# Food elimination based on IgG antibodies in irritable bowel syndrome:



## eric (Jul 8, 1999)

FYIGut 2004;53:1459-1464ï¿½ 2004 by BMJ Publishing Group Ltd & British Society of Gastroenterology--------------------------------------------------------------------------------IRRITABLE BOWEL SYNDROME Food elimination based on IgG antibodies in irritable bowel syndrome: a randomised controlled trial W Atkinson1, T A Sheldon2, N Shaath1 and P J Whorwell1 1 Department of Medicine, University Hospital of South Manchester, Manchester, UK2 Department of Health Sciences, University of York, York, UK Correspondence to: Dr P J Whorwell Department of Medicine, University Hospital of South Manchester, Manchester M20 2LR, UK; peter.whorwell###smuht.nwest.nhs.ukABSTRACTBackground: Patients with irritable bowel syndrome (IBS) often feel they have some form of dietary intolerance and frequently try exclusion diets. Tests attempting to predict food sensitivity in IBS have been disappointing but none has utilised IgG antibodies. Aims: To assess the therapeutic potential of dietary elimination based on the presence of IgG antibodies to food. Patients: A total of 150 outpatients with IBS were randomised to receive, for three months, either a diet excluding all foods to which they had raised IgG antibodies (enzyme linked immunosorbant assay test) or a sham diet excluding the same number of foods but not those to which they had antibodies. Methods: Primary outcome measures were change in IBS symptom severity and global rating scores. Non-colonic symptomatology, quality of life, and anxiety/depression were secondary outcomes. Intention to treat analysis was undertaken using a generalised linear model. Results: After 12 weeks, the true diet resulted in a 10% greater reduction in symptom score than the sham diet (mean difference 39 (95% confidence intervals (CI) 5ï¿½72); p = 0.024) with this value increasing to 26% in fully compliant patients (difference 98 (95% CI 52ï¿½144); p 0.001). Global rating also significantly improved in the true diet group as a whole (p = 0.048, NNT = 9) and even more in compliant patients (p = 0.006, NNT = 2.5). All other outcomes showed trends favouring the true diet. Relaxing the diet led to a 24% greater deterioration in symptoms in those on the true diet (difference 52 (95% CI 18ï¿½88); p = 0.003). Conclusion: Food elimination based on IgG antibodies may be effective in reducing IBS symptoms and is worthy of further biomedical research.


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## 13577 (Oct 3, 2006)

I did the IGG food scann 2 years ago and it saved my life. AFter being told by 2 docs that I had IBS. After 1 month on the diet and I was 100% cured.


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## eric (Jul 8, 1999)

From Current Opinion in GastroenterologyDiet and Irritable Bowel SyndromePosted 03/06/2006David H Alpers IntroductionThe prevalence of irritable bowel syndrome (IBS) has increased over the last 50 years in countries where a Western style diet has been prominent or introduced.[1*] Compared with previous centuries, such diets generally contain less fiber and complex starch and more refined sugars and chemical additives. There is a sense that more food allergies, especially to recent additives, may be expressed. In addition, meals tend to be eaten on a more irregular or hurried basis. Despite these changes, relatively few carefully controlled studies on the effect of diet or dietary components (with the exception of lactose) on symptom generation have been carried out in IBS patients. Part of this paucity of information results from confusion between food intolerance, food allergy, the effect of intestinal bacterial flora on ingested food, and food 'sensitivity' that is not related to physiological intolerance or to true allergy. This review will briefly consider recent findings in each of these areas.Does Diet Really Have an Effect on Irritable Bowel Syndrome Symptom Generation?Before exploring the possible reasons for food-generated symptoms in IBS, it would be worth considering the evidence in favor of such an association. Plasma serotonin levels are increased in patients with IBS, and symptoms are more prominent after meals.[2*] For these reasons, some have considered serotonin central to the pathophysiology of IBS. The peak increase in plasma serotonin, however, was not well coordinated with the time when patients most often experience postmeal symptoms (60-90 min after the meal).[3]The dietary component most associated with the pathogenesis of IBS is dietary fiber. One current hypothesis for generation of IBS is that as dietary fiber content has decreased, higher pressures in the descending colon have occurred, leading to the development of diverticula as well as to IBS-like symptoms.[4] As a result, one 'standard' form of therapy in IBS has been the use of supplemental fiber, attempting to restore a daily fiber intake of around 25 g. Although one of the known effects of dietary fiber is to increase the number of bowel movements in healthy adults, fiber intake may not be correlated with transit time.[5] The addition of wheat bran (10-20 g/day) increases stool weight, but does not alter symptoms in patients with IBS.[6*] There have been relatively few well controlled studies of fiber interventions, but a recent review included nine studies of 482 patients using a dichotomous outcome for global assessment of improvement.[7**] No effect of fiber intervention was seen, thus not lending support to the theory of fiber depletion in IBS.IBS is defined in the Rome II criteria as abdominal pain that is associated temporally with some change in bowel pattern or consistency. A factor analysis in two community samples of adult women established that variables that explained more than 16% of the variance and factored together in both samples included loose bowel movements with the onset of pain, pain relieved by bowel movements, and increased bowel movements with pain.[8] These factors have been almost canonical aspects of the Rome II criteria for IBS (Rome II). A gastrointestinal reaction to food was the only other variable that accounted for over 16% of variability in both samples (and lactose malabsorption tests did not correlate with this variable), but reaction to food has not been accepted as a critical component of IBS.More recently, a symptom-specific questionnaire (Irritable Bowel Impact Scale, IBS-IS) was developed for use in clinical trials in an attempt to measure the impact of a wide range of IBS symptoms on the clinical outcome.[9*] The final list of symptoms was developed after discussion with experienced physicians, nurses, and patient focus groups. This list of 26 symptoms included four related to eating habits: 'avoided foods, careful eating, worried food is trigger, food unappealing'. None of these symptoms is related to diet per se, but all are related to eating. The first two topics to be reviewed below (food intolerance and food allergy) are related to specific dietary components, whereas the latter two (effect of intestinal flora on a meal and food sensitivity) are best defined as related to the act or consequences of eating.Food IntoleranceFew randomized controlled trials of food intolerance have been reported.