fight back against inflammatory bowel disease

7/28/2019 Fight Back Against Inflammatory Bowel Disease

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Fight back against inflammatory bowel disease

Michael W. Day RN, CCRN, MSN Nursing2008November 2008Volume 38 Number 11

Pages 34 - 40

Abstract

It takes guts to live with Crohn's disease or ulcerative colitis, both of which can take a heavy toll on their

victims. Find out how to help your patient tame the attacks.

WHEN A PATIENT is admitted to your unit with a diagnosis of inflammatory bowel disease (IBD), she

has one of two disorders: Crohn's disease or ulcerative colitis. Both cause chronic diarrhea, abdominal pain,

fever, arthritis of the spine and large joints of the arms and legs, and anorexia, and both can be extremelydebilitating, even life-threatening. But they're not the same disease, and you must understand the difference

to intervene appropriately. In this article, I'll discuss the similarities and differences, including diagnostic

tests and treatments for each and what nursing care and teaching you must be prepared to provide for yourpatient after the diagnosis.

Similar but not the same

Crohn's disease and ulcerative colitis are classified as IBD because they're characterized by chronic

inflammation at various sites in the gastrointestinal (GI) tract. The inflammation usually causes diarrheaand abdominal pain. Both types of IBD are chronic, wax and wane in severity, and can cause signs and

symptoms in other parts of the body. However, ulcerative colitis, which is confined to the colon, can be

cured by removing the colon. Because Crohn's disease can affect the entire GI tract, it's considered

manageable but incurable.

Both types of IBD can strike at any age but most patients first experience problems between ages 10 and30, with a smaller peak incidence between ages 50 and 60. The risk is higher among white patients

compared with nonwhites and among Jewish patients compared with those with a non-Jewish background.

Both diseases have a familial tendency: 10% to 20% of patients with IBD have at least one relative who

also has IBD.1Research indicates that both diseases stem from dysfunction of the epithelial cells in the GItract and that a distinct immunologic process is responsible.2

Although no single feature absolutely distinguishes Crohn's disease from ulcerative colitis, the disorders

generally differ in several ways. For example, ulcerative colitis is usually confined to the rectum and lower

colon, with inflammation limited to the intestinal wall's inner lining. In contrast, Crohn's disease typically

affects the lower part of the small bowel (ileum) but may extend throughout the GI tract. In addition,inflammation can affect all layers of the intestinal wall.1(SeeHow Crohn's disease and ulcerative colitiscompare for more distinguishing features.) In the few patients in whom the disease can't be differentiated,

the diagnosis is indeterminate colitis.

Figure. No caption available.

Precise causes of IBD aren't well understood, although an induced immune reaction in people with a

genetic predisposition is probably involved.2Possible triggers for the immune reaction include diet,environment, and infection. For unknown reasons, smoking increases the risk of Crohn's disease but
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decreases the risk of ulcerative colitis.1,3For more about IBD risk factors, see What increases the risk ofIBD?

Beyond the GI tract

The underlying inflammation of IBD can lead to disorders elsewhere in the body. For example:

* erythema nodosum causes tender, erythematous nodules, most often on the ankles or shins

* pyoderma gangrenosum, a painful and progressive destructive skin disorder, is characterized by deep skin

ulceration

* peripheral arthritis in large joints may or may not involve joint swelling and redness

* stomatitis.

These disorders tend to flare and resolve along with IBD attacks. Other syndromes that may be related toIBD but don't coincide with exacerbations include uveitis, ankylosing spondylitis, and primary sclerosing

cholangitis (PSC), a chronic liver disease involving inflammation and scarring of the bile ducts. In fact,

PSC may precede the diagnosis of IBD by years and always merits an investigation for IBD. Patients withIBD also have a greater incidence of thromboembolic events and may develop abnormal liver function

tests, indicating liver disease.4

Nutritional deficiencies are a particular problem in IBD, especially in Crohn's disease. Loss of appetite,

malabsorption of nutrients, increased calorie requirements, loss of electrolytes and protein, and the effects

of therapy contribute to nutritional deficiencies.

Now let's take a closer look at each disorder, starting with Crohn's disease.

Crohn's disease: "Skip" the lesions

Although Crohn's disease can involve the entire GI tract, only rarely does it affect the esophagus, stomach,

or duodenum. However, mouth ulcers are common. The most common complication is intestinal

obstruction.3

Crohn's disease is characterized by well-demarcated lesions, called "skip" lesions, surrounded by tissue that

appears normal. The lesions penetrate the bowel's submucosal layer but don't usually extend to bowel

muscle.

Table. How Crohn's disease and ulcerative colitis compare

As Crohn's disease progresses, the affected portion of the bowel becomes semirigid and thickened. Chronicinflammation causes hypertrophy of bowel muscle, leading to fibrosis and strictures. All these changes can

lead to abscesses, fistulas, and bowel obstruction.

