Probiotics and Crohn's

Probiotics* are wildly popular right now, and certainly an advertising boon for the food and nutritional industries.  For example, I was just at my local Whole Foods and happened to notice the very conspicuous, colorful “Probiotics” sign over the yogurt case… I don’t even remember there being an equivalent sign indicating what they were actually selling, i.e. “Yogurt” (for the record, I am a frequent consumer of Whole Foods yogurt because I think it’s delicious).  Research seems to suggest that gut bacteria are undoubtedly important for health and wellbeing, and the extent to which they interact with and regulate human physiology is only starting to be understood.  This is a really exciting current field of research, known as the Human Microbiome Project (HMP), which is a multiinstuitional consortium (i.e. large group of researchers across the country) funded by the National Institutes of Health* (NIH) focused on understanding all of the places where bacteria live in us, all of the types of bugs, and how they impact our lives.  However, there is less clear evidence at this point of the direct health benefits of probiotics… in general and for inflammatory bowel disease (IBD), including Crohn's.

Before I launch into the specific scientific investigations with this blog post, I want to highlight my general theme with a transcription from NPR’s Science Friday, which I find particularly illustrative on the state of gut bacterial research.  This was taken from an interview with Dr. Jeffery Gordon, one of the leaders of the HMP (and I am happy to say is on the faculty Washington University in St. Louis... where I am in training), who has published work on the impact of yogurt bacteria on the gut microbiome.

John Dankosky: Jeffrey Gordon, do you eat yogurt every day?

Dr. Jeffery Gordon: I don't eat a yogurt every day, but I do eat yogurt intermittently.

John Dankosky: OK, and it has any health benefits for you?

Dr. Jeffery Gordon: Um, not noticable, but I enjoy the experience.

The bottom line is basically that gut bacteria do matter, but we don't really understand their importance yet.  So go ahead and enjoy your yogurt because it is a tasty, nutritious snack, but don't expect it to cure what ails you... for now at least.

Microbes in the normal human gut

Due to research conducted largely through the HMP, and with the help of generous "specimen" donations from study participants, we now have a great deal of knowledge about the bacterial composition of the human gastrointestinal (GI) tract.  The colonization of the gut starts after birth, when our initially sterile (germ free) GI systems become progressively populated with a dense bacterial community.  There are thought to be approximately 100 trillion bacteria in the average human gut, many of which live in the colon, and hundreds of different bacterial species make up this complex ecosystem (Jonkers et al. 2012).

So, some of you out there may be wondering why we have all of these bugs living within us, especially given that we generally associate bacteria with infection and disease.  It is somewhat counterintuitive to our knowledge that these bacteria are actually beneficial for us, and we have developed a symbiotic relationship (i.e. coexistence in which both organisms benefit) by hosting their residence in our GI tracts.  Microbes in the gut seem to be particularly important for the development of the normal immune system response of the GI tract, which is crucial for our health given that we encounter many pathogens in the gut after eating them (Jonkers et al. 2012).  In addition, colonization by "good" bacteria may actually help defend against pathogens.

Gut microbial alterations in Crohn's patients

I mentioned in my previous Crohn's 101 blog post that there is evidence that microbes in the gut are involved  in producing the overaggressive inflammation of IBD.  There is also research suggesting that the types of bacteria residing in the intestines of Crohn's patients are different from and less diverse than in individuals without the disease (Jonkers et al. 2012).  And, despite that there are fewer types of bacteria comprising the gut microbiome in patients with IBD, the overall counts of bacteria seem to be higher when compared with normal individuals.  There also may be a relationship between bacterial counts and IBD activity, with greater counts in active disease, but this has not been confirmed in all studies.

Probiotics as therapy for Crohn's?