[10] Burden reviewed eight studies of food elimination; five demonstrated intolerance, but three did not. A major problem with these studies is that they included mostly patients who felt that food was a problem. Two studies of food withdrawal confirmed only 15% and 6% of patients with the suspected intolerance,[11,12] whereas one found that most patients had reported intolerance that responded to food withdrawal.[13] None of the patients in these studies, however, were rechallenged with the food of interest.Food components to which people are often intolerant include lactose, wheat products, monosaccharides (sorbitol, fructose, xylitol), and caffeine (in coffee, chocolate, cocoa, tea, cola, sodas).[10,14] The response to many foods is thought to be nonspecific by some experts, leading to the recommendation that diets be individualized in patients with IBS.[15*] The prevalence of food intolerance in the general population is about 15%,[16] but there is a discrepancy between reported intolerance and the result of controlled blinded trials of food withdrawal. About 45% of IBS patients appear to have lactose malabsorption, but only 30% have symptoms with milk products, and only 52% are improved with withdrawal of milk products. Lactose intolerance is difficult to evaluate because of the ability of bacterial metabolism in the colon to convert the malabsorbed sugar to metabolites that can be absorbed in the colon. Despite this difficulty in interpretation, such results have led to the suggestion that some of the symptoms attributed to food intolerance are in fact psychogenic in origin. This assessment is complicated by the observation that overeating leads to more gastrointestinal complaints.[16]Intestinal gas may be increased by certain foods, rising from around 15 ml/h in patients on a low-fiber diet to 170 ml/h when given a high-fiber (bean) diet.[17] The authors concluded that gas absorption may be impaired, but increased production could not be excluded.Food intolerance is commonly encountered in IBS patients as well as in the general population, but may be more noticeable in the IBS patient. Although discovery and treatment of intolerance(s) may improve symptoms, the patient is often left with significant residual symptoms that are due to the underlying IBS. Dietary management of food intolerances thus is an adjunct of IBS treatment.Food AllergyIncreases in antigen-specific IgE antibodies can be found in most children under 5 years of age, but these antibodies do not remain in significant titer in later years.[18] Thus, true allergy to food is much more common in children than in adults, but does occur in adults, often without an increase in total IgE levels. Such an allergy needs to be identified in patients with a suggestive history, and the food withdrawn before a diagnosis of IBS can be made with confidence. Symptoms produced are commonly pain, bloating, and diarrhea, but the orofacial syndrome is the most common manifestation of food allergy, without accompanying bowel symptoms.[19] The oral allergy syndrome is usually seen in patients with allergic rhinitis and conjunctivitis and is triggered by tree, grass, or weed pollens. The oral syndrome following food is triggered by cross-reacting allergens in certain foods. The most common food allergens are proteins found in milk, eggs, fish, nuts, shellfish, soybeans, and wheat.[14] Diagnosis of food allergy has been suggested by skin prick tests, total serum IgE levels, and food-specific IgE levels identified in the radioallergosorbent (RAST) test. Skin atopy patch testing is a more recent method of allergy testing, but its advantage in food allergy over the skin prick test has yet to be established.[20*]A recent study selected diets based on the presence of serum IgG antibodies against foods, and showed that IBS symptoms improved on such diets using a randomized, placebo-controlled study design.[21*] The diets of the two groups, however, were not comparable, in that only the treated group had diets restricted in yeast, milk, egg, and wheat, foods often associated with food intolerance in IBS patients. The specificity of the IgG test is still not documented by this and other studies.[20*] Desensitization trials based on the usual tests for diagnosis of food allergy have not shown a clear answer.[19] Results are rather more clear in peanut allergic patients, as the major peanut antigen produces a strong IgE response, and one that can be modified by infusion of anti-IgE antibodies.[22]Another implicated source of food allergens is yeast, although a low yeast diet is not a recognized and validated diet. The usual yeast exclusion diet forbids a wide range of foods, including baked goods, milk products, commercial cereals and juices, meat products, B vitamin preparations, and foods containing added sugars. Thus, this diet excludes many of the foods to which IBS patients (and others) are intolerant. IBS symptoms are somewhat like those of the 'Candida syndrome'.[23*] This latter syndrome is not well defined, and is associated with other comorbid somatic conditions, so its validity as a separate entity is questionable. Two placebo-controlled trials of antifungal therapy have shown mixed results. The 'Candida syndrome' has been implicated in a variety of disorders, including coronary artery disease, but scientific evidence for its importance is lacking.All that can be said at present about food allergy in IBS is that as yet unidentified antigens in food or the intestinal lumen might prove to be of importance in IBS.Bacterial Flora and Pro/PrebioticsSome patients with IBS, estimated at between 4 and 26%, will develop the disorder after an episode of acute gastroenteritis, although such patients characteristically have only diarrhea without constipation.[24] The reasons for this association are not clearly defined, and the occurrence of other life stresses or other potentially confounding concurrent etiological factors have not been systematically examined. When they are, the postinfectious group are found to have more of them.[24*,25*] The association with intestinal infection, however, raises the possibility that some interaction between the intestinal bacteria and the intestine itself may be altered. There is evidence from germ-free animals that motor and sensory function mediated by the enteric nervous system is altered, and can be corrected by the addition of bacteria.[26*] Moreover, changes in motility occur in patients with small intestinal bacterial overgrowth (SIBO).[26*] A randomized trial of neomycin in IBS patients produced more symptom improvement than in controls, especially in those patients whose lactulose breath test had normalized, consistent with elimination of SIBO.