About 30% of patients with Crohn's disease develop fistulas, usually in high-pressure areas just proximal to

strictures. These may penetrate nearby structures, including the bladder, other bowel loops, or muscle, and

become infected. An enterocutaneous fistula may extend out of the abdominal cavity, causing bowelcontents to leak through a skin opening. Most fistulas occur in the perianal area.5

Signs and symptoms of Crohn's disease vary, depending on how long the patient has had the disease. Initial
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symptoms may be mistaken for appendicitis or bowel obstruction. The patient may initially report fever,persistent diarrhea, and cramping abdominal pain. When disease is confined to the small bowel, the patient

will pass larger volume stools without urgency or tenesmus (ineffectual straining to pass stool). Rectal

bleeding, although less common, can occur if he has lesions in the colon.

Pain related to abscesses, obstruction, or adhesions from previous surgeries is common as the disease

progresses; draining fistulas are less common. Other common signs and symptoms include fever, weightloss, and various non-GI syndromes.

Malnutrition results from the disease itself, which destroys healthy bowel tissue, and the surgery that some

patients require. Removing a significant portion of the small bowel leads to malabsorption, typically

causing deficiencies in electrolytes, minerals, fat-soluble vitamins, and vitamin B12. These deficiencies can

lead to clotting disorders, bone demineralization, and delayed growth and development in children. Thedegree of malabsorption is usually related to the extent of small-bowel involvement.

Pinning down the diagnosis

Crohn's disease mimics many other disorders, and no single test is diagnostic. The healthcare provider will

rely on the patient's history and results of various tests to rule out other disorders, such as diverticulitis or

appendicitis, and make the diagnosis.

*Lab studies include a complete blood cell count, which may reveal anemia and leukocytosis; liver

function tests; and a basic metabolic panel. Inflammatory markers, such as erythrocyte sedimentation rate

and C-reactive protein, and nutritional markers, such as albumin, prealbumin, and transferrin, help the

healthcare provider monitor disease progress.

*Imaging studies commonly include plain abdominal X-rays and computed tomography or magnetic

resonance imaging of the abdomen. In women, ultrasound of the abdomen and pelvis may be indicated torule out gynecologic problems.

*Endoscopy allows the clinician to visualize lesions in the colon up to the terminal ileum and removespecimens for biopsy.

* Capsule endoscopy, a newer procedure, may provide better images of the small intestine. The patient

swallows a capsule containing a tiny camera, which radios data to a sensor as it passes through the GI

tract.6

*Barium contrast studies, such as an upper GI series, can help define the distribution and severity of

disease. A barium enema may be indicated when diarrhea is the primary symptom, indicating greater colon

involvement.

Managing Crohn's disease with medication

Although Crohn's disease isn't curable, various interventions can help the patient cope with debilitating

signs and symptoms. For example, cautious use of the antidiarrheal loperamide, taken just before meals,can help him manage cramping and diarrhea. Bulking laxatives (psyllium [Metamucil]) increase stoolfirmness and may help prevent anal irritation from diarrhea.4

However, these drugs mustn't be used when Crohn's disease affects the colon because they could trigger

toxic megacolon, a potentially life-threatening condition (see Toxic megacolon takes a tollfor details).
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For more about drugs commonly prescribed to manage Crohn's disease, seeManaging IBD medically.

Surgical options

Up to 75% of patients with Crohn's disease undergo some type of surgery, usually to remove lesions.

However, surgery is never the first choice because it doesn't cure the disease. About 50% of patientsexperience a recurrence of symptoms within 5 years, and about half of these need more surgery. But long-

term drug therapy following surgery may help maintain remission.7

If the patient develops a bowel obstruction, he'll be treated initially with gastric suctioning, I.V. fluids, and

possibly parenteral nutrition (PN). Obstructions associated with Crohn's disease generally resolve within

days, but if they don't, surgery is usually indicated.

If the patient develops significant fever and vomiting, rebound tenderness, or a palpable abdominal mass,

he also needs hospital admission for treatment with I.V. fluids and antibiotics and drainage of abscesses, if

present. Once infection is ruled out or controlled, he may begin corticosteroid therapy. If he doesn't respondwithin a week, surgery is usually indicated.

A patient who develops perianal fistulas may need a temporary diverting colostomy, but fistulas almost

always recur when the colostomy is reversed. For this reason, a diverting colostomy is used as a temporarymeasure until definitive surgery can be done to resect the colon.

Ulcerative colitis: Confined to the colon

Although a few patients recover completely after one episode, ulcerative colitis is usually chronic and

characterized by remissions and exacerbations. The course and severity vary widely, from relatively benign

to severely debilitating. The risk of colon cancer increases with the length of time a patient has ulcerativecolitis and the amount of bowel involved.

Unlike Crohn's disease, ulcerative colitis is confined to the large bowel, with lesions usually developing

initially in the rectum. And unlike the skip lesions of Crohn's disease, the lesions of ulcerative colitis arecontinuous. Typically they affect only the mucosa (inner lining of the intestinal wall), but they may extend

into the submucosal muscle layer in severe disease.2

In the early stages of ulcerative colitis, mucosa is edematous and friable with areas of bleeding. As the

disease progresses, the lesions produce large amounts of purulent drainage. If lesions extend into themuscle layer, the bowel loses tone and begins to dilate, raising the risk of toxic megacolon.

Classic signs of ulcerative colitis

Intermittent bouts of bloody diarrhea between periods of normal bowel movements is a classic sign of

ulcerative colitis. Tenesmus is common. The frequency of signs and symptoms varies with disease severity.

