a role for pattern-recognition receptors in gut flora dysbiosis in Crohn's

It's not been a spectacular last few days, and I've not been feeling particularly well.  The stress of my rotting teeth/jaw, decaying scalp, deteriorating wallet, work transitioning and the realization that in three months I will be leaving all the people I love is, indeed, catching up with me.

So I decided to make all efforts to allow today to be as awesome as possible... excluding exercising.  I'm at work at 6am, which is early for me these days, in order to finish a project before 1pm... so that I can make it to my fourth dental appointment in the last three weeks... so that I can receive some more bad news... so that I can be sucked down into the gutter and then be plucked out again by a dinner with two of my favorite human beings tonight.

I've been reading a lot of literature on the imbalance of helpful and harmful gut flora lately, a condition called dysbiosis.  There have been several microbiota implicated in Crohn's disease (klebsiella, E. coli, paratuberculosis, Campylobacter jejuni, enterohepatic Helicobacter species).  However, a recent review in Nature suggests that no single bacterium has been definitively associated with Crohn's.  Instead, Si Ming Man and colleagues argue that defective sensing, killing off and generally balancing of gut microbiota is largely due to defective pattern-recognition receptors.


Pattern-recognition receptors are just what they sound like. They allow the host [read: intestine] to identify molecular fluctuations in gut microbiota that might indicate harm, and activate an immune response.  These pattern-recognition receptors (mostly toll-like receptors) in membranes of the epithelial cells that line the gut activate nuclear factor kB (NFkB), which leads to productions of interleukins and the infamous TNFalpha.



Man SM, Kaakoush NO, & Mitchell HM (2011). The role of bacteria and pattern-recognition receptors in Crohn's disease. Nature reviews. Gastroenterology & hepatology, 8 (3), 152-68 PMID: 21304476

some more great research into the role of gut flora in digestive disease

A recent article in Scientific American left me surprisingly impressed with its coverage of some very well done research presented by post doctoral fellow Michelle Smith at the International Human Microbiome Congress in Vancouver, Canada.  Kwashiorkor is the condition that causes the abdominal swelling due to malnutrition that is so common in poverty- and famine-stricken regions.  Smith concluded that differences in gut flora can determine individual susceptibility to malnutrition and other illnesses.

This kind of research bodes well for the acceptance of balancing gut flora as an approach to treating many gastrointestinal disorders.

the "no more pain until this remicade shit kicks in" diet

No matter how much research I do, my mother will always be smarter than me.

She will always be better at taking care of me when I'm sick than I am.  H.B. is new at all this, but someday he will be better at it than I am, too.  Mom is close enough to it to know the personal urgency, and far enough removed from it to consider what I have moved on from and forgotten is important.

The Short Term, for instance.  I've been so enthused about finding new ways to make vegetables more benign that I've forgotten that if I'm still having pain, they're probably not a good idea at all, even cooked and pureed.  In the long term, the SCD-esque diet will probably be quite helpful in maintaining whatever level of pain-free I can achieve with the Remicade.  But I have not gotten there yet -- clearly.  In the short term, I have to allow myself to eat grains and starches: although they're probably feeding whatever gut flora are overgrown and causing problems, they remain the only food stuff that (unless consumed in large quantities) goes down with little to no pain.  At this point in time, the goal is to avoid  pain.  Balancing diet to maintain that state has to come later.  Horse before the cart, etc.

I've always had trouble with fresh fruits and vegetables; whether it's Oral Allergy Syndrome or Crohn's, it's an inflammatory reaction, which, if it's happening in my mouth and esophagus is probably also happening in my intestine.  Since I don't have a spy down there, and my doctors seem to think my scans are "clean", I can't know for sure, but I would postulate that since my left large intestine and mid-lower small bowel throw temper tantrums whenever meals reach them, there has to be either a bigger stricture problem than Dr. P and Dr. S could see, or an inflammatory reaction to the food itself.  Deductive reasoning says one of these things must be occurring.  Good thing I have an amazing doctor to help me figure out which so I can make it go away faster... oh, wait...

My mom and dad are also the only people other than myself who have been doing this as long as I have.  Granted, they haven't lived with me for some time, but they remain my health care consultants and medical advocates in times of need (which lately is fairly often, especially if I'm in drug-delusion mode).  They remember details from the Original flares from over a decade ago... I'll be damned if I can remember flares that accurately from when I was that young.  Pain has a unique way of making my brain cease to function.  I also have a sneaking suspicion that details stick in your mind better when you're trying to keep your child from suffering.

Veggies are too new yet -- even cooked -- to strain in my belly, it seems.  Given the ridiculous flares of the past three days, it was too soon to kick out so many carbohydrates from my diet; I need them to cushion whatever else I'm putting in (which at the moment is some variation of Boost, applesauce and sushi -- yeah, small quantities of raw fish are also harmless, go figure).  So, in my mother's honor, I'm admitting defeat and stepping back to the "no pain until this Remicade shit kicks in" diet.

Tofu, Squash and the Microbial Squadron

In the quest to ween off of the short-term friendly diet base of breads and rice, I am finding two things:

1) My allergies dictate that a myriad of exceptions from the rules be formulated, and

2) These diets -- particularly the ones that are based on moving away from modern food-preservation and agricultural technology -- are far too nit-picky for my stress level.  That is fantastic for people who can and/or need to be that scrupulous with what they put into their bodies (often Coeliacs and Rheumatoid Arthritics, both malabsorption-centric), but not for me.

Current quests: 

1) to replace most rice noodles with various stringed squashes, and

2) replace most breads with tofu.

