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Crohns - Caused by an Unhealthy Gut or Causing the Unhealthy Gut?

Some experts believe that the secret to overcoming Crohn’s disease is a healthy gut. Increasingly, this conclusion is confirmed by new studies. These studies also show that Crohn’s disease has its roots in pathogenic microbes that colonize the gut and that the disease can be put in remission by replacing the lost gut flora with probiotics. What are probiotics? Are they safe, are they effective? Why are there mixed results from clinical trials investigating their benefits in Crohn’s disease? This article provides a thorough understanding of the role of probiotics in Crohn’s disease.
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Bacteria and Crohn’s Disease

Although Crohn’s disease was once believed to be an autoimmune disease, recent studies have established that it is really caused by impaired innate immunity.

The impairment in the immune system affects the body’s ability to clear bacteria from intestinal walls. This weakens the intestinal mucosa and allows microbes to proliferate and cause further damage.

Studies also show that impairment of innate immunity and susceptibility to intestinal pathogen also have genetic components. For example, mutations in the NOD2 gene have been shown to directly affect the activities of macrophages.

This leads to the impairment of the innate immunity as well as adaptive immunity.

Bacteria associated with Crohn’s disease include Mycobacterium avium subspecies paratuberculosis and a strain of Escherichia coli that has a high affinity for hiding from immune cells. Candida albicans, a fungus, is also closely linked with Crohn’s disease.

The named Mycobacterium species releases a group of compounds called mannins. These allow it to resist destruction by phagocytes (immune cells known to engulf and destroy microbes). These compounds can also protect other bacteria in the gut.

Resistant and invasive E. coli, on the other hand, hides in phagocytes to form macrophages. From there, it releases inflammatory cytokines such as TNF-alpha (tissue necrosis factor-alpha).

In summary, the invasion of the gut by bacterial pathogens, such as the two discussed above, is responsible for the perpetuation of Crohn’s disease and the worsening of symptoms.

What Are Probiotics?

Probiotics are live, safe microbes that can improve the health of the host or carrier.

Perhaps the most common example of probiotics in human nutrition is the starter culture added to fermented dairy products such as yogurt.

The two most commonly used bacteria in probiotic preparations are bifidobacteria and lactic acid bacteria. Other bacteria in the bacillus family are commonly used as well as certain yeasts.

More often than not, probiotics are used to improve gastrointestinal bacterial flora.

This means that they are introduced to the gut to outcompete pathogens. By competing with harmful bacteria in the gut, they can reduce the population of these pathogens and, therefore, prevent them from damaging the intestinal mucosa.

Unlike probiotics, antibiotics do not differentiate between harmful and beneficial bacteria. Therefore, prolonged antibiotic therapy can wipe out the population of beneficial bacteria in the gut. This may cause diarrhea and other forms of opportunistic infections in different parts of the gastrointestinal tract.

In such cases, probiotics are usually given to restore the population of beneficial bacteria in the gut and to stop the overgrowth of pathogens.

Although probiotics can be effective in the treatment of certain acute and chronic diseases especially those involving the gastrointestinal tract, they are not without their side effects.

Probiotics can be harmful when given to those who are critically ill. This is because a weakened immune system may leave the body susceptible to even symbiotic microbes such as probiotics. In addition, at least one study indicate that probiotics may increase the risk of developing sensitivity to allergens in children.

Probiotics and Crohn’s Disease

Probiotics may help relieve the symptoms of Crohn’s disease. Although they should not be relied on solely, they can reduce symptoms enough to put the disease in remission.

Probiotics are especially effective for patients who have been placed on long-term steroid and/or antibiotic therapies. This is because such drugs can destroy the delicate bacterial flora in the gut. In such cases, probiotics will restore beneficial bacteria in the gut while reducing the damage of pathogens.

Discussed below are the different ways probiotics can help patients with Crohn’s disease.

Diarrhea

Studies show that probiotics can reduce the incidence and severity of diarrhea as well as the frequency of stools in patients with Crohn’s disease.

Probiotics are most relevant in Crohn’s disease when the diarrhea is caused by antibiotic therapy.

Because antibiotics change the population of bacteria growing in the gut, it can cause diarrhea

  • by promoting the opportunistic growth of pathogenic microbes. When microbes such as Clostridium difficile colonize the gastrointestinal tract, they can directly cause diarrhea.
  • by affecting the metabolism of carbohydrates and reducing the absorption of fatty acids. These changes increase osmotic pressure in the gut and directly leads to diarrhea.

Therefore, probiotics are recommended for patients with Crohn’s disease who are placed on antibiotics.

However, the strain of probiotic given and the dose in which it is administered will determine the effectiveness of the anti-diarrheal therapy. Probiotic formulations with Lactobacillus rhamnosus have been found effective in different trials.