* With mild disease, the patient may have normal stools yet leak blood, mucus, and pus with or between

bowel movements. He may also have mild cramping, urgency, and diarrhea.

* A patient withsevere disease may have 30 to 40 bowel movements a day, primarily watery stool withsignificant amounts of blood, mucus, and pus. Diarrhea attacks are commonly accompanied by fever,

abdominal pain, and cramping. Some patients lose so much blood that they become anemic. Nighttime

diarrhea may interrupt sleep and further debilitate the patient. Diarrhea also causes significant electrolyte


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imbalances, particularly hypokalemia.

*Fulminant colitis, in which ulcerative colitis lesions penetrate the bowel muscle, is characterized by

sudden, violent diarrhea with rebound tenderness, abdominal pain, and toxemia. Some patients have thesesigns and symptoms during the initial episode of the disease. Fulminant colitis may also cause toxic

megacolon or bowel perforation.

Along with acute signs and symptoms, ulcerative colitis may cause weight loss, malaise, fever, anemia, and

anorexia. Other parts of the body are also affected by flares (disease exacerbations), so the patient maydevelop arthritis or a skin condition such as erythema nodosum.

Testing for ulcerative colitis

For a definitive diagnosis of ulcerative colitis, many other conditions must be ruled out. Diagnostic testing

is similar to that for Crohn's disease.

*Lab studies. A complete blood cell count and albumin and basic metabolic panel are useful to evaluate the

patient's overall health. Anemia may point to intestinal bleeding. Stool samples for culture and sensitivityand tests for ova and parasites and Clostridium difficile toxin help rule out other causes of diarrhea.

*Endoscopy and biopsy. Because ulcerative colitis usually develops first in the rectum, the healthcareprovider may start with a sigmoidoscopic examination. If lesions extend beyond the left colon, he may

perform a colonoscopy. Collecting tissue samples for biopsy may help identify the cause of lesions.

*Imaging studies. Endoscopy and biopsies typically eliminate the need for plain abdominal X-rays,

although X-rays may help the healthcare provider identify large accumulations of gas or toxic megacolon.

He may also order a barium enema study to outline lesions.

A word of warning: Endoscopy and barium enemas are contraindicated in patients with toxic megacolon

because these procedures could cause perforation.

Treatment options for ulcerative colitis

As with Crohn's disease, medical management of ulcerative colitis aims to establish and maintain disease

remission. SeeManaging IBD medically for details on drug therapy to manage flares and maintainremission.

From 25% to 35% of patients with ulcerative colitis may require some type of surgery.8The reasonsinclude cancerous lesions, strictures, complications such as toxic megacolon, or recurrent and severe signs

and symptoms that cause significant hardship for the patient. Unlike surgery for Crohn's disease,

proctocolectomy (removal of the rectum and colon) cures ulcerative colitis.

Here's a quick look at two widely used surgical options.9

Proctocolectomy with ileostomy. After removing the colon, rectum, and anus, the surgeon creates a stoma

in the abdominal wall. Intestinal waste drains from the end of the ileum through the stoma into an ostomy

pouch.

Restorative proctocolectomy. If the patient isn't critically ill and his anal sphincter is free from lesions, thesurgeon may remove the colon and rectum but leave the anus intact. He then forms an internal pouch fromthe distal ileum and connects it to the anal sphincter, allowing the patient to have continent bowel


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movements. (This option usually requires two surgical procedures.) After healing in about 12 months, thetypical patient will have five or six bowel movements a day but remain continent.

Up to 30% of patients who have this procedure develop pouchitis (inflammation of the ileal pouch), whichis treated with an antibiotic such as ciprofloxacin or an antiprotozoal such as metronidazole. If

inflammation persists, the ileal pouch may be converted to another type of ileal diversion, such as a Kock

pouch or ileostomy. Small-bowel obstruction, a less common complication, usually responds to bowel restand conservative treatment, but some patients require surgery to remove the blockage.8

If necessary to treat massive hemorrhage or perforation, the surgeon may perform a subtotal colectomy with

an ileostomy and a mucous fistula. (The remaining colon is attached to the anus.) This is a relatively quick

intervention to treat an acute, life-threatening complication. Later, the surgeon will perform definitive

surgery, removing the rectal stump to prevent recurrence of ulcerative colitis or cancer.4

When your patient has an ileostomy, he continues to lose fluid and electrolytes. Without the colon, his body

can't reabsorb GI fluids, and the ileostomy effluence is very watery with a high concentration ofelectrolytes. Over time, however, the GI tract becomes more efficient at absorbing water and electrolytes.

Nursing considerations for IBD

When you care for a patient with Crohn's disease or ulcerative colitis, use the following measures to helpmanage his signs and symptoms, monitor for complications, and promote healing and well-being.

Manage the eff ects of diarr hea. For most patients, diarrhea is the worst symptom of IBD. Perform thesemeasures and teach your patient how to do them at home: Thoroughly clean the rectal area after each bowel

movement to decrease pain and skin irritation, using nonirritating cleansers and wipes. Apply a barrier

cream after cleaning to help protect sensitive skin. If the perianal skin is damaged, apply a rectal pouch to

protect it from contact with stool.

L imi t activity. Encourage the patient to take intermittent rest breaks during the day to conserve energy.