It is estimated that up to 50% of patients with IBD have attempted to use probiotics for their disease, either at the recommendation of a physician or as self-prescribed alternative therapy (Mack. 2011)... and I myself fall into this ~50%.  But does the research support that probiotics are actually beneficial for Crohn's disease?  Digging into the studies that have evaluated probiotics as a therapy for Crohn's, the conclusions at the moment are similar to those for probiotic use in general... currently there seems to be no clear benefit of probiotics for induction or maintenance of remission, or for the management of post-operative Crohn's disease (Jonkers et al. 2012.; Mack. 2011).  Many of the studies have evaluated the potential effects of probiotics in several different ways... with endoscopic activity, serologic markers (i.e. blood tests such as for C-reactive protein*), and/or Crohn's disease activity scores.  There were several different types of bacteria tested individually in many of these studies, but only a couple of the investigations attempted using several strains of bugs mixed together at the same time.  Despite these somewhat disappointing results thus far, it does seem that there hasn't been enough research into the matter, and the reported studies have only involved relatively small numbers of patients... meaning that small benefits (or harms) of probiotic therapy would be difficult to detect.

So what do we know that probiotics actually do?

For the answer to this question, I actually return to research conducted by the laboratory of Dr. Jeffery Gordon.  In one study, they sampled GI bacterial content of genetically identical twins, and then had the twins start eating  a commercially available yogurt with live, active cultures for a certain window of time (McNulty et al. 2011).  Then the twins were instructed to stop eating the yogurt. Surprisingly, they found that the consumption of the probiotic bacteria in yogurt did not alter the normal gut bacterial communities.  But this doesn't mean the probiotic bacteria didn't have an important effect... the changes that did happen as a result of yogurt consumption were actually in how the colonizing bacteria processed certain types of nutrients.  Basically, the strains of bacteria in the yogurt were able to somehow communicate with the normal gut microbes, telling the gut bacteria to alter their own digestion of other products that we consume (yes, the bacteria in our gut break down a lot of the things in our food that we don't digest).  In particular, these probiotics improved how our resident microbes processed polysaccharides (a type of carbohydrate), and, thus, the products of polysaccharide break down could be more available to the human host.  However, the implications of this finding seem unclear at the moment.

Concluding thoughts

While there isn't evidence to support the use of probiotics for Crohn's therapy, there isn't evidence of harm from their consumption either.  So, if you are going to enjoy that yogurt anyway, and you accept that there may or may not be some benefit to your gut... then go ahead and have those probiotics.  However, it's probably not worth paying an extra $25 (or whatever) for that bottle of pure, encapsulated bacilli based on what we currently know.  But, in general, I don't think the research community has definitively answered the question yet of whether certain kinds of supplemental bacteria could be beneficial for general health and/or Crohn's disease, so it will be worth keeping an eye on further developments in this arena.

Bibliography:

Jonkers et al. (2012) Probiotics in the Management of Inflammatory Bowel Disease; A Systematic Review of Intervention Studies in Adult Patients. Drugs 72:803-823.

Mack. (2011) Probiotics in Inflammatory Bowel Diseases and Associated Conditions. Nutrients 3:245-264.

McNulty et al. (2011) The Impact of a Consortium of Fermented Milk Strains on the Gut Microbiome of Gnotobiotic Mice and Monozygotic Twins. Science Translational Medicine 3:106ra106.

*A few specific terminology explanations:

C-reactive protein (CRP): This is a protein that is made in the liver in response to inflammation and then gets released into and circulates within the blood.  Because CRP levels are elevated during inflammation, the concentration can be measured as a test for active Crohn's disease.  But this test is not specific for Crohn's disease activity, because CRP can be made in response to other kinds of inflammation, including infection or cardiovascular disease.  Also, it's worth noting that some patients can still have active Crohn's disease (confirmed endoscopic inflammation) with normal CRP levels.

National Institutes of Health (NIH): The NIH is an agency of the US Department of Health and Human Services that is responsible for directing and funding biomedical research in the US.  The NIH has an Intramural Research Program, in which research is conducted at the "headquarters" in Bethesda, Maryland, and an Extramural Research Program, which funds research at many academic and medical institutions across the country.  There are 27 different sub-institutes of the NIH, each with their own focus in biomedical research, such as cancer, cardiovascular disease, or aging.

Probiotics: This term essentially refers to microorganisms that are thought to be beneficial to the host in which they live.  These microorganisms are most commonly certain types of "good" bacteria, but there are also types of probiotic yeast.  Probiotics are usually administered (or consumed) as a component of fermented foods, such as yogurt, but can also be packaged as nutritional supplements.