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Probiotics and IBD inflammation

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					             Probiotics and Inflammatory Bowel Disease

Introduction
There are two main diagnoses of Inflammatory Bowel Disease (IBD); Ulcerative Colitis
and Crohn‟s Disease. The symptoms of both diseases include; diarrhoea, pain, tiredness,
weight loss and constipation. Patients may also experience inflammation in other parts
of the body and suffer from disorders such as arthritis. Ulcerative colitis is characterised
by inflammation in the colon and/or the rectum. Whereas Crohn‟s disease, can occur
anywhere in the gastrointestinal tract, it is commonly found in the terminal ileum or
colon. It is this inflammation, which causes loss of function of the gut including;
reduced ability to absorb nutrients and water, as well as the control of bowel
movements. The disease is characterised by progression through stages of initiation,
amplification and healing.

There are three main factors thought to be responsible for intestinal inflammation
associated with IBD; genetics, the immune system and gut microflora. A gene
associated with Crohn‟s Disease has already been identified and scientists are looking to
find other markers. Researchers studying the immune responses in this disease have
observed abnormal actives of the T-helper cells. Th1 cells, which produce pro-
inflammatory proteins, are overactive, whilst Th2 cells, which produce anti-inflammatory
proteins to not respond in the usual manner.

The role of Bacteria in IBD
Bacterial involvement in IBD has been proven in animal models of inflammatory bowel
disease, where mice kept in a germ free environment did not develop the condition.(6)
However, it is not practical to remove the entire gut microflora, as they have many
beneficial effects on the human hosts, as well as the fact that the gut will quickly
become re-colonised. In human studies, an imbalance in colonic bacteria has been
described in patients with IBD. A reduction in potentially protective organisms such as
Bifidobacteria spp. and Lactobacilli spp., was observed along with an increase in
pathogenic organisms such as Escherichia coli. It is these kinds of pathogens along with
inflammation of the intestinal mucosa, which results in the development of lesions on
the gut wall.(10)

The theory proposed to explain bacterial involvement in IBD is as follows; “a pathogen,
possibly a bacterium, reaches the intestine in large numbers and triggers the immune
system, but instead of stopping when the pathogen has been defeated, the
inflammation carries on as though there were dangerous invaders still present.” (5) It is
thought that this inflammation continues due to the immune system mistakenly reacting
to the normal gut microflora. The cause of IBD may therefore be a malfunction in the
mechanism by which the intestinal mucosa is able to avoid pro-inflammatory responses
to commensal bacteria but able to respond appropriately to luminal pathogens.(7)

                       Protexin Health Care – Technical Notes
                       Probiotics and Inflammatory Bowel Disease
                June 2005 - This document supersedes all previous document
       Probiotics International Ltd., Matts Lane, Stoke sub Hamdon, Somerset, TA14 6QE
                                        www.protexin.com
                                                 1
This process however, does not occur in all individuals; it must be accompanied by one
or more other environmental or genetic factors. The initial trigger for the inflammation
will be when a pathogen passes through the gut mucosa of the intestinal wall. In
normal subjects the epithelial cells form tight junctions and only allow small nutrient
particles of digested food through but patients with IBD have increased gut permeability
(„leaky gut‟), which may also allow bacteria to pass through the gut wall. Several
bacteria have been implicated as possible candidates for the onset and/or persistence of
IBD, including Bacteroides vulgatus for colitis and a specific strain of Escherichia coli for
Crohn‟s disease, which has the ability to cross the intestinal barrier and cause
inflammation.

Treatment of IBD
Unfortunately there is no cure for patients with this condition.                However,
pharmaceuticals, including anti-inflammatories and immuno-suppresants, have been
used to treat some of the symptoms of IBD. These drugs have largely prevented deaths
from this disease but unfortunately patients taking these drugs often experience side
effects, which are sometimes serious. Antibiotics are also often used to control
overgrowth of pathogenic bacteria in specific parts of the gastrointestinal tract.(9)
However, these too can have side effects and broad spectrum antibiotics may also kill
off beneficial bacteria, further exasperating the problem of dysbiosis (gut imbalance/0.
In severe cases of IBD, surgery may even be required to remove part of the intestine.
Food intolerances are often associated with IBD and many patients may experience a
reduction in the severity of symptoms if certain foods are avoided. Special diets are also
used to improve the nutrition of patients and prevent weight loss.