During acute attacks, curtailing activity will decrease gut motility.

Monitor stool. Monitor the amount, consistency, and color and assess it for blood. Tell the patient to reportchanges to his healthcare provider.

Moni tor f lu id and electrolyte levels. Diarrhea can cause large losses of fluids and electrolytes, so routinelymonitor the patient's fluid status and evaluate lab results.

Manage your patient' s pain. Assess pain using a valid and reliable pain intensity rating scale. Changes inthe nature or intensity of pain may indicate a worsening condition, so report them immediately; your

patient's treatment plan may need to change dramatically. Administer pain medications as scheduled,

assessing the nature and intensity of pain beforehand and afterward. Opioid medications are usually usedsparingly because they increase the risk of toxic megacolon.

Provide postoperative care. If your patient's colon has been removed but the rectal stump remains, he'llhave an ileostomy and a mucous fistula. If the rectum and anus are also removed, he'll have an ileostomyalone. In both cases, frequently monitor the stoma, which should be red and moist but not painful. A dusky

appearance, cyanosis, or pallor indicates compromised blood supply. Monitor the stoma output for color,

consistency, and amount. Assess the patient for abdominal pain or distension, indicating possible ileus.Finally, when his nasogastric tube is removed, slowly advance his diet as ordered.


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Provide nutr iti onal support. The patient needs nutritional support to help reverse wasting from IBD. If hehas mild disease, he may get adequate nutrition from a low-fat diet supplemented with vitamins and

minerals while he undergoes medical treatment.

A patient who's undergone surgery or who has severe disease may require PN. While on PN, he may also

receive enteral feedings at 5 to 10 mL/hour to continue nutrition to his small bowel. As he's slowly weaned

from PN, gradually increase his enteral feedings. Consult with a dietitian as indicated.

Help the patient adapt. Because of body image changes, chronic diarrhea, and other persistent problems,most patients with IBD have significant psychosocial issues. Many patients say that fecal incontinence (or

fear of it) is the most limiting aspect of the disease.

Altered body image is a significant issue with anyone who has an ostomy. As soon as possible, show the

patient his stoma and the associated equipment so he can begin to integrate it into his body image. Use

proper terms to describe anatomy and the stoma equipment and encourage him to help with stoma care.

Provide care in an open, accepting manner and encourage the patient and his family to express their feelingsabout the stoma.

Provide your patient and his family with resources so they realize they aren't alone in dealing with IBD.

They can find resources at the Crohn's and Colitis Foundation (http://www.ccfa.org in the United States andhttp://www.ccfc.ca in Canada).

Living with IBD

By understanding IBD and the measures needed to manage its various manifestations, you're better

prepared to help him through disease exacerbations and live more comfortably with his disease.

Toxic megacolon takes a toll

When the colon dilates to a diameter greater than 6 cm in a short time (usually 1 to 2 days), the patient has

toxic megacolon, a life-threatening complication of IBD. Use of antidiarrheal drugs to significantlydecrease GI motility sometimes precipitates this complication. Signs and symptoms include abdominal

pain, tenderness, and distension; dehydration; fever; and tachycardia. Potentially fatal consequences oftoxic megacolon include perforation, sepsis, shock, and systemic inflammatory response syndrome.

Treatment for toxic megacolon associated with IBD includes I.V. corticosteroids, placement of a longintestinal tube, fluid and electrolyte replacement, and antibiotics. The healthcare provider may consider

placing a soft rectal tube to decompress the colon, but he must use extreme caution to avoid perforating

friable tissue. If the patient doesn't respond to conservative treatment in 24 to 48 hours, he'll need a

colectomy to save his life.

What increases the risk of IBD?

Inflammatory bowel disease is considered primarily an immune system disorder with a strong genetic

component. Having a relative with IBD increases the risk by about 10 times; the risk is 30 times greater ifthe relative is a brother or sister.6Psychological factors, although probably not a direct cause, cancontribute to the onset and severity of IBD. These factors may also influence disease development:

* Smokingincreases the risk of Crohn's disease but decreases the risk of ulcerative colitis.1,3
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*Breast-feedingdecreases the child's future risk of both Crohn's disease and ulcerative colitis.10

Managing IBD medically

The goal of treatment for IBD is to establish and maintain remission. A low-fiber diet may help the patient

prevent or manage diarrhea. If his IBD affects the colon, warn him not to use antidiarrheal medicationsbecause of the risk of triggering toxic megacolon.

Drugs in the following categories are mainstays of treatment for IBD.

* Aminosalycilates, which contain the compound 5-aminosalicyclic acid (5-ASA), reduce inflammation in

the GI tract. Examples include sulfasalazine and mesalamine, which are available in oral formulations;mesalamine is also available in enema and suppository form for treating inflammation in the rectum and

lower colon. Numerous but infrequent adverse reactions, including nausea, fatigue, and headache, limit the

usefulness of this treatment for some patients. But if the patient responds to therapy and tolerates it well, he

may continue on maintenance therapy to prolong remission.

* Antibioticsmay be prescribed initially, depending on signs and symptoms, or later if the patient fails torespond to several weeks of treatment with 5-ASA. If he has recurrent fistulas or abscesses, he may

continue to take an antibiotic such as ciprofloxacin as long-term therapy.