[27] Moreover, the lactulose breath test was abnormal in patients with fibromyalgia, a condition often occurring with IBS.[28*]Many factors are thought to be important in altering bacterial flora in the human intestine, including stress, diet, and antibiotics.[29*] Because flora are indeed altered in IBS, trials of various probiotic organisms have been attempted to alleviate symptoms. Of eight controlled trials, six showed some evidence of benefit, with five using only a single organism.[30*] The total number of patients treated (265 total) is small, however. One study tested two individual organisms in 77 patients, and the bifidobacterium strain, in contrast with the lactobacillus organism, provided benefit on pain and bloating.[31**] The benefit was suggested to be due to alteration in cytokine production, but was only modest. Quality of life measures were minimally affected. Diet type (Western, Japanese, Indian, etc.) can affect human gut microflora, but bifidobacteria are not the most affected by these various diets that reflect differences in IBS prevalence.[29*]The hypothesis that symptoms in IBS may be due to changes in cytokine production from the intestine is intriguing. Cytokines can produce many of the nongastrointestinal symptoms seen in IBS (e.g. fatigue, nausea), and have been implicated in depression, a condition that is present in many IBS patients.[32] More data are needed to determine whether cytokines are implicated in IBS symptomatology and, if so, whether bacterial profile or SIBO are factors in producing those symptoms.Multiple Chemical SensitivityDepression and anxiety and other psychiatric disorders occur in association with IBS, features that have led to the use of cognitive behaviour therapy for IBS.[33] Moreover, other somatic syndromes (e.g. fibromyalgia) occur with IBS. These associations could account for many of the nongastrointestinal features of IBS.[34] Among the many functional syndromes that cluster with IBS is multiple chemical sensitivity (MCS).[35] This syndrome does not have a widely agreed definition, but is an acquired disorder that is thought to occur in relation to some illness or environmental insult, involve more than one organ system, and has no known cause.[36] Symptoms recur with the same stimulus, are due to a variety of chemicals whose effects can be demonstrated, and occur at exposure levels that are tolerated by normal persons. Food is one of the chemical groups that can trigger such a syndrome. A model containing three elements has been suggested that allows for such a symptomatic state, and is consistent with IBS. These elements include a person with a biomedical condition that produces hyperreactivity, exposure to a substance that is detected by the patient but not demonstrable in the tissues at risk, and risk factors for developing or reporting symptoms.[37] Somatization is a condition that is seen in many patients with IBS and that is characterized by heightened reporting of symptoms.[38] Somatization (the reporting of multiple medically unexplained physical symptoms) is suggested when symptoms are numerous and involve more than one organ system, coexist with psychiatric symptoms, follow traumatic events, and represent a predictable personality trait for the patient.In this setting it may be worthwhile considering that some IBS patients may have MCS, and that food might function as a trigger for chemical intolerance. Food intolerances are a recognized component of MCS, and may trigger 'every sort of digestive difficulty, feeling ill after meals' and may produce symptoms of gas, bloating, altered bowel habits, pain, insomnia, depression, headache, joint pain, and fatigue.[39] Nearly all chemically intolerant patients report one or more problems with food or drugs, and over half the patients felt that the diet affected many of their symptoms. Somatic symptoms are very common in the population of patients felt to have MCS,[40] but very little is known or agreed upon concerning this syndrome. Still, it appears to represent one part of the somatization complex that is seen in patients who over-report symptoms.ConclusionThe response to food in IBS patients appears to be multifactorial. This response includes food intolerances, food allergies, and very possibly an alteration in bacterial flora with consequent changes in intestinal function. Modulating these responses might be an underlying psychiatric framework that includes over-reporting, characterized by somatization or MCS. None of these factors likely occurs in all patients with the heterogeneous disorder known as IBS, nor is it likely that any or all of these factors occur in isolation in a given patient. For all these reasons it seems unlikely that dietary manipulation will improve symptoms in a consistent manner in groups of IBS patients. For the moment, until our understanding is better, it is best to discover and treat individual intolerances/allergies/sensitivities, recognizing that alteration in this aspect of the therapeutic program will likely cause only partial improvement, especially in patients who over-report symptoms.Abbreviation NotesIBS = irritable bowel syndrome; MCS = multiple chemical sensitivity; SIBO = small intestinal bacterial overgrowthReprint AddressCorrespondence to David H. Alpers, Washington University School of Medicine, 660 S. Euclid Ave., Campus Box 8031, St Louis, MO 63110-1093, USA Tel: +1 314 362-8943; fax: +1 314 362 8230; e-mail: dalpers###im.wustl.edu Curr Opin Gastroenterol. 2006;22(2):136-139. Â©2006 Lippincott Williams & Wilkinshttp://www.medscape.com/viewarticle/524230_1


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## eric (Jul 8, 1999)

With permission Fall 2005 Nutritional Intervention for IBS Bette Bischoff Fourth Year Medical Student University of Kansas Medical Center IBS Bette Bischoff Background Prior to medical school when I was a practicing dietician, I had the privilege of working with many patients who had irritable bowel syndrome (IBS). I found the subject of nutritional intervention related to IBS to be very rewarding and often challenging because there is no â€œperfectâ€ diet for this syndrome. In light of the different etiologies potentially at work in each patient with IBS, nutrition therapy should be carefully and thoughtfully tailored to each person. This can be likened to times past when a cobbler hand-made each personâ€™s shoes. Since each IBS patient can differ dramatically, careful documentation of exacerbating factors listed in the IBS diary maintained by patients may yield important clues to an effective approach to diet and nutrition. One of the issues is that patients with IBS may have a lower threshold to stressors compared to people without IBS. An example of this is patients with carbohydrate intolerances as well as a diagnosis of IBS, who experience an even greater response to problematic carbohydrates such as lactose or fructose as compared to someone who does