How Probiotics can help
It is thought that if the introduction of beneficial bacteria, in the form of probiotics, can
change the types of bacteria in the gut, then they may be able to alter the immune
response of the gut to it‟s microflora. In other words if you increase the number of
beneficial bacteria and reduce the number of pathogenic bacteria then the immune
system may react in the correct way and not cause continual inflammation. There are
several suggestions as to how probiotic bacteria may do this:

      Adhesion to the wall of the intestine, therefore preventing pathogenic species
       becoming established
      Competition for nutrients, resulting in harmful bacteria being starved and unable
       to increase in number
      Production of lactic acid, reducing the pH within the gut, which is not favourable
       for many undesirable bacteria
      Secretion of bacteriocidal chemicals, which can kill unwanted bacteria
      Influence the immune system to stop incorrect inflammatory responses

Lactobacillus spp. are the most common group of probiotic bacteria and have been
studied for their benefits in treating IBD. Bifidobacteria are also an important part of
                       Protexin Health Care – Technical Notes
                        Probiotics and Inflammatory Bowel Disease
                June 2005 - This document supersedes all previous document
       Probiotics International Ltd., Matts Lane, Stoke sub Hamdon, Somerset, TA14 6QE
                                        www.protexin.com
                                                 2
the normal gut flora and are also often used in probiotic preparations. A single bacterial
strain in unlikely to work for all people with IBD, so a mixed/multi strain probiotic may
be the best choice. Treatment with probiotics has been shown to reduce intestinal
inflammation and inflammatory response in experimental models of colitis and to reduce
symptoms and inflammatory scores in patients with IBD. A study in Ireland used
Lactobacillus salivarius and Bifidobacterium longum in experiments with both mice and
humans, concluding that that they had a beneficial effect of inflammatory bowel
disease.(12) These species were particularly effective in preventing the weight loss
associated with this illness and showed a good ability to colonise the gut and influence
the microflora.

It has been shown that treatment with Lactobacillus plantarum stabilises the gut
mucosal barrier in patients with ulcerative colitis(2) This was measured by a reduction in
gut permeability and a reduction in the concentration of circulating antibody to
endotoxin.(3) It is possible that the mechanism by which probiotics reduce intestinal
inflammation in cases of IBD, is by enhancing the gut barrier. Therefore, colonic
permeability can be influenced by the quality of the flora colonising the mucosal
surfaces.

A type of gut bacterium called Bacteroides are thought to be able to cause IBD,
particularly the pathogenic strain Bacteroides vulgatus, which has been shown to cause
colitis in mice.(11) This may be due to these species ability to drive intestinal
inflammation, whereas Lactobacillus spp. and Bifidobacterium spp. have an ability to
regulate pro-inflammatory and anti-inflammatory responses. Bifidobacterium infantis
strongly inhibited the growth of Bacteroides vulgatus in the coculture and also
significantly suppressed the systemic antibody response raised by B. vulgatus colonising
the gut in germ free mice.(4) These results suggest that Bifidobacterium infantis
protected the gut epithelial layer including the Peyer‟s patches from being invaded by
Bacteroides, thereby suppressing the systemic antibody response raised by Bacteroides.

People with Crohn‟s may suffer from lactose intolerance as the inflammation of the small
intestine reduces it‟s ability to produce enzymes including lactase. Probiotics can help as
many lactic acid bacteria produce lactase themselves and can therefore improve the
ability to digest milk products. Lactobacillus acidophilus and Lactobacillus bulgaricus,
were added to milk and given to people who were lactose intolerant, a significant
improvement in digestion of lactase was observed.(15)




                       Protexin Health Care – Technical Notes
                       Probiotics and Inflammatory Bowel Disease
                June 2005 - This document supersedes all previous document
       Probiotics International Ltd., Matts Lane, Stoke sub Hamdon, Somerset, TA14 6QE
                                        www.protexin.com
                                                 3
The Value of Prebiotics
Prebiotics are defined as „non-digestible food ingredients that beneficially affect the host
by selectively stimulating the growth and or activity of one or a limited number of
bacteria in the colon, that can improve host health‟.(1) In other words prebiotics are food
for the beneficial bacteria within the gut, in this way they complement probiotic bacteria
and strengthen their effect.

Bacteria feed on undigested food that has passed into the intestines, by fermentation
which produces smaller molecules, energy and gases. Prebiotic compounds are usually
indigestible carbohydrates, a soluble form of dietary fibre, which reach the lower part of
the gut.      Most commercially available prebiotics are oligosaccharides such as
fructooligosaccharide (FOS) or longer chain molecules including inulin and
arabinogalactan. Shorter chain sugars are broken down in the upper portion of the gut,
whilst long chain prebiotics like inulin are fermented in the colon.

Lactobacilli spp. and Bifidobacteria spp. specifically ferment carbohydrates, whereas
many pathogenic bacteria ferment protein. In this way prebiotics encourage the growth
of beneficial bacteria, increasing the number of beneficial bacteria particularly
Bifidobacteria. This in turn will help the competitive exclusion process and reduce the
number of harmful bacteria.       Prebiotics also benefit the gut microflora by helping to
prevent pathogenic bacteria colonising the gut wall. Most harmful bacteria can bind to
these carbohydrates but not utilise them as a food source, therefore these bacteria are
drawn away from the gut wall preventing them binding to the epithelial cells.