* Corticosteroidssuch as prednisone and methylprednisolone are another option if the patient doesn't

respond to 5-ASA or has significant pain, fever, or vomiting. These drugs, which help reduce inflammation,

are usually given orally but are also available as enemas and suppositories. Generally they're used tomanage disease flares, not as maintenance therapy. But budesonide (Entocort EC), a newer corticosteroid

approved to treat mild to moderate Crohn's disease, may be continued for up to 3 months to maintain

remission.

* Immunomodulatorssuch as azathioprine, 6-mercaptopurine, or methotrexate help reduce immune system

activity. Associated with fewer adverse reactions than corticosteroids, they may be used to maintain

remission.

* Biologic r esponse modif ierssuch as infliximab (Remicade), adalimumab (Humira), and certolizumab(Cimzia) block tumor necrosis factor, a component of the inflammatory response. Given by I.V. infusion,

these drugs help control inflammation, trigger remission, and allow fistulas to close. Although generally

well tolerated, they may cause infusion reactions, malignancies, and potentially serious infections (see 'TNF

blockers: Stronger labeling warns of fungal infections' inDrug News on page 14 of this issue). Because ofthese risks, they're generally reserved for patients who haven't responded well to other therapies.

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8. About ulcerative colitis and proctitis. Crohn's and Colitis Foundation of America, 2008.

http://www.ccfa.org/info/about/ucp .[Context Link]

9. Surgery for ulcerative colitis. Crohn's and Colitis Foundation of America, 2008.http://www.ccfa.org/info/surgery/surgeryuc .[Context Link]

10. Klement E, et al. Breastfeeding and risk of inflammatory bowel disease: A systematic review with

meta-analysis.Am J Clin Nutr. 2004; 80(5):1342-1352.[Context Link]

Bamias G, et al. New concepts in the pathophysiology of inflammatory bowel disease.Ann Intern Med.2005;143(12):895-904.

Cima RR, Pemberton JH. Medical and surgical management of chronic ulcerative colitis.Arc Surg-Chicago. 2005;140(3):300-310.

Collins P, Rhodes J. Ulcerative colitis: Diagnosis and management.Brit Med J. 2006;333(7563):340-343.

Colombel JF, et al. Adalimumab for maintenance of clinical response and remission in patients with

Crohn's disease: The CHARM trial. Gastroenterology. 2007;132(1):52-65.

Lichtenstein GR, et al. American Gastroenterological Association Institute technical review ofcorticosteroids, immunomodulators, and infliximab in inflammatory bowel disease. Gastroenterology.

2006;130(3):940-987.

Copyright 1996-2004 Lippincott Williams & Wilkins, Inc., A Wolters Kluwer Company. All rights

reserved.
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Probiotics and Prebiotics as Functional Ingredients in Inflammatory Bowel Disease

Mirjam A.C. Looijer-van Langen MD

Vimal PrajapatiLevinus A. Dieleman MD, PhD

Nutrition TodayNovember/December 2008Volume 43 Number 6

Pages 235 - 242

Abstract

Probiotics and prebiotics are promising nutraceuticals that may exert a beneficial effect in many medical

conditions including inflammatory bowel disease. With the increasing occurrence of antibiotic resistance,the search for medication with little side effects, and the need for options for patients with inflammatory

bowel disease who are unresponsive to current therapies, research into alternative therapeutic options is

justified. Preclinical studies have provided insights into the effects of probiotics and prebiotics on theimmune system and gut microbiota. This new information, along with the older evidence, shows that

probiotics and prebiotics may ameliorate chronic intestinal inflammation. This article gives a short

overview on current knowledge of probiotics and prebiotics.

Inflammatory bowel diseases (IBDs) are chronic inflammatory disorders that include Crohn disease (CD),

ulcerative colitis (UC), and chronic pouchitis. Crohn disease can affect the entire gastrointestinal tract

anywhere from mouth to anus. The chronic inflammation is not limited to the lining of the bowel but affects

the entire bowel wall, sometimes resulting in intra-abdominal abscesses and fistula (abnormal connectionsbetween the lumen of the bowel, other organs, or the surface of the skin) and intestinal obstruction. Patients

typically experience symptoms of mild diarrhea, right lower quadrant pain, and low-grade fever. Ulcerative

colitis is limited to the colon, and patients experience rectal bleeding, abdominal pain, and diarrhea. The

inflammation in UC is confined to the upper layer of the colonic wall and the mucosa. Patients with CD andthose with UC both experience periods of remission and relapses. Chronic pouchitis is a chronic

inflammation of the ileoanal pouch. An ileoanal pouch is an internal reservoir, constructed for patients with

UC who have had their large intestine surgically removed mostly because of severe inflammation refractoryto medical treatment. Patients with pouchitis typically present with bloody diarrhea, urgency in passing

stools, or discomfort while passing stools. Rarely, pain occurs with pouchitis.