not have IBS. Another important issue is being alert to unnecessary food aversions. Individuals may experience abdominal discomfort and associate this with eating a certain food, so they decide to avoid eating that particular item, even for life. This may lead to excessive food restriction and the potential for a full-blown eating disorder. What must be kept in mind is that IBS is characterized by increased gut and central nervous system (CNS) reactivity to stressors, and that these stressors can include any dietary excesses as well as chain fatty acids. Good sources of soluble fiber include oats, psyllium seed, pectin, and guar gum. Insoluble fibers consist of the outer husk of the grain and generally tend to decrease transit time. The national nutrition guidelines recommend an intake of 20-30 grams of fiber per day, yet the typical American consumes less than 10 grams of fiber per day. Fiber intake should be increased gradually in IBS patients with constipation, with an emphasis on including adequate water consumption (5). The overall fiber picture can become a bit more confusing than a simple recommendation to increase fiber intake. Insoluble fiber may have a high content of cereal bran, which is the outer husk of the grain. A recent paper investigated the effects of adding or omitting bran and found conflicting results. It appears the primary care provider may see a greater benefit from patients adding fiber to their diet than the gastroenterologist, possibly because primary care physicians see mostly milder forms of IBS and gastroenterologists see patients with more severe IBS. Whorwell studied 100 patients in a primary care setting that were encouraged to increase cereal bran. The results in the primary care provider scenario produced a â€œmixedâ€ picture -- 22% reported worsening of IBS symptoms while 27% who showed improvement. This may be the result of visceral hypersensitivity triggered by bran consumption. Whorwell recommends that patients identified with IBS and visceral hypersensitivity should be counseled to exclude cereal (insoluble) fibers for a brief period to see if symptoms improve, especially if this is within the care of a specialty clinic. Another study found that cereal fibers were associated with a 55% worsening of symptoms (6, 7). Thus, if the goal is to increase transit rate and increase the frequency of bowel movements (for IBS-C), one could add insoluble fiber to the diet; however, since IBS is also associated with visceral hypersensitivity, if discomfort/pain or bloating occurs, the patient may need to switch solely to soluble fiber. Caffeine is a gastrointestinal stimulant. For IBS patients with diarrhea, a period of caffeine sensitivities to particular foods that are unique to the individual rather than to the IBS condition. This article reviews some of the literature in this area and then presents some treatment options to be considered in the nutritional management of IBS. It should be noted that the research and peer-reviewed published literature regarding IBS and diet is still very limited and, therefore, some of the resources cited in this article will date back several years. Nutritional Factors Influencing Motility: Fiber, Fat and Caffeine IBS is the most common of the functional GI disorder, affecting approximately 10-15% of the US population (1). IBS is a multifactorial illness with several different emerging pathophysiologies, including disorders of motility, visceral hypersensitivity, central processing dysfunctions, psychological factors, and post-infectious inflammation. Fiber: A recent survey reported that close to 95% of general practitioners believe that fiber deficiency is the main cause of IBS. In fact, the most common dietary advice offered to patients with IBS is for them to increase their intake of fiber, primarily to address the constipation that may be associated with IBS. However, since IBS is also associated with visceral hypersensitivity, luminal distension -- as might be caused by the bacterial fermentation of insoluble fiber -- can also produce discomfort (2). Dietary fiber is a non- starch polysaccharide derived from plant foods that are poorly digested by human enzymes. A fiber-enriched diet can relieve constipation, accelerate intestinal transit time, and may reduce intracolonic pressure. Furthermore, the intake of fiber is associated with a reduction in the intraluminal concentration of bile acids, which may reduce the contractile activity of the colon (3, 4). There are two types of fiber -- soluble and insoluble. Soluble fiber is derived from fruits and grains, and is fermented in the colon to form short exclusion may prove beneficial. The total intake of caffeine-containing beverages by many adults and children often reaches levels that can induce pharmacological effects. Evidence associating caffeine with GI symptoms suffered by patients with IBS is limited in the current literature, but one study revealed that caffeinated coffee stimulated colonic motor activity in a magnitude similar to that of an entire meal and had a 60% stronger effect than ingesting water (. Dietary fat is also a potent modulator of gut motor function. This macronutrient delays gastric emptying time and accelerates small bowel transit rates. Symptoms of bloating are commonly reported after consuming a high-fat meal. Serra et al. found that after an infusion of enteral fat, the volume of retained gas increased from 298 to 505 ml (9, 10). For patients who need to limit their fat intake, counting actual fat grams in the diet can be an excellent way to identify high-fat food sources. In general, IBS patients should aim for only 40-50 grams of fat per day. If weight loss becomes an issue with fat restriction, medium chain triglycerides (MCT) are an excellent source of calories. Unfortunately, MCT oils are expensive and, due to taste issues, are generally not wellreceived by patients. Food Allergy, Hypersensitivity and Intolerance Although up to 45% of the population reports adverse reactions to food, the actual prevalence of immune-mediated food allergy is unknown. Symptoms are more common in atopic individuals who often have allergies to non-food antigens as well, such as pollens, and in young children who tend to outgrow an allergy. The role of food allergy in IBS has not been studied well. Surveys indicate that 40-70% of food-allergic patients report GI symptoms including nausea, vomiting, abdominal pain, bloating, and diarrhea. Stefanini et al. conducted a 4-week multi-center study comparing the efficacy of the mast cell stabilizing agent sodium cromoglycate at 1500 mg per day with an elimination diet, and 67% of the patients reported improvement in their symptoms (11). Attempts to â€œtestâ€ for food hypersensitivity in IBS have largely focused on the classic food allergy, which is based on the presence of IgE -- immunoglobulins of the â€œimmediate typeâ€. These antibodies attach to certain cells in the body that release chemicals that cause