How prebiotics help IBD
Patients with IBD often have a lower concentration of beneficial bacterial species within
their gut microflora. The addition of these beneficial bacteria in the form of probiotics
on their own or in combination with prebiotics (synbiotics) has been shown to increase
the numbers of Lactobacilli spp. and Bifidobacteria spp, within the gut.(8) Both diarrhoea
and constipation are symptoms of IBD. Probiotics and prebiotics have been seen to
improve the rate of gut transit and stool frequency. Prebiotics have also been shown to
help to prolong remission times in patients with ulcerative colitis. In stimulating the
action of Bifidobacteria, prebiotics can increase the amount of butyrate produced, which
in turn can have an anti-inflammatory action.(13)

Summary
The evidence suggests that increasing the number of beneficial bacteria in the small
intestine and colon, may improve the health of patients suffering from IBD. The result
can include a reduction in the severity of symptoms, increased length of remission
periods and improved immune function. Patients may also be able to reduce their
prescribed medication and even delay or prevent the need for surgery.



                       Protexin Health Care – Technical Notes
                       Probiotics and Inflammatory Bowel Disease
                June 2005 - This document supersedes all previous document
       Probiotics International Ltd., Matts Lane, Stoke sub Hamdon, Somerset, TA14 6QE
                                        www.protexin.com
                                                 4
References
  1. Gibson, G and Roberfroid, MB (1995). Dietary modulation of the Human Colonic
      Microbota: Introducing the Concept of Prebiotics. Journal of Nutrition 125: 1401-1412
  2. Kennedy RJ (2000). The effect of Lactobacillus plantarum species 299 on intestinal
      inflammation and associated gut mucosal barrier dysfunction. Queen‟s University of
      Belfast.
  3. Kennedy RJ, Hoperm, Weir H, et al (2000). Probiotic therapy stabilises the gut mucosal
      barrier in the IL-10 knockout mouse model of colitis. Br j Surg. 87:669
  4. Shiba T, Aiba Y, Ishikawa H, Ushiyama A, Takagi A, Mine T, Koga Y. (2003). The
      suppressive Effect of Bifidobacteria on Bacteroides vulgatus, a Putative Pathogenic
      Microbe in Inflammatory Bowel Disease. Microbiol. Immunol., 47(6), 371-378.
  5. Cartwright P (2003). Probiotics for Crohn‟s and Colitis. Prentice Publishing.
  6. Iizuka H, Takaishi H, Hibi T (2004). Probiotics for inflammatory bowel disease. Nippon
      Rinsho. 63(5):776-80.
  7. Mahida YR, Rolfe VE (2004). Host-bacterial interactions in inflammatory bowel disease.
      Clin Sci (Lond).107(4):331-41.
  8. Sartor RB (2004). Therapeutic manipulation of the enteric microflora in inflammatory
      bowel diseases: antibiotics, probiotics, and prebiotics. Gastroenterology. 126(6):1620-
      33.
  9. Schultz M, Scholmerich J, Rath HC (2003). Rationale for probiotic and antibiotic
      treatment strategies in inflammatory bowel diseases. Dig Dis. 21(2):105-28.
  10. Guarner F (2003). Microecology as a target for therapeutic intervention in inflammatory
      bowel disease. IDrugs. 6(9):868-73.
  11. Desreumaux P, Colombel JF (2003). Intestinal flora and Crohn's disease. Ann Pharm Fr.
      61(4):276-81.
  12. Dunne C, Murphy L, Flynn S, O'Mahony L, O'Halloran S, Feeney M, Morrissey D, Thornton
      G, Fitzgerald G, Daly C, Kiely B, Quigley EM, O'Sullivan GC, Shanahan F, Collins JK
      (1999). Probiotics: from myth to reality. Demonstration of functionality in animal models
      of disease and in human clinical trials. Antonie Van Leeuwenhoek. 76(1-4):279-92.
  13. Kanauchi O, Matsumoto Y, Matsumura M, Fukuoka M, Bamba T (2005). The beneficial
      effects of microflora, especially obligate anaerobes, and their products on the colonic
      environment in inflammatory bowel disease. Curr Pharm Des. 11(8):1047-53.
  14. Lin MY, Yen CL, Chen SH (1998). Management of lactose maldigestion by consuming milk
      containing lactobacilli. Dig Dis Sci. 43(1):133-7.
  15. Lin MY, Yen CL, Chen SH. Management of lactose maldigestion by consuming milk
      containing lactobacilli (1998). Dig Dis Sci. 43(1):133-7.




                      Protexin Health Care – Technical Notes
                       Probiotics and Inflammatory Bowel Disease
              June 2005 - This document supersedes all previous document
     Probiotics International Ltd., Matts Lane, Stoke sub Hamdon, Somerset, TA14 6QE
                                      www.protexin.com
                                               5

				
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