Inflammatory bowel disease is caused by multiple factors that disturb intestinal homeostasis. An abnormal

immune response to commensal bacteria or dietary factors in genetically susceptible hosts plays a major

role in the pathogenesis. Environmental factors including psychological stress, use of nonsteroidal anti-inflammatory drugs, and cigarette smoking can also contribute to IBD. The current treatment of IBD

mainly consists of drugs directed against the overactive adaptive immune response, such as 5-

aminosalicylic acid compounds, steroids, azathioprine/6-mercaptopurine, methotrexate, cyclosporine, and

biologics such as infliximab. Most patients respond well to these medications, but for some, it is inadequate

or induces intolerable adverse effects. Therefore, interest has been raised in nutraceutical therapies such asprobiotics, prebiotics, or a combination of these, calledsynbiotics, as a good therapeutic option for

nonresponding patients with IBD.

The concept that ingestion of certain bacteria may promote health is not new. Fermented milk

products have been consumed by human beings for thousands of years with the belief that they

provide health benefits.1For example, according to Persian tradition, Abraham of the Old Testament

owed his longevity to sour milk.2

In the early 20th century, the Russian immunologist, Elie Metchnikoff, proposed that ingestion of


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lactic acid bacteria promoted health and longevity of life.3He based his theory on the observation

that Bulgarians who consumed large quantities of fermented milk lived longer than those who did

not. Around the same time, the first attempt to treat disease with bacteria was made by Dr Henry

Tissier, a French pediatrician, who discovered Y-shaped or "bifid" bacteria (now known as

Bifidobacterium) and recommended administration of isolated bifid cultures to infants with diarrhea

to help restore a healthy gut flora.4Metchnikoff and Tissier are largely credited for being the first

individuals to make scientific suggestions about probiotic bacteria, although the term probioticwas

not coined until 1965.

The term probiotic, which literally means "for life," was first introduced by Lilly and Stillwell5in

1965 to describe "substances produced by one microorganism which stimulate the growth of

another." Since that time, the definition has undergone many revisions. In an attempt to provide an

agreed upon definition, a joint Food and Agricultural Organization/World Health Organization

Expert Consultation redefined probiotics as "live microorganisms which when administered in

adequate amounts confer a health benefit on the host."4Currently, this is the most widely accepted

definition.

Probiotics can be bacteria or yeast, although the vast majority is bacteria. The most common

bacteria used as probiotics are lactic acid bacteria from the genera Lactobacillusand

Bifidobacterium. Certain species from other genera such as Streptococcus, Enterococcus, andEscherichiahave also been used but to a lesser extent. The only yeast that is considered a probiotic is

Saccharomyces boulardii(Table 1). Probiotics are available in a variety of food products, especially

dairy products such as yogurt, milk, cottage cheese, and dietary supplement products. Dietary

supplements containing freeze-dried probiotics in capsule, powder, or tablet form are becoming a

popular choice.

Table 1. Common Probiotic Organisms

Multiple mechanisms of action have been postulated to account for the beneficial effects of probiotics

in IBD. In broad terms, probiotics are thought to improve the epithelial barrier function of the

intestine, alter the composition of the intestinal microflora, and modulate the immune response of the

intestinal mucosa. However, the exact mechanism is likely to vary from one probiotic organism to

another (Table 2).

Table 2. Proposed Benefits of Probiotics to the Well-being and Health of the Animal

Host

Normal epithelial barrier function of the intestine requires an intact layer of epithelial cells and an

adequate production of overlying mucus to prevent uptake of potentially harmful organisms and

substances into the body. A disrupted and leaky intestinal epithelial barrier may be one of the

initiating events in the pathogenesis of IBD.6In addition, increased apoptosis (programmed celldeath) of intestinal epithelial cells and decreased mucus production have been documented in

patients with IBD and are thought to contribute to the pathogenesis. Several probiotics have

demonstrated the ability to enhance the epithelial barrier function of the intestine. For example,

Lactobacil lus rhamnosusGG improves barrier function by inhibiting apoptosis of intestinal epithelial

cells.7Streptococcus sali variussubsp thermophilusand Lactobacil lus acidophilushave been shown to

enhance the tight junctions between epithelial cells, thereby preventing infection from the invasion of

pathogenic bacteria such as enteroinvasive Escherichia coli.8Also, several Lactobacillusstrains have

been found to increase mucus production.9Madsen10showed that a synthetic probiotic mixture,

VSL#3 (containing 4 Lactobacillusspp, 3 Bifidobacteriumspp, and S salivariussubsp thermophilus),

also restored the epithelial barrier function in a chronic colitis mouse model. The improvement of the
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barrier function is probably the result of a direct effect of probiotic bacteria or their secreted

bacterial products.

Normally, there is a balance between the beneficial bacterial species and the detrimental bacterial

species that make up the intestinal microflora. In IBD, a number of genetic and environmental

factors are thought to upset this balance such that there is a relative predominance of detrimental

disease-inducing bacteria that contribute to the chronic inflammatory process in IBD.11Probiotics

can help restore a healthy intestinal microflora by directly increasing the population of beneficial

bacteria and by suppressing the growth and function of detrimental bacteria. For example,Bif idobacterium inf antishas been shown to suppress the growth ofBacteroides vulgatus, a pathogenic

microbe possibly responsible for the induction and perpetuation of IBD.12

Probiotic organisms can inhibit pathogenic bacteria in several ways. First of all, they competitively

exclude pathogens by occupying the limited physical space available for colonization in the gut. In

addition, probiotic organisms can either directly secrete antimicrobial substances (eg, organic acids,

hydrogen peroxide, and bacteriocins) and/or stimulate host intestinal cells to secrete antimicrobial

substances (ie, defensin molecules), which destroy pathogens before they can colonize the gut.13