anaphylaxis. Present speculation in the literature suggests that adverse reactions to food in patients with IBS might be due to forms of immunological mechanisms other than a dietary allergy, namely IgG antibodies. These tend to have a delayed response following exposure to a particular antigen and have been implicated in some cases of food hypersensitivity. IgG studies surfacing in the IBS literature are promising, but the issue of the validation of serum IgG testing is often raised. Atkinson et al. observed significant improvement in IBS symptoms in elimination diets using Elisa IgG antibody testing. Their results suggest that IgG antibodies may have a role in helping patients identify candidate foods for elimination (12). Collins et al. also found significant change in patients receiving the IgG exclusion diet. The foods that were most frequently associated with elevated IgG levels were yeast, milk, eggs, wheat, cashew nuts, peas, almonds, and barley. The mechanism by which the IgG antibodies have a detrimental effect is unclear, but most likely is associated with low-grade inflammation (12,13). For the most part, most patients with IBS do not have immune-mediated allergies to food and, more likely, have increased sensitivity to the direct effects of food on digestive function including increased food volume ingestion and the addition of fats, caffeine, carbohydrates, alcohol, etc. Food Intolerance and Exclusion Diets Niec recently summarized the literature on clinical trials using food elimination diets followed by rechallenge. Of the seven studies included in their review, positive response rates varied from 15 to 75 percent. A higher rate of response was correlated with diarrhea-predominant IBS. Milk, wheat and eggs were the most frequently implicated foods (14). Although the principle of food elimination or exclusion appears straightforward, it can be very demanding for the patient. If the patient appears hesitant or confused about food choices, physician referral to a registered dietitian may be helpful. With the exclusion of entire food groups, such as dairy products, the risk of developing a nutritional deficiency must be considered. Carbohydrate Malabsorption Carbohydrate intolerance can be seen in many patients with IBS. Fructose, lactose and sorbitol malabsorption are common among patients who have IBS, and dietary restriction of these sugars may improve symptoms (15,16). One study found that 42% of IBS patients developed symptoms from sorbitol-fructose mixtures compared to 3.5 % in the control group (1. This could be an important factor when patients are consuming large amounts of weight-loss products or have diarrhea-predominant IBS. Lactose malabsorption occurs when lactose, the primary sugar in dairy products, is not completely digested and absorbed in the small bowel. Lactase, the enzyme required to hydrolyze lactose for intestinal absorption, is found primarily in the tips of the jejunum. When unabsorbed lactose reaches the colon, colonic bacteria uses this substrate for fermentation, producing gas and short chain fatty acids. The unabsorbed lactose also affects osmolality, causing water to be drawn into the bowel and accelerating the intestinal transit time. If lactose intolerance is suspected, it can be confirmed with a hydrogen breath test. Lactose intolerance appears to be dose dependant. This means that many patients can tolerate small amounts of dairy products throughout the day, such as Â½ cup of milk, but not larger amounts. Although it may seem obvious which foods contain lactose, some sources may be difficult to discern. Patients should look for hidden sources in baked goods, salad dressings, and powdered mixes. Labels with the following words contain lactose: nonfat dry milk, milk powder, dry milk solids, whey curds, and caseinate milk sugar. Contrary to popular belief, acidophilus milk does not have the lactose sugar digested and is, therefore, a poor substitute for regular milk. Soymilk and rice milk do not contain lactose and are, therefore, good dairy substitutes. However, these products are often low in calcium and vitamin D. Hard cheeses and cultured yogurt are usually acceptable alternatives. For patients who do not tolerate lactose but want to consume dairy products, supplemental lactase enzymes are available. Several studies have shown that patients with lactose intolerance have significantly less calcium intake than those who tolerate lactose. In one study, patients who were lactose intolerant had a calcium intake of approximately 300 mg per day (1, which is only 20-40% of the recommended calcium intake for adults. Patients with lactose intolerance have also exhibited decreased bone mass density (19). In light of the potential for compromised calcium and vitamin D intake, it would be prudent to evaluate all patients with lactose intolerance for a calcium supplement if needed. Fructose is a hexose sugar that is highly utilized in the western diet. In the past 20 years, there has been a 10-fold increase due to its use in highly processed food products. It is often used as high fructose corn syrup in soda, fruit juices, cookies, baked goods, jellies, and candy. Unlike glucose, which is completely absorbed, fructose absorption capacity is limited. Therefore, when ingested in small quantities, dietary fructose will probably not be an issue. However, when consumed in larger amounts, fructose may serve to osmotically draw fluid into the intestinal lumen. This may cause distension of the small intestine and produce symptoms such as abdominal pain, bloating and discomfort. Furthermore, after reaching the colon, unabsorbed fructose may be fermented by colonic bacteria, producing excessive gas (20). Probiotics Several studies now exist defining the potential role of probiotics in IBS. These papers have exhibited a great degree of variability, possibly due to the use of different probiotic strains, their ability to adhere and colonize in the GI tract, and the number of colony-forming units actually ingested by the individual. The probiotics most often studied are lactobacillus, bidifobacterium, and some non-pathogenic forms of e-coli. In a recent study, bifidobacterium 35624 significantly alleviated symptoms of abdominal pain and discomfort, bloating, and distension. There was also a normalization of IL-10/IL-12 ratios (this skewed cytokine ratio may be indicative of a proinflammatory Th-1 state). The bifidobacterium used in this study is currently unavailable in the US marketplace in the concentrations used in this study (21,22). Food products that are high in probiotics include fermented milk, pourable yogurt, and yogurt with live active cultures. Currently, there is no federal agency in the US that routinely tests or â€œpolicesâ€ the market to ensure standardization and quality of probiotic products. Independent tests have revealed that up to 30% of probiotics on the market are â€œlacedâ€ with reasonably adequate live bacteria. One study used DNA