Overall, probiotics are known to reduce the occurrence of antibiotics-induced diarrhea by 50%.

Lactose Intolerance

Lactose intolerance is more common among patients with Crohn’s disease than in the general population.

However, certain strains of probiotics can help patients who also suffer from lactose intolerance to tolerate lactose better. This is because some of these beneficial bacteria (the Lactobacillus species, for example) can efficiently break down lactose.

Therefore, probiotics can help patients with Crohn’s disease avoid the symptoms of lactose intolerance.

Colon Cancer

Colon cancer is a known complication of inflammatory bowel disease and patients with Crohn’s disease have an increased risk of this cancer especially if the damage to the intestinal tract is located in the colon.

The probiotic, Lactobacillus delbrueckii subsp. bulgaricus, has been shown to have anti-cancer properties because it binds to food carcinogens such as heterocyclic amines.

Animal studies confirm that this bacteria can indeed reduce the risk of colon cancer. However, human trials are still in the early stages.

Already, there are indications that certain probiotics exert anti-cancer effects by inhibiting the enzyme, beta glucuronidase. This enzyme is known to release carcinogens in the gastrointestinal tract. Therefore, probiotics can significantly protect the intestinal mucosa against free radical damage.

Immune Functions

Now that Crohn’s disease has been proven to be caused by impaired immunity rather than autoimmune reaction, agents that stimulate immune functions may actually be beneficial for people with the inflammatory bowel disease.

There is strong clinical evidence demonstrating that certain probiotics

  • stimulate the release of potent immune cells such as NK (Natural Killer) cells and T lymphocytes
  • enhance phagocytosis (the process by which immune cells engulf and destroy bacterial cells)
  • increase the population of cells known to produce the immunologlobulin, IgA

Therefore, studies suggest that probiotics can improve immune response and allow the body to better cope with bacterial invasion of the gut and better control the misguided immune response to the damage in the intestinal mucosa.

Inflammation

The positive effects of probiotics on the immune system also involve inflammation. Inflammation is a defensive reaction from the immune system. It is meant to contain damage and start the process of healing. However, it can quickly get out of hand and contribute to the attack that triggered it.

Studies show that certain lactobacillus strains can help modulate inflammation and hypersensitivity reactions.

From available results, the effect of probiotics on inflammation is restricted to soft tissues and mucosal surfaces. There are no indications to suggest that skin inflammation improves with probiotics.

However, probiotics can help regulate cytokine functions and the activities of pro-inflammatory immune cells. Research indicate that they can reduce inflammation in inflammatory bowel disease and also reduce hypersensitivity reactions for those with food allergies.

Production of Vitamins

Lastly, patients with Crohn’s disease can benefit from the ability of certain probiotics to synthesize certain essential vitamins.

Studies indicate that some probiotic strains can directly synthesize and release vitamins B12, B9 and K in the gut. These 3 vitamins are not only essential for general health, their deficiencies are actually commonly seen in patients with Crohn’s disease.

Therefore, probiotics may help the body meet its increased demand for folic acid, vitamin K and vitamin B12 during the active phase Crohn’s disease.

Probiotics That May Help Crohn’s Disease
  • Bacillus coagulans and Bifidobacterium longum subsp. infantis – reduce abdominal pain and bloating
  • Saccharomyces boulardii  and Lactobacillus species – relieve acute diarrhea
  • Bifidobacterium animalis subsp. lactis and Lactobacillus plantarum – reduce the gastrointestinal side effects of Crohn’s disease
  • Mixture of Lactobacillus acidophilus and Lactobacillus casei – reduce the symptoms of lactose intolerance and inhibit common bacterial pathogens

Studies on Probiotics and Crohn’s Disease

Negative Studies

While the jury is still out on the benefits and need for probiotics in the management of Crohn’s disease, there are some pretty negative results. One of such studies detailed the ineffectiveness of the probiotic Lactobacillus GG for keeping patients in remission after having sections of their gut removed.

Published in the journal, Gut, in 2002 the researchers gave 37 such patients this probiotic or placebo for one year. The results showed no difference in recurrence rates between the probiotic group and the placebo group.

A 2007 study published in the journal, Inflammatory Bowel Diseases, also covered the same investigation. However, for this study, the probiotic was Lactobacillus johnsonii, LA1.

This multi-center trial recruited patients who have had parts of the ileum and/or cecum removed.

The probiotic and placebo were given to the patients over a period of 12 weeks. Like the Gut study, there was no statistically significant difference in the relapse rate between the two groups.

Besides these 2 studies, three 2008 reviews of past trials done on the benefits of probiotics in the management of Crohn’s disease were more revealing.

A 2008 meta-analysis published in the journal, Digestive Diseases and Sciences, took 8 randomized, placebo-controlled clinical trials from PUBMED and Cochrane databases to determine the effectiveness of probiotics in the management of Crohn’s disease.