Several probiotics have demonstrated the ability to prevent epithelial adhesion and invasion of

pathogenic bacteria. For example, E coliNissle 1917 inhibits epithelial adhesion and invasion of a

pathogenic E colistrain isolated from patients with CD.14

Inflammatory bowel disease is thought to be caused by an overly aggressive immune response to the

endogenous gut microflora in genetically susceptible individuals. This results in an increased

production of chemical signals that promote inflammation. These proinflammatory cytokines

include, for example, tumor necrosis factor [alpha] and interferon [gamma]. Anti-inflammatory

cytokines are interleukin 10 and transforming growth factor [beta]. Probiotic organisms are

generally thought to modify the immune system of the intestinal mucosa by reducing the production

of proinflammatory cytokines and increasing the production of anti-inflammatory mediators. Studies

have shown that Lactobacil lus plantarum, L rhamnosusGG, and VSL#3 can increase the production

of interleukin 10 and that specific lactobacilli and bifidobacteria species can reduce the production of

tumor necrosis factor [alpha] and interferon [gamma].15,16The mechanisms by which probioticsexert their immunomodulatory effects are complex and beyond the scope of this review.

Probiotics are generally well tolerated and have an excellent overall safety record. This is not

surprising because many of the organisms used as probiotics are commensal, nonpathogenic

inhabitants of the human gut and have been used safely in the production of fermented foods for

centuries. The most common adverse effects of probiotics include bloating, flatulence, and

constipation. There have been some reports of probiotics inducing serious infections such as bacterial

and fungal sepsis. However, these cases occurred in immunocompromised patients. There are no

reports of such cases in healthy people.1

Animal models have been used extensively to study the efficacy of probiotics in treating chronicintestinal inflammation and to elucidate the mechanisms by which probiotics work. Successful

reduction of intestinal inflammation in many of these experimental models has provided the support

for human clinical trials16,17(Table 3). Escherichia coliNissle 1917, VSL#3, and bifidobacteria-

fermented milk have been shown to have some success at inducing and maintaining remission of UC

and reducing disease activity.22,25

Table 3. Clinical Studies Testing Probiotics in the Treatment of Human Inflammatory

Bowel Disease
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VSL#3 proved to be effective in maintaining remission of chronic relapsing pouchitis, preventing the

development of pouchitis compared with placebo treatment; in addition, it also significantly

improved patient quality of life.20One study with L r hamnosusGG, however, was ineffective in

reducing pouchitis disease activity.30

The efficacy of probiotics in CD is still controversial. For example, Lactobacil lus salivarius, VSL#3,

and S boulardiiin combination with conventional therapy (mesalamine) have had some success.29On

the other hand, there are numerous studies reporting the ineffectiveness of various probiotics inCD.31-35

Because the viability of probiotics in some food products and during transit through the

gastrointestinal tract is variable, the prebiotic concept has been developed. Prebiotics are

nondigestible short-chain carbohydrates, originally defined as selectively fermented ingredients that

allow specific changes, both in the composition and/or activity in the gastrointestinal microflora that

confer benefits upon host's well-being and health.36

Substances are considered prebiotics according to the following conditions:

(1) when they are not broken down nor absorbed by enzymes in the upper part of the mammaliangastrointestinal tract,

(2) when they are selectively fermented by one or a limited number of potentially beneficial bacteria

in the intestine, and

(3) when they are able to alter the colonic microflora toward a healthier composition .36,37

Prebiotics have become very popular food ingredients. The most commonly used prebiotics, inulin

and oligofructose, are natural food ingredients or dietary fibers present in plants as storage

carbohydrates. Wheat, chicory, bananas, onions, leeks, Jerusalem artichokes, asparagus, and garlic

contain prebiotics. Most commercially used prebiotics are synthesized from sucrose or extractedfrom chicory roots. They are used in, for example, confectioneries, bakery products, fruit juices,

desserts, spreads, taste improver, sweetener, and fat replacers and sometimes used as viscosity-

increasing agents.38

Inulin and oligofructose, also called [beta]-fructans, are composed of fructose units joined by [beta]-

glycosidic links. Because of their different fructose chain lengths, inulin and oligofructose are used

for different purposes. Inulin has a longer chain length and is therefore less soluble and suitable as a

fat replacer.

Oligofructose is composed of a shorter chain length of fructose molecules and is, for example, used to

replace sugar.39Depending on the diet, the daily intake of prebiotics in Western societies varies from3 to 13 g per day.40

Many substances are claimed to have prebiotics effects but only fructo-oligosaccharides, galacto-

oligosaccharides, lactulose, and inulin have been shown to meet all 3 before mentioned criteria.41

Other potential prebiotic candidates42are mentioned inTable 4.

Table 4. Potential Candidate Prebiotic Substrates

Different medical conditions have been speculated to ameliorate upon treatment with prebiotics,
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including improvement of mineral absorption, reduced risk for colon cancer, improvement of food

allergies, alleviation of constipation, regulation of lipid metabolism, and reduction of antibiotic-

induced diarrhea.38,43

The working mechanisms of prebiotics are not fully understood yet, but many theories have been

formed (Table 5).44,45In broad terms, the beneficial effects are believed to be due to the stimulation

of protective intestinal organisms and the production of short-chain fatty acids (SCFAs) as

fermentation products of prebiotics.

