitis in Patients with Crohn’s Disease, Scandinavian Journal of Gastroenterology,32:6, 604-610, DOI: 10.3109/00365529709025107
Salkic, N. N., Adler, G., Zawada, I., Alibegovic, E., Karakiewicz, B., Kozlowska-Wiechowska, A., … Bielicki, D. (2015). NOD2/CARD15 mutations in Polish and Bosnian populations with and without Crohn’s disease: prevalence and genotype-phenotype analysis. Bosnian Journal of Basic Medical Sciences, 15(2), 67–72. http://doi.org/10.17305/bjbms.2015.348
Segal AW. Making sense of the cause of Crohn’s – a new look at an old disease [version 1; referees: 1 approved, 1 approved with reservations]. F1000Research2016, 5:2510
Spekhorst, L. M., Visschedijk, M. C., Alberts, R., Festen, E. A., van der Wouden, E.-J., Dijkstra, G., … Dutch Initiative on Crohn and Colitis (ICC). (2014). Performance of the Montreal classification for inflammatory bowel diseases. World Journal of Gastroenterology : WJG, 20(41), 15374–15381. http://doi.org/10.3748/wjg.v20.i41.15374
Alan Siroy, Jay Wasman, (2012) Metastatic Crohn Disease: A Rare Cutaneous Entity. Archives of Pathology & Laboratory Medicine: March 2012, Vol. 136, No. 3, pp. 329-332. https://doi.org/10.5858/arpa.2010-0666-RS
Saez-Lara, M. J., Gomez-Llorente, C., Plaza-Diaz, J., & Gil, A. (2015). The Role of Probiotic Lactic Acid Bacteria and Bifidobacteria in the Prevention and Treatment of Inflammatory Bowel Disease and Other Related Diseases: A Systematic Review of Randomized Human Clinical Trials. BioMed Research International, 2015, 505878. http://doi.org/10.1155/2015/505878
Shi, N., Li, N., Duan, X., & Niu, H. (2017). Interaction between the gut microbiome and mucosal immune system. Military Medical Research, 4, 14. http://doi.org/10.1186/s40779-017-0122-9
Steed, H. , Macfarlane, G. T., Blackett, K. L., Bahrami, B. , Reynolds, N. , Walsh, S. V., Cummings, J. H. and Macfarlane, S. (2010), Clinical trial: the microbiological and immunological effects of synbiotic consumption – a randomized double‐blind placebo‐controlled study in active Crohn’s disease. Alimentary Pharmacology & Therapeutics, 32: 872-883. doi:10.1111/j.1365-2036.2010.04417.x
Shelley-Fraser, G., Borley, N. R., Warren, B. F., & Shepherd, N. A. (2012). The connective tissue changes of Crohn’s disease. Histopathology, 60(7), 1034-1044. doi:10.1111/j.1365-2559.2011.03911.x
SOBRADO, Carlos Walter, LEAL, Raquel Franco, & SOBRADO, Lucas Faraco. (2016). THERAPIES FOR CROHN’S DISEASE: a clinical update. Arquivos de Gastroenterologia, 53(3), 206-211. https://dx.doi.org/10.1590/S0004-28032016000300016
Severine Vermeire,Stefan Schreiber, William J. Sandborn, Cécile Dubois, Paul Rutgeerts, Correlation Between the Crohn’s Disease Activity and Harvey–Bradshaw Indices in Assessing Crohn’s Disease Severity Clinical Gastroenterology and Hepatology , Volume 8 , Issue 4 , 357 – 363 DOI: https://doi.org/10.1016/j.cgh.2010.01.001
Wexler, H. M. (2007). Bacteroides: the Good, the Bad, and the Nitty-Gritty. Clinical Microbiology Reviews, 20(4), 593–621. http://doi.org/10.1128/CMR.00008-07
Wilson, M., Seymour, R., & Henderson, B. (1998). Bacterial Perturbation of Cytokine Networks. Infection and Immunity, 66(6), 2401–2409.
Zhang, Y.-J., Li, S., Gan, R.-Y., Zhou, T., Xu, D.-P., & Li, H.-B. (2015). Impacts of Gut Bacteria on Human Health and Diseases. International Journal of Molecular Sciences, 16(4), 7493–7519. http://doi.org/10.3390/ijms16047493
Content retrieved from: https://amyrnielsen.wordpress.com/blog/.