From The December 2000 Issue of Nutrition Science News
by Dan Lukaczer, N.D.
Bacterial balance can be the most significant factor influencing gut ecology and health
Colitis, or irritable bowel disease (IBD), is a group of conditions characterized by gut-wall inflammation. Conventional medicine generally addresses IBD symptoms with steroids and other drugs. Probiotics, or "friendly" bacteria, address the root cause, most importantly by acting antagonistically toward pathogenic bacteria that cause intestinal inflammation. Valuable probiotics include various species of Lactobacillus and Bifidobacterium. In addition, certain foods have been shown to initiate or aggravate IBD symptoms.
Many people with serious medical conditions seek solutions at health food stores and from complementary health care practitioners. The reasons why people look beyond the HMO and Western medicine are varied, but certain conditions tend to send sufferers searching more than others. One such condition is colitis, or inflammatory bowel disease (IBD). A recent review of patients with IBD by researchers at the University of Calgary found that more than half of them were using complementary therapies, with vitamins and herbal products the most commonly reported. 
The reason individuals with IBD look for an alternative is simple: In conventional medicine, the most common symptom-control strategy involves steroids, immunosuppressive drugs and salicylic acid derivatives such as sulfasalazine and mesalamine. However, accompanying these drugs are adverse effects including anemia, easy bruising, frequent infections and mood swings. Thus, many people prefer the disease symptoms to side effects. Also, complementary medicine is seen as a way to be more involved with one's own health and treatment as well as a modality that goes to the root of the problem rather than just treating symptoms.
IBD is a general term for a group of diseases involving gut-wall inflammation. Chronic IBD is generally divided into two major groups: Crohn's disease and ulcerative colitis. Although some significant differences exist in their location and the way they affect the bowel wall, they both cause abdominal pain and cramping with frequent, urgent, loose bowel movements marked by blood, mucus and pus. Fatigue is more common in Crohn's patients, while ulcerative colitis patients may have tenderness along the colon. Complications of both can include abscesses and infections, fistulas, hemorrhoids, intestinal wall perforations, malabsorption of nutrients and weight loss. IBD in general can increase the risk for gastrointestinal cancer. Additionally, the disease can have systemic effects including arthritic symptoms and fatigue. IBD can be a chronic, relapsing and debilitating condition. It can affect one's lifestyle and mental state and cause social embarrassment and isolation. Many patients with IBD face the possibility of long-term drug use with significant side effects, multiple hospitalizations and surgery to remove diseased sections of the intestine.
IBD should be differentiated from the less-serious irritable bowel syndrome (IBS). IBD involves actual physical changes associated with intestinal wall inflammation that can be noted on diagnostic laboratory tests. IBS can be a painful and perplexing condition, but there is no known anatomical cause, and it is therefore considered a diagnosis of exclusion that is, if everything else can be ruled out, IBS may be diagnosed.
The best way to diagnose IBD accurately is with a barium swallow for Crohn's disease or barium enema for ulcerative colitis. These tests allow the clinician to observe the characteristic inflammatory changes of the bowel wall. Although it is not as prevalent as IBS, IBD in the United States affects about 250,000 individuals, or approximately one case for every 1,000 people. 
Considerable debate has centered on IBD's underlying etiology. Because 20 percent of IBD patients have a relative with the disease, some researchers suggest genetic predisposition plays a significant role in its onset. In children who develop IBD, the likelihood of another immediate family member having the diagnosis is greater than 40 percent.  However, the etiology of IBD is obviously more complicated than simple genetic inheritance. Environmental factors undoubtedly contribute. One theory proposes that changes in the bacteria residing in the gut lumen may lead to an improperly regulated immune response. When the intestine's immune defenses are chronically stimulated, a cascade of chronic inflammation results. Another theory suggests an intake of dietary allergens contributes to IBD development. These allergens disrupt immune system function, again resulting in inflammation. In both scenarios, a defective mucosal barrier leads to uptake of bacteria or allergens and results in a chronic inflammatory response. Therefore, understanding the possible causative role of these bacteria and allergens begins with an evaluation of how the intestinal lining may be compromised.
Impaired Mucosal Integrity
The integrity of the gut barrier is influenced by three categories of factors: genes, nutrition and toxic load. Challenges in any of these areas can lead to poor nutrient absorption, increased intestinal permeability or both. Genetics plays a role in gut health not only through the genes present at birth, but also in how those genes are expressed during life's circumstances. Genetic impairments in the physical, chemical or immunological processes in the gut can result in compromised mucosal integrity to the point where pathogens penetrate into systemic circulation. Nutrition and toxic burden undoubtedly influence how the genes are expressed. Poor nutrient intake or absorption cannot support the regeneration of healthy epithelia and therefore can profoundly affect gut integrity. Impaired nutrition can further decrease absorption and accelerate loss of mucosal integrity. Lastly, internal and external toxins such as bacterial by-products and food additives also affect the gut. [3, 4]
Fortunately, the gastrointestinal system has physical and chemical defenses to prevent systemic antigenic exposure. First, for an antigen to pass across the intestine's epithelial lining, it must overcome a complex array of interdependent and complementary host defense mechanisms ranging from tight cellular junctions, a thick mucosal coat, intestinal peristalsis, acidic secretions and proteolytic enzymes as well as immunologically mediated defenses. The combination of these physical and chemical barriers helps defend the body against an excessive antigenic load.