Table 5. Proposed Benefits of Prebiotics to the Well-being and Health of the Animal Host

The intestinal barrier functions to protect the individual from potential bacterial threats. The mucus

layer in the gastrointestinal tract plays a major role by preventing the attachment and translocation

of bacteria across the epithelial wall. A decrease in mucus production is seen in IBD. Prebiotics have

been shown to increase the mucus layer in a rat model of colitis.46

As mentioned before, intestinal bacteria play an important role in the pathogenesis and attenuation

of IBD. Prebiotics change the intestinal microflora in animal models and human studies by increasing

the numbers of intestinal protective bacteria, for example, lactobacilli and bifidobacteria, and

decreasing the proportion of pathogenic bacteria.47Several studies performed in infants confirmed

this, showing that the intestinal microbiota of breast-fed infants (containing milk oligosaccharides) is

generally dominated by bifidobacteria and lactic acid bacteria. In contrast, formula-fed infants'

intestinal microflora contains lower numbers of bifidobacteria and lactic acid bacteria and contains

more bacteroides, clostridia, and enterobacteriaceae.48However, after the prebiotic diet is stopped,

these microflora changes gradually return to baseline levels.49

Short-chain fatty acids include butyrate, acetate, and propionate. Butyrate is the major energy

source for colonic epithelial cells and plays an essential role in the maturation of colonic epithelium,

regeneration of mucosa, induction of epithelial cell differentiation, and stimulation of their

apoptosis.40A reduced level of luminal SCFAs may play a role in the onset of IBD. The amount of

SCFAs produced in the colon depends on the composition of intestinal microflora, their substrates,

and the gut transit time. Fermentation of prebiotics by colon bacteria results in higher luminal SCFA

production, which results in acidification of the colonic content. Intraluminal acidification may

inhibit the growth of harmful or disease-inducing bacteria.50

Several studies show that the prebiotic effects are different for each prebiotic substance and that

these depend on intestinal pH, prebiotic dosages, intraluminal concentrations of prebiotics, duration

of intake, locations in the gut where fermentation occurs, and composition of endogenous intestinal

microflora.40

Prebiotics have been part of human diets for centuries and are generally recognized as safe to

consume. However, they can cause symptoms of abdominal pain, eructation, flatulence, bloating,

abdominal cramps, and diarrhea.38There are some reports of increased bacterial translocation of

pathogenic bacteria during prebiotic treatment, such as Salmonella, and in sepsis models, but these

results are controversial and are not seen in patients.51More research in this area is needed.

The effects of prebiotics are most extensively studied in different rodent models of IBD. Various

efficacy of prebiotics and synbiotics (combination of probiotics and prebiotics) in different IBD

models was found, but in most studies, prebiotics seem to ameliorate intestinal inflammation.

Inulin,52starch,53lactulose,54combination of oligofructose and inulin,55and goat milk

oligosaccharides56reduced colitis. Some fructo-oligosaccharides showed mixed results, whereas
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galacto-oligosaccharides57failed to reduce intestinal inflammation.

Currently, only a few studies with prebiotics in patients with IBD have been published. Emerging

small short-term studies using prebiotics or synbiotics showed reduction of inflammation in patients

with pouchitis, UC, and CD (Table 6). A small open-label study in patients with active ileocolonic CD

treated with a combination of oligofructose and inulin showed a significant reduction in disease

activity.60A recent pilot study investigated the adjunct effect of oligofructose-enriched inulin in

patients with mild to moderate UC with concomitant 5-aminosalicylic acid treatment (n = 19). This

placebo-controlled study reported a significant reduction of fecal calprotectin (marker of intestinalinflammation) in the prebiotic-treated patients compared with the placebo group, suggesting that

these prebiotics reduced chronic intestinal inflammation.62

Table 6. Clinical Studies Testing Prebiotics or Synbiotics in the Treatment of HumanInflammatory Bowel Disease

A randomized double-blind crossover study in pouchitis patients after colectomy for UC treated with

inulin resulted in the reduction of mucosal inflammation58However, Chermesh et al61could not

show prevention of relapse of CD after surgical resection with synbiotic treatment, although this

study may be underpowered.

Conclusion and Future Perspectives

Probiotics and prebiotics are emerging as promising therapeutic options for the treatment and

prevention of flare-ups of IBD. A significant number of studies in both animal models and human

IBD have documented the efficacy of these therapies in ameliorating chronic intestinal inflammation.

In addition, these studies have led to a greater understanding of the mechanisms by which probiotics

and prebiotics exert their beneficial effects. However, it is important to remember that the

mechanisms elucidated cannot be generalized, as not all probiotics and prebiotic have similar

therapeutic effects. Probiotics and prebiotics are widely available, are easy to consume, and are

recognized as safe to consume. Side effects are rare, but some adverse effects such as bloating and

flatulence tend to limit subsequent intake. The results obtained thus far warrant further rigorous

well-designed and larger clinical trials to firmly establish the safety and efficacy of probiotics and

prebiotics in IBD.

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