extraction to test five probiotic products at a local health food store. The PCR analysis revealed that 2 of the 5 products did not contain the bifidobacterium claimed on the label (23). I called a well-known dairy in the Midwest several years ago. The technician responsible for mixing the probiotic in the yogurt explained that the bacteria are added to a very large vat of product. The yogurt is then packaged in individual cartons and there is no final definitive measurement to ensure that the amount of probiotic stated on the label is actually in each individual container. Putting It All Together Due to the complex underlying pathophysiologies in patients with IBS, nutritional intervention will vary with each patient. The following general IBS categories attempt to help â€œmapâ€ an approach for dietary manipulation in the patient with IBS. For individuals with diarrhea predominant IBS, consider limiting nutrients that exacerbate GI motility or intestinal secretion -- caffeine, fat and some carbohydrates (fructose, lactose and alcohol sugars). Probiotics can also be of benefit, especially if post-infectious IBS or bacterial overgrowth is suspected, or the patient has had numerous antibiotic therapies in the past. If constipation is the main issue, make sure the patient has had an adequate trial of increased insoluble fiber. This usually means that the patient needs to count fiber grams and seek to attain 20 grams of fiber per day. When visceral hypersensitivity is suspected, ask the patient to limit the amount of food eaten in one session and instead to eat three small meals per day with snacks. A low-fat diet and avoidance of insoluble fiber may also be helpful for these patients. Targeting nutritional intervention in the patient with IBS can be challenging due to the many different etiologies of this syndrome and the fact that some patients have heightened responses to different foods. A food diary kept by IBS patients can be a particularly helpful way to ascertain which foods may be problematic. It is recommended that the clinician look for food â€œtrendsâ€ in the journal, with the goal of steering the patient away from excessive food restriction behaviors. References Drossman DA, Camilleri M, Mayer EA, et al. AGA Technical Review on Irritable Bowel Syndrome. Gastroenterology 2002;123(6):2108-2131. Bijkerk CJ, de Wit NJ, Stalman WA, et al. Irritable Bowel Syndrome in Primary Care: the Patient and Doctors Views on Symptoms, Etiology, and Management. Can J Gastroenterology 2003;17(6):363-368. Muller-Lissner SA. Effect of Wheat Bran on Weight of Stool and Gastrointestinal Transit Time: A Meta Analysis. Br Med J 1988;296:615- 617. Villaneva A, Dominguez-Munoz J, Mearin F. Update in the Therapeutic Management of Irritable Bowel Syndrome. Dig Dis 2001;19:244-250. Floch MH, Narayan R. Diet in Irritable Bowel Syndrome. J Clin Gastroenterol 2002;35:S48. Francis CY, Whorwell P. Bran and Irritable Bowel Syndrome: Time for Reappraisal. Lancet 1994;344(8914):39-40. Lea R, M Bch B, Whorwell P. The Role of Food Intolerance in Irritable Bowel Syndrome. Gastroenterol Clin N Am 2005;34:247-255. Rao S, Welcher K, Zimmerman B, et al. Is Coffee a Colonic Stimulant? Eur J Gastroenterol Hepatol 1998;10:113-118. Serra J, Salvioli B, Azpiroz F, et al. Lipid Induced Intestinal Gas Retention in Irritable Bowel Syndrome. Gastroenterology 2002;123(3):700-706. Jones VA, McLaughlin P, Shorthouse M, et al. Food Intolerance: a Major Factor in the Pathogenesis of Irritable Bowel Syndrome. Lancet 1982;2(8308):1115-1117. Stefanini GF, Saggioro A, Alvisi V, et al. Oral Cromolyn Sodium in Comparison with Elimination Diet in Irritable Bowel Syndrome, Diarrheic Type. Muti Center Study of 428 patients. Scand J Gastroenterol 1995;30(6):535-541. Atkinson W, Sheldon T, Shaath N, et al. IgG Antibodies to Food: a Role in Irritable Bowel syndrome. Gut 2004;53: 1459-1464. Collins SM, Vallance B, Barabra G, et al. Putative Inflammatory and Immunological Mechanisms in Functional Bowel Disorders. Bailleres Best Pract Res Clin Gastroenterol 1999;13(3):429-436. Niec AM, Frankum B, Talley NJ. Are Adverse Food Reactions Linked to Irritable Bowel Syndrome? Am J Gastroenterol 1998;93(11):2184-2190. Fernadez-Banares F, Esteve-Pardo M, de Leon R, et al. Sugar Malabsorption in Functional Bowel Disease: Clinical Implications. Am J Gastroenterol 1993;88(12): 2044-2050. Nelis GF, Vermeeren MA, Jansen W. Role of Fructose-sorbitol Malabsorption in the Irritable Bowel Syndrome. Gastroenterology 1990; 99(4):1016-1020. Symons P, Jones MP, Kellow J. Symptom Provocation in Irritable Bowel Syndrome. Effects of Differing Doses of Fructose-sorbitol. Scand J Gastroenterol 1992;27:940-944. Carroccio A, Montalto G, Cavera G, et al. Lactose Intolerance and Selfreported Milk Intolerance: Relationship with Lactose Maldigestion and Nutrient Intake. Lactase Deficiency Study Group J Am Coll Nutr 1998;17:631-636. Di Stefano MD, Veneto G, Malservis S, et al. Lactose Malabsorption and Intolerance and Peak Bone Mass. Gastroenterology 2002;122:1793- 1799. Choi YK, Johlin F, Summers R, et al. Fructose Intolerance: An Underrecognized Problem. Am J Gastroenterol 2003;98:1348-1353. Oâ€™Sullivan MA, Oâ€™Morain CA. Bacterial Supplementation in the Irritable Bowel Syndrome. A Randomized Double-blind Placebo Controlled Crossover Study. Dig Liver Dis 2000;32(4):294-301. Mahoney L, McCarthy J, Kelly P, et al. Lactobacillus and Bifidobacterium in Irritable Bowel Syndrome: Symptom Responses and Relationship to Cytokine Profiles. Gastroenterology 2005; 128(3):541-551. Drisko J, Bischoff B, Giles C, et al. Evaluation of Five Probiotic Products for Label Claims by DNA Extraction and Polymerase Chain Reaction Analysis. Digestive Disease and Sciences 2005;50: 1113-1117. http://www.med.unc.edu/wrkunits/2depts/med...2005_digest.pdf


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## eric (Jul 8, 1999)

FYIDr Drossman's comments on foods for IBS Health.Shawn,To say that people with IBS may get symptoms from food intolerances is an acceptable possibility, since the gut will over react to stressors of all types including food (high fat or large volumes of food in particular). Futhermore, there can be specific intolerances. So if you have a lactose intolerance for example, it can exacerbate, or even mimic IBS. Other examples of food substances causing diarrhea would be high consumers of caffeine or alcohol which can stimulate intestinal secretion or with the latter, pull water into the bowel (osmotic diarrhea). The same would be true for overdoing certain poorly absorbed sugars that can cause an osmotic type of diarrhea Sorbitol, found in sugarless gum and sugar substituted foods can also produce such an osmotic diarrhea. Even more naturally, people who consume a large amount of fruits, juices or other processed foods enriched with fructose, can get diarrhea because it is not as easily absorbed by the bowel and goes to the colon where it pulls in water. So if you have IBS, all