Second, proper digestive function is key. This digestion starts in the mouth and continues through the stomach, which is appropriately acidified; then food moves into the duodenum where digestive enzymes and bile further reduce the antigenic load. Individuals who are hypochlorhydric or achlorhydric, have pancreatic insufficiency, or have bile acid insufficiency may consequently deliver more unprocessed antigens into systemic circulation.
The third barrier of antigenic exclusion is the gut-associated immunological defense. The intestine is generally recognized as the largest lymphoid organ in the body, encompassing the greatest number of lymphocytes and generating almost 70 percent of the antibodies.  When potentially deleterious substances penetrate the gastrointestinal barrier, the result is an immune reaction from the gut-associated lymphoid tissue. This reaction helps limit antigenic penetration through the gastrointestinal barrier without compromising the function or integrity of the intestinal tract.
Research suggests that malfunction or impairment in these processes can lead to a variety of diseases, among them inflammatory bowel disease.  The link between IBD and compromised intestinal integrity is clear. Small intestinal and colonic epithelial cells are the first host cells to interact with ingested food antigens or bacterial organisms. This interaction can result in immune activation and secretion of proinflammatory molecules. These molecules, as well as molecular messengers classified as cytokines, initiate mucosal damage resulting in the death of epithilial cells, poor regereration and increased permeability. This further activates exposed immune cells clustered in the tissue surrounding the exterior intestinal wall, and a vicious inflammatory cycle ensues.  The two areas of focus in IBD, then, are bacterial balance and food allergens.
Probiotics and Bacterial Balance
With more than 400 microorganism species residing in the human gastrointestinal tract, their overall balance can profoundly influence gut ecology and health. Intestinal bacteria produce toxins and antitoxins, alter chemical composition of foods and drugs, produce and degrade vitamins, degrade dietary toxins and inhibit the growth of certain pathogens. Gut-derived products may also play a role in increasing the systemic immune inflammatory response.  Bacterial lipopolysaccharides found in the cell walls of gram-negative bacteria, for example, have been shown to initiate immune responses and elevate pro-inflammatory cytokines. 
A fundamental question is whether people with IBD have pathogenic flora, an unbalanced amount of flora, or simply an overly aggressive, improperly regulated immune response toward some of the normal bacteria. Recent studies in animals with experimentally induced IBD indicate that the amounts of normal resident bacteria are a significant factor in the onset and chronic nature of IBD. In humans with Crohn's disease, the bacterial balance can be quite different than that of a normal gut, with some resident bacteria increased and some decreased.  Other animal studies support the idea that resident bacteria and not necessarily pathogenic foreign germs are to blame for the development of chronic intestinal inflammation.  Additionally, and just as importantly, all intestinal bacterial species do not exhibit equal abilities to induce colitis.  So although the trigger may be unknown, the protective qualities of "friendly" probiotic bacteria may provide an important approach to treatment.
How might probiotics work in this situation? Perhaps the most important function of probiotics is their antagonistic activity toward pathogens and other resident bacteria, which probiotics perform in a variety of complementary ways.
The first activity has been called colonization resistance the ability of normal flora to protect against the unwanted establishment of pathogen populations.
Second, probiotics may produce various antimicrobial substances. For instance, Lactobacillus casei GG (LGG) has been shown to produce substances inhibitory toward a broad spectrum of gram-positive and gram-negative pathogens.  Other probiotics have demonstrated antimicrobial activity as well. 
Competition for nutrients is a third activity. By competing for available nutrient substrate, beneficial bacteria can inhibit the growth of other, less favorable flora.
Competition for bacterial adhesion sites is probiotics' fourth strategic activity. For instance, Lactobacillus acidophilus inhibits the adhesion of several enteric pathogens to human intestinal cells.  A related activity is enzymatically modifying a toxin receptor. Studies using Saccharomyces boulardii, a beneficial yeast, indicate that its interactions with host cell receptors may be important in reducing the pathological effects of infections. 
A fifth activity involves a systemic effect. Human LGG, administered orally, has been shown to increase various markers of immune response. 
These varied activities may also decrease the likelihood that pathogens will develop resistance against probiotic agents. Thus, probiotics may be viewed as a vehicle to neutralize or inhibit other bacteria in the gut, and increase or stimulate host immune stimulant activities as well. 