Current obstacles:

1) If my SBFT results come back rampant with strictures, I will not be able to eat stringed squash, and

2) tofu is "illegal" on the SCD diet (my guiding reference).

Current absurdities:

1)   Spaghetti squash is high in complex carbohydrates.  Why is it on the SCD diet if this is so?  Because these complex carbohydrates are not starches (2), the favorite sustenance of the microbial squadron.  Therefore, spaghetti squash is excellent for the SCD diet, but not so excellent for me... in terms of making it through my system, rice noodles are better.  Sacrifice the carbohydrate eradication or risk intestinal rupture?  This is going to involve a very slow process of replacing carbs with fiber one food at a time; elsewise, my poor brain will not be able to suppress the hormonal onslaught of PPR-bred anxiety.

2) The reason that tofu is illegal on the SCD diet is because of the ambivalence of its carbohydrate content.  Apparently, no one has bothered to figure out what carbohydrate prevalence results from the fermentation and processing of the genetically manipulated soy beans that beget tofu.  My condition at the moment is more defined by "solid substance sensitivity" than by my concern for entirely starving out the microbial forces in my gut (see above).  Therefore, the carbohydrate content of tofu being so minimal as compared to its protein and fiber content -- even as its carbohydrate chain specificities are unknown -- I will allow it.  I simply can't afford to eliminate everything by-the-molecule, only to reduce.  Baby steps.

Additionally, screw complete elimination of rice because if I cannot eat sushi once in a while life is just not worth the hassle.

Of Sushi, Star Trek and Klebsiella

Enough of these Crohn's disease-linked genes!  I found this phenomenal post the other day from Dr. Ayers at the College of Idaho on a link between a particular flora and Crohn's disease.  Klebsiella pneumoniae is a bacteria that colonizes in the healthy mouth, lungs and intestines.  Dr. Ayers writes about the excess of this bacteria in the intestines of Crohn's disease patients.  Its role in Crohn's patients, he suggests, may be related to its ability to produce hydrogen gas, on which the notorious H. pylori feeds.  Here is the bridge:  carbohydrates feed Klebsiella, which produces the hydrogen gas that feeds H. pylori, which then destroys the mucosal and epithelial lining of the stomach and upper intestines...

Intrigued, I of course had to hunt down the primary literature of these claims (tsk tsk, Professor Ayers!).  Below is a compilation of my favorite excerpts; this is a beautifully put together review paper by Rashid et al 2009.

"Klebsiella microbes have been isolated from the large bowel biopsy specimens in more than 25% of patients with CD or UC [42], and relapses in patients with CD were found to be associated with Klebsiella intestinal infections [43]. In a study using immunohistochemistry, however, it has been observed that the majority of patients with IBD had negative staining
specimens for E. coli, L. monocytogenes and K. pneumoniae taken from the bowel mucosa [44]. These latter findings indicate that it is the microbial bulk in the intestinal lumen rather than at the sites of the pathological lesions, which is important in evoking both local mucosal and general antibacterial immune responses.

"Elevated levels of antiKlebsiella antibodies have been reported in patients with CD from six different centres in the UK (Table 2). Significantly elevated levels of antibodies against K. pneumoniae and Y. enterocolitica microbial agents were observed in patients with CD and UC when compared with healthy controls [48]. Similar findings were later shown by other groups from Scotland, where IgA antibody levels against K. pneumoniae were found to be elevated in patients with AS and IBD [49,50].

 "Klebsiella microbes possess a powerful debranching enzyme, pullulanase, which is a molecular complex consisting of 17 components and some of these exhibit molecular mimicry with several collagens. pulA cross-reacts with collagens I, III and IV [46]... Significantly elevated levels of antibodies against Klebsiella microbes as well as autoantibodies to collagens I, III and IV were observed in patients with AS and CD [55].

"The hypothesis proposed is that exposure to the cross-reactive antigens of pulA found in Klebsiella pullulanase leads to the production of autoantibodies that can have a pathological effect on the collagens found in the intestinal mucosa and eventually lead to the characteristic lesions of established CD (Fig. 2).

"In a study carried out by a group from Los Angeles, it was observed that the mean number of faecal Klebsiella microorganisms in individuals taking high-carbohydrate/ low-protein diet was 40 times higher than in those individuals receiving low-carbohydrate/high-protein diet [69]. In a comparative study, it has been observed that the mean number of Klebsiella was 10 times higher for simple sugars per gram of substrate compared with the value obtained after incubation with 11 different amino acids [70].

"A clear link is observed between increased intake of starch and the bulk of intestinal microflora, among which Klebsiella microbes constitute an important part. High dietary starch intake leads to increased growth of these microbes in the bowel."

 But what about the provision of hydrogen gas to H. pylori by an intestinal Klebsiella bloom?

Crohn's patients have a heightened immuno-sensitivity to Klebsiella microflora (Rashid et al 2009).
Klebsiella yields a high molar ratio of hydrogen per starch (Chen et al 2005).
Hydrogen gas feeds H. pylori (Olson et al 2004).
Klebsiella feeds on starches, mono- and disaccharides (Rashid et al 2009).
Ergo: starve out the Klebsiella with a low starch/carbohydrate diet, and in doing so, starve out the H. pylori.  Lowering your H. pylori levels, if this particular bacterium is a prominent contributor to your Crohn's, IBS or Colitis, may substantially alleviate a great deal of epithelial destruction, and suppress the inflammatory response.  I like it.  Go, science!

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In other, more important news, last night was homemade sushi and Star Trek night.  Tuna, crab, Tofutti BTCC, avocado, Insurrection.  There are just too few relaxing evenings that even come close to challenging that.