This review concluded that probiotics did not maintain patients in remission nor prevent the recurrence of Crohn’s disease.

However, the researchers suggested that the combination of lactobacillus and E. coli or Saccharomyces may provide some benefits.

A 2008 Cochrane review also found that probiotics were not effective for maintaining induced remission in Crohn’s disease.

However, another 2008 Cochrane review reached a slightly different conclusion. Here, the reviewers stated that the studies investigating the benefits (or otherwise) of probiotics in Crohn’s disease were poorly designed.

Therefore, they concluded that there was insufficient evidence to reach a conclusion about the efficacy of probiotics for induction of remission in Crohn’s disease.

Positive Studies

In a 2002 preliminary study published in the journal, Digestive and Liver Disease, a group of researchers investigated the efficacy of Lactobacillus GG for improving the symptoms of 4 teenagers with Crohn’s disease.

The results of the study showed that in 3 of the patients, Lactobacillus GG improved symptoms enough for the researchers to taper down the doses of steroids being given to them.

Even though probiotics were given over a period of 6 months, the researchers reported clinical improvements in the patients in the first week of the study. After 4 weeks, the pediatric Crohn’s disease activity index was reduced by 73%.

A 2002 study published in the journal, Gut, investigated the anti-inflammatory effect of probiotics in Crohn’s disease.

For the study, the researchers obtained ileum tissue specimens from 10 patients with Crohn’s disease as well as 5 control patients. They then took cultured samples from the ileums and incubated them for 24 hours with the probiotics, Lactobacillus casei, Lactobacillus bulgaricus, Lactobacillus crispatus and non-pathogenic Escherichia coli.

The results showed that L. casei and L. bulgaricus reduced the release of proinflammatory cytokines such as TNF-alpha as well as the number of CD4 immune cells.

Lastly, the results showed that the probiotic bacteria did not affect non-inflamed ileum mucosa.

This study demonstrated that probiotic bacteria can indeed reduce inflammation in Crohn’s disease.

In addition, the study showed that probiotics are perfectly safe for normal tissue mucosa. This second conclusion is important because some critics fear that patients with Crohn’s disease may react to beneficial bacteria as if they are pathogenic bacteria.

Conclusion

While the number of negative studies and reviews may make it difficult to fully determine the efficacy of probiotics in Crohn’s disease, mixed results are only to be expected because Crohn’s disease and the effects of probiotics in the gut are not fully understood yet.

One overview published in the journal, Gut, in 2006 tried to explain the mixed results. The author gave these 4 reasons to explain the results of probiotics trials in the management of Crohn’s disease.

  • The part of the gastrointestinal tract affected by Crohn’s disease may determine the outcome of probiotics therapy. For example, when the disease affects the colon, patients tend to respond better to antibiotics. This may suggest that the inflammation in colon is closely tied to the bacteria flora there. Therefore, probiotics may produce better result in Crohn’s disease patients with diseased colons than in patients with diseased ileums.
  • Crohn’s disease is a chronic disease with different and distinct phases. Therefore, probiotics may work better in certain phases. In fact, studies suggests that probiotics produce excellent results in the early phases of Crohn’s disease.
  • Probiotic is a rather broad term to describe a number of beneficial bacteria each with multiple strains. Therefore, a particular strain of a specific bacterium may be the best probiotic for a given phase of Crohn’s disease when it affects certain locations in the gastrointestinal tract. A lot of well-designed studies are required to map out such details.
  • The population and type of invading bacteria may affect the effectiveness of a probiotic. In fact, there are cases when adding another probiotic or giving higher doses was the difference between a successful treatment and a failed one.

The study described below perfectly demonstrates the last point raised by the author.

In this study, a group of Japanese researchers tried to obtain better results in the treatment of Crohn’s disease with beneficial bacteria by combining high dose probiotics with prebiotics.

Prebiotics are non-digestible, fermented food ingredients that can promote the growth of beneficial bacteria (especially Lactobacillus and bifidobacteria species) in the gut. Inulin is a popular example of prebiotics.

Raw foods with high prebiotic content include chicory root, dandelion greens, garlic, Jerusalem artichoke and leek.

For this study published in the Journal of Gastroenterology and Hepatology in 2007, 10 patients with active Crohn’s disease were placed on a combination of probiotics and prebiotics (psyllium) for over one year.

The results showed that 6 out of the 10 patients responded to this combination, 1 patient partially responded while the other 3 did not. Out of the 6 responders, 2 improved enough to discontinue their steroid therapy while 4 were able to reduce their intake.

Sources


http://www.webmd.com/ibd-crohns-disease/ulcerative-colitis/features/ulcerative-colitis-and-probiotics

http://www.crohns.net/Miva/education/whatprobiotics.shtml

http://www.webmd.boots.com/digestive-disorders/crohns-disease-probiotics

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