This is quick post alerting my readers to some new research about Crohn’s disease (CD). CD is an inflammatory, autoimmune bowel disease that can affect any part of the digestive tract. However, it is most likely to manifest itself in the ileum of the small intestine or proximal colon. It primarily causes abdominal pain, diarrhea (bloody when inflammation is at its worst) and vomiting. It is often a cause of malabsorption of food leading to growth and/or nutrient deficiencies.
The disease is named after gastroenterologist Burrill Bernard Crohn, who in 1932 described the condition in patients he saw at Mount Sinai Hospital in New York City. CD can strike at any age, but is most commonly seen in those in their 20s and 30s.
In North America, prevalence has been estimated at between 400,000 to 600,000 people. The incidence in Europe is thought to be about a million.
While no one knows for sure why Crohn’s develops, research has revealed that sufferers mount an inappropriate response to gut flora. Some have speculated that this process is mediated primarily by genetic susceptibility (1), while others highlight environmental factors leading to a less diverse gut flora. (2)
One study noted the presence of immune antigens to various components of intestinal microorganisms. (3) Other studies have noted genetic abnormalities in the innate immune response to these same intestinal bacteria. (4) (5)
In a retrospective cohort study conducted in England that followed over one million children, those who received antibiotics during the first year of life were over five times more likely to develop an inflammatory bowel disease (IBD) like CD than children who hadn’t. (6)
Furthermore, each additional course of antibiotics was associated with a 6% increase in developing IBD. The risk decreased when first courses of antibiotics were administered at a later age. Antibiotics most associated with the development of IBD were the penicillins, broad-spectrum penicillins like Ampicillin, cephalosporins like Keflex, metronidazoles like Flagyl and fluoroquinolones like Cipro.
The role of disturbed intestinal flora in CD is also reflected by reduced bacterial diversity, especially the marked depletion of Bacteroidetes and Lachnospiraceae. (7) CD patients also commonly experience wide fluctuations in microbial populations during relapse.
Other potential culprits involve Escherichia coli (E. coli), Chlamydia pneumoniae and Mycobacterium avium subspecies paratuberculosis. (8) E. coli colinization of the gut wall has been shown to be more prevalent in those with Crohn’s in contrast to healthy controls. (9) (10)
What has always struck me as curious about patients suffering from both Crohn’s disease and ulcerative colitis is the common finding of an elevation in a particular cytokine known as interleukin-17 (IL-17). As a refresher, cytokines are immune signaling molecules. Consider them the hormones of the immune system, released in response to invasive threats to help coordinate an appropriate response.
IL-17 is secreted by Th17 cells mainly to fight fungal infections. Dendritic cells are a specialized type of white blood cell that are classified as antigen-presenting cells necessary for immune T cell activation. If these dendritic cells are stationed in an area of the body undergoing an infestation of yeast, they travel to nearby lymph nodes and activate T cells, which recognize the fungal antigens these cells are displaying.
These migrating dendritic cells produce transforming growth factor beta (TGFB) and interleukin 6 (IL-6), two other cytokines, which together influence other newly activated helper T cells to produce the Th17 subset. Apart from IL-17, interleukin 21 (IL-21) is also secreted. IL-21, in turn, serves as a growth factor for Th17 cells thus amplifying their immune effects.
IL-17 results in a massive recruitment of neutrophils, another type of white blood cell, to help destroy the fungal overgrowth. What has recently been learned is that persons who have an immune defect in regards to Th17 cells are particularly prone to suffer from recurring fungal infestations even though the rest of their immune system functions properly.
The role of fungal overgrowth in Crohn’s is becoming clearer. Antibodies against the yeast Saccharomyces cerevisiae have been found in 60% to 70% of CD patients. (11) (12). Saccharomyces cerevisiae, by the way, is common brewer’s or Baker’s yeast that is used to make bread and ferment wine or beer. Its presence, however, is not due to ingesting this yeast in food or beverages (yeast that is cooked or fermented is no longer active).
Rather, Saccharomyces cerevisiae is produced in response to colonization by the yeast Candida albicans (C. albicans). (13) C. albicans is a normal constituent of the human gastrointestinal tract. You were born with it and you will die with it. There is no such thing as eradicating it, nor should we if we could.
Like most organisms that exist in our gut, we have no real understanding how its presence affects our health. Looked at singly, potential pathogens that overgrow and displace beneficial bacteria within the digestive tract are harmful, however, when contained and controlled as part of a large and diverse ecosystem, their contribution is either neutral or possibly beneficial in ways that have yet to be discovered.
C. albicans overgrowth is common in the immune compromised such as those suffering from AIDS. It is also extremely common in people who abuse alcohol either chronically as in alcoholism, or acutely via binge drinking. Chronically elevated cortisol levels–as a consequence of emotional stress, corticosteroid use, alcohol abuse and gut dysbiosis–would of course depress immune function and open the door to uncontrolled yeast growth.
Many people who undergo extended or repeated courses of antibiotics often find to their dismay that once the bacterial infection has been conquered they are faced with a more tenacious foe in the form of recurrent fungal infections. For that reason, I have found it exceedingly rare that disordered gut flora is not simultaneously accompanied by yeast overgrowth and logically so.
The only thing keeping any potential gastrointestinal trouble maker at bay is healthy colonies of beneficial gut flora. Devastate those communities, and like night follows day, C. albicans growth is sure to follow. How bad the fungal overgrowth gets will depend on the functioning of the individual’s immune system and how depleted beneficial gut flora populations have become.
In mice, Candida albicans has been shown to induce inflammatory bowel disease. (14) CD sufferers are also more likely to suffer from Candida overgrowth than healthy controls. (15) In fact, not only have Crohn’s disease patients been found to be more frequently and heavily colonized by C. albicans, so too their non-CD relatives. Whether this finding is due to genetic predisposition, or the common finding that relatives and house mates often share similar gut flora populations, is still unclear.
The existence of high levels of anti-S. cerevisiae antibodies has been recognized as a useful indicator distinguishing CD from ulcerative colitis (UC). But ASCA are not the only antibodies found in CD patients.
The cell wall of C. albicans is quite complex being composed of various glycans. Glycans are polysaccharides or oligosaccharides, which are chains of sugar molecules strung together.
While ASCA are formed in response to the presence of mannan glycans in C. albicans, another class of antibodies, anti-lamimnaribioside (ALCA), is formed in response to a glycan of C. albicans known as glucan. Finally, anti-chitobioside antibodies (ACCA) are formed in response to chitin found in the cellular wall of this same yeast. Both ALCA and ACCA are also commonly found in CD sufferers.
These findings, therefore, point to a three-pronged strategy for combating Crohn’s: a) the use of short-course antibiotics to curb commonly found gut pathogens like E. coli, b) anti-fungals to reduce Candida overgrowth, and c) the use of both probiotics and prebiotics to encourage the growth of commensal organisms in both the small and large intestine.
In those cases where TH17 dysfunction is genetically mediated, life-long anti-fungal therapy may be a necessity along with ongoing probiotic/prebiotic supplementation. From a functional food standpoint, the daily consumption of raw garlic, an herb noted for both its antibacterial and anti-fungal properties as described here, may also help control this disorder.