Human studies suggest beneficial bacteria have a positive effect in IBD patients. A small trial at Tampere University Hospital in Finland measured the effect of LGG in patients with Crohn's disease. Despite the short duration of treatment (10 days) and the small number of subjects (14 children), the authors found LGG promoted a positive immune response and concluded it may have the potential to promote and fortify the gut immunological barrier. 
More recently, a double-blind comparison trial at the University of Cologne, Germany, tested a specific, beneficial, oral E. coli preparation and the drug mesalamine for maintaining remission in patients with ulcerative colitis. This 12-week study included 120 patients and compared the effect of 500 mg mesalamine three times/day or an oral preparation of a viable E. coli strain. Relapse rates were not statistically different in either group, and the authors concluded that probiotics offered another option for maintenance therapy in patients with ulcerative colitis in remission.  In another study, at the University of Bologna, Italy, 15 patients with ulcerative colitis were treated with a combination of probiotics. After one year, 80 percent of the patients (12 of 15) were in remission. 
From these human trials, it is clear that gut bacteria play a major role in initiating and perpetuating chronic inflammatory bowel disease. While research is not conclusive, there appears to be enough preliminary evidence to suggest probiotics produce beneficial effects in IBD patients.
Beneficial bacteria are present in foods including yogurt and kefir, but supplements are also helpful and more concentrated. Frequently supplemented species include Bifidobacterium bifidus, B. longum, B. breve, Lactobacillus acidophilus, L. bulgaricus, L. thermophilus, L. sporogenes, L. casei GG and Saccharomyces boulardii.
Supplementing with what are referred to as prebiotics is also important. Prebiotics are generally defined as food sources that friendly bacteria preferentially choose. Prebiotics are really a subset of fiber. Some important prebiotics include fructooligosaccharides and inulin, derived from foods such as asparagus, chicory, garlic, Jerusalem artichoke and onion. All support this indirect bolstering process. [21,22]
Another interesting fiber source is arabinogalactan, a naturally occuring fiber found in carrots, tomatoes and other vegetables, and in particularly high concentrations in the larch tree (Larix occidentalis). Certain strains of beneficial bacteria appear to preferentially feed off of arabinogalactans. 
Food Allergy and Intolerance
During the course of a lifetime, the gastrointestinal tract processes more than 25 tons of food, which represents the largest antigenic load confronting the human immune system.  During digestion, proteins and large peptides are broken down into amino acids or small peptides within the intestinal lumen, which also removes or decreases their antigenic potential.  In a healthy intestinal tract, more than 98 percent of ingested food proteins are blocked from entering circulation by the gastrointestinal barrier functions previously described. This means a healthy gut absorbs only a small proportion of whole food proteins intact.  In a compromised gastrointestinal environment, with impaired digestion or increased intestinal permeability, significantly more antigens can penetrate into the systemic circulation and cause reactions. Individuals may also be genetically predisposed to food reactions. In any case, food allergies or intolerant reactions may occur.
Can identifying a food allergy or intolerance be useful for treating IBD? Are there specific foods or food groups that can be linked to the initiation or aggravation of IBD? In both cases, the answer seems to be a qualified yes. A review article on the use of elemental diets, which limit many possibly allergenic foods, showed remission rates of 85 percent with Crohn's disease patients.  Effects are noted generally within two to four weeks.  Elemental diets seem to be particularly effective in children. 
Several studies identify foods that cause reactions in some IBD patients. The culprits include beans, citrus fruits, eggs, fish, milk, peanuts, wheat and salicylate-rich foods such as certain berries and other fruits.  Unfortunately, the prevalence of these sensitivities among IBD patients varies. For instance, dairy may account for only 20 percent of the food allergic reactions in patients with IBD. 
Managing IBD symptoms is challenging, but sustaining remission is also quite difficult. A 199193 multicenter British study compared the results of steroids to an elimination diet on remission qualities. After the two-year study on 136 patients, researchers observed a significant difference in improvement and length of remission with diet vs. steroid therapy.  However, other studies do not reach the same conclusions.  It does appear possible, through trial and error, to establish diets on which individual patients achieve long-term remission. However, there is no universal diet that will help all patients with IBD. 
IBD is a serious, chronic, perplexing health disorder. As with so many chronic diseases, it is the combination of genetics and environment the persistent stimulus in an individual who has a genetic predisposition to this disease that determines the outcome. For alternative or adjuvant strategies in managing IBD, health care practitioners and patients should work with the nutritional tools of probiotics and elimination diets.
Factors Involved in the Increased Intestinal Permeability Found With Irritable Bowel Disease
Probiotics Counter Antibiotics
Dan Lukaczer, N.D., is director of clinical research at the Functional Medicine Research Center, a division of Metagenics Inc. in Gig Harbor, Wash.
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