of these food items would make it worse. However, it is important to separate factors that worsen IBS (e.g., foods as above, stress, hormonal changes, etc.) from the cause or pathophysiology of IBS. Just like stress doesn't cause IBS, (though it can make it worse), foods must be understood as aggravating rather than etiological in nature. The cause of IBS is yet to be determined. However, modern research understands IBS as a disorder of increased reactivity of the bowel, visceral hypersensitivity and dysfunction of the brain-gut axis. There are subgroups being defined as well, including post-infectious IBS which can lead to IBS symptoms. Other work using brain imaging shows that the pain regulation center of the brain (cingulate cortex) can be impaired, as well as good evidence for there being abnormalities in motility which can at least in part explain the diarrhea and constipation. So finding a specific "cause" of IBS has grown out of general interest in place of understanding physiological subgroups that may become amenable to more specific treatments. Hope that helps.Doug http://www.ibshealth.com/ibs_foods_2.htmhttp://www.ibshealth.com/ibsfoodsinfo.htmDr Wood's comments for me"Dr. Jack Wood, a renowned physiologist at The Ohio State University calls the ENS â€œthe little-brain-in-the-gut.â€ "Dear Shawn:Sorry for the delayed reply to your question. I generally agree with Dr. Drosssmanâ€™s response. A subgroup of individuals when they become sensitized to specific molecules in certain foods respond to ingestion of the molecules with symptoms of cramping abdominal pain, fecal urgency and explosive watery diarrhea. These are also the primary symptoms of diarrhea-predominant IBS. Enteric mast cells, by mechanisms we donâ€™t understand, become sensitized to the food molecule and respond to its presence by releasing a signal to the brain-in-the-gut (ENS) which is interpreted as a threat. The ENS responds by â€œrunningâ€ a program which organizes secretion and motility into a behavior pattern of the bowel, which rapidly clears the threat from the lumen. Because to be effective secretion occurs in large volumes and the contractions that accomplish rapid propulsion are strong, running of the program has the side effects of diarrhea and cramping pain. Big brain input to mast cells during stress activates the mast cells to evoke the symptoms resulting from exposure of the mast cells to sensitizing food antigens. Aside from food allergens and mast cells, certain chemicals such as those in hot peppers, stimulate sensory nerves in the ENS and we are beginning to understand how this can also lead to food-related symptoms that might mimic or exacerbate IBS.Hope this helps,Jackie (Jack) D. Wood "You have two brains: one in your head and another in your gut. Dr. Jackie D. Wood is a renowned physiologist at The Ohio State University. He calls the second brain, "the-little-brain-in-the-gut." This enteric nervous system is part of the autonomic nervous system and contains over one hundred million neurons, which is as many as are in the spinal cord. This complex network of nerves lines the walls of the digestive tract form the esophagus all the way down to the colon. This little brain in the gut is connected to the big brain by the vagus nerves, bundles of nerve fibers running from the GI tract to the head. All neurotransmitters, such as serotonin that are found in the brain are also present in the gut.Dr Wood has discovered that this little-brain-in-the-gut has programs that are designed for our protection and which are very much like computer programs. They respond to perceived threats in the same way that the limbic system or the emotional brain does. So the threat of a gastrointestinal infection can activate the program that increases gut contractions in order to get rid of the infection. The symptoms are abdominal cramping and diarrhea. Dr. Wood has determined that a type of cell found in the body and the gut, called the mast cell, is a key to understanding the connection of the big brain in the head with the little-brain-in-the-gut. Mast cells are involved in defense of the body. In response to certain threats or triggers, such as pollen or infection, mast cells release chemicals, such as histamine, that help to fight off the invader. Histamine is one of the chemicals that causes the symptoms of an allergy or a cold. When an infection of the gut occurs, such as food poisoning or gastroenteritis, the mast cells of the gut release histamine. The little-brain-in-the-gut interprets the mast cell signal of histamine release as a threat and calls up a protective program designed to remove the threat â€" at the expense of symptoms: abdominal pain and diarrhea. The brain to mast cell connection has a direct clinical relevance for irritable bowel syndrome and other functional gastrointestinal syndromes. It implies a mechanism for linking allostasis and the good stress response to irritable states (e.g., abdominal pain and diarrhea) of the gut. Mast cells can be activated to release histamine in response to perceived psychological stress, whether the stressor or trigger is consciously perceived or not. So the end result is the same as if an infection activated the program in the-little-brain-in-the-gut: abdominal pain and diarrhea."http://www.parkviewpub.com/nuggets/n5.html


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## eric (Jul 8, 1999)

From Medscape GastroenterologyLiterature Review -- Select Topics in IBS and Chronic ConstipationLatest From the Literature in IBS and Chronic Constipation: September 2006Posted 09/07/2006Brian E. Lacy, MD, PhD IntroductionIn this second installment in our quarterly literature review series on topical issues in irritable bowel syndrome (IBS) and chronic constipation, 3 original research studies are reviewed. These reports describe new information regarding the pathophysiology of IBS, the role of alternative therapies in the treatment of IBS, and the treatment of constipation.""Lawal A, Kern M, Sidhu H, Hofmann C, Shaker R. Novel evidence for hypersensitivity of visceral sensory neural circuitry in irritable bowel syndrome patients. Gastroenterology. 2006;130:26-33.The pathophysiology of IBS involves multiple underlying factors, including abnormalities in visceral sensation, disturbances in gut motility, and differences in the central nervous system (CNS) processing of visceral pain.[1] Many investigators now believe that visceral hypersensitivity is the most important pathophysiologic abnormality in IBS patients. The mechanism that leads to visceral hypersensitivity in patients with IBS is unknown, although current theories postulate the presence of abnormal sensory receptors and sensory afferents, deficient descending modulating factors, and a hypervigilant CNS. This latter component has been demonstrated in studies using functional magnetic resonance imaging (fMRI) and positron emission tomography scans.[2,3] The end result is that IBS patients sense abdominal discomfort at lower levels than normal individuals and often misinterpret normal sensations as painful (allodynia).[4] This has been demonstrated in a number of studies that typically involve distending the lumen of the gastrointestinal tract with a balloon.[5] One concern is that these studies may be influenced by cognitive processes associated with perceived sensory stimulation. Stated another way, anticipation of a possibly unpleasant sensation (balloon distention of the rectum) may alter cortical activity and thus change fMRI findings. Lawal and colleagues[6] addressed this potentially confounding factor by evaluating visceral sensation in IBS patients using subliminal stimulation."The investigators used fMRI to quantitate cerebral cortical activity after rectal balloon distention. In contrast to other balloon distention studies, however, these investigators used subliminal balloon distention. Patients with IBS meeting Rome II criteria (age range, 19-38 years; all female) and age- and sex-matched volunteers were first evaluated to determine the perception threshold for balloon distention in each patient. Confirming findings from prior studies,[4,5] these authors again demonstrated that patients with IBS are more sensitive to balloon distention of the gastrointestinal tract than normal volunteers. Patients and volunteers then underwent balloon distention with subliminal pressures (10-20 mm Hg) while fMRI measurements were taken. Two scans were performed at each distention level. Cortical fMRI activity (quantitated by measuring cortical volume) was significantly greater in patients with IBS at all 3 levels of distention compared with volunteers. In volunteers, there was a direct relationship between stimulus intensity and cortical activity volume, with higher levels of subliminal intensity associated with increased cortical activity. However, this relationship was not present in IBS patients; high levels of cortical activity were identified at even the lowest level (10 mm Hg) of rectal distention.This well-designed, novel study is the first to show that very low levels of distention in the gastrointestinal tract, without any related cognitive processes typically associated with perceived distention, lead to increased CNS activity in IBS patients compared with healthy volunteers. In addition, patients with IBS demonstrated a maximum response to subliminal distention, as compared with the graded response seen in healthy volunteers. *These findings are important for a number of reasons. One, it confirms the now widely accepted view that the brain-gut axis is a critical component in IBS. Two, it emphasizes that hypersensitivity is a key underlying pathophysiologic mechanism in the generation of symptoms in IBS patients.* And finally, although not evaluated in this study, these findings point out that therapeutic options for patients with IBS should focus on treating both the hypersensitive gut and the hypersensitive CNS."http://www.medscape.com/viewarticle/544018_2IBS -- Review and What's NewAmy Foxx-Orenstein, DO, FACG, FACP Medscape General Medicine. 2006;8(3) Â©2006 MedscapePosted 07/26/2006Abstract and IntroductionAbstractIrritable bowel syndrome (IBS) is a highly prevalent gastrointestinal motility disorder broadly characterized by abdominal pain/discomfort associated with altered bowel habits. The chronic and bothersome nature of IBS symptoms often negatively affects patient quality of life and activity level and places a substantial economic burden on patients and the healthcare system. Advances in research have led to a greater understanding of the underlying pathophysiology of IBS, particularly regarding the role serotonin plays in the gastrointestinal tract; the development of stepwise, symptom-based diagnostic strategies that allow for a diagnosis of IBS to be made without the need for extensive laboratory testing; and the development of treatment options targeting underlying pathophysiologic mechanisms that provide relief of the multiple symptoms associated with IBS. This review highlights recent advances in research and discusses how these findings can be applied to daily clinical practice.IntroductionIBS -- a complex, multifaceted condition broadly characterized by abdominal pain/discomfort associated with altered bowel habits -- is among the most prevalent gastrointestinal (GI) motility disorders. Prevalence estimates for IBS range from 3% to 20%, with most estimates in North America ranging from 10% to 15%.[1-3] Women are affected by IBS more often than men (2:1 in the community setting and 3:1 to 4:1 in the tertiary care setting).[2] IBS-related symptoms are often chronic and bothersome, negatively affecting patient activities of daily living (eg, sleep, leisure time), social relationships, and productivity at work or school.[4-6] Patients with IBS typically score lower than population norms or those with other chronic GI and non-GI disorders on measures of quality of life.[7-10] IBS also puts a heavy economic burden on patients, employers, and the healthcare system, resulting in more than $10 billion in direct costs (eg, from office visits, medications) and $20 billion in indirect costs (eg, through work absenteeism and reduced productivity) each year.[11-14]Advances in research during the past several decades have provided insight into the underlying pathophysiology of IBS, particularly the role of serotonin in the GI tract; the development of stepwise, symptom-based diagnostic strategies; and the development of targeted treatment options. This review discusses recent advances in research and explores how these findings can be applied in the clinical practice setting.""The Science of IBSGiven the lack of definitive organic markers for IBS, the absence of a unifying hypothesis regarding its underlying pathophysiology is not surprising. Nevertheless, important advances in research made during the past 50 years have brought us closer than ever to understanding the numerous putative etiologic factors involved in this multifaceted disorder, including environmental factors, genetic links, previous infection, food intolerance, and abnormal serotonergic signaling in the GI tract.Environmental InfluencesAlthough a patient's psychological state may influence the way in which he or she presents, copes with illness, and responds to treatment, no evidence supports the theory that psychological disturbances are the cause of IBS.[39,40] The biopsychosocial model proposed by Engel takes into account the interplay between biologic, psychological, and social factors.[41] This model proposes that there is an underlying biologic predisposition for IBS that may be acted on by environmental factors and psychological stressors, which contribute to disease development, the patient's perception of illness, and impact on treatment outcomes.[42,43]Studies evaluating the role of acute stress have shown that stress can result in release of stress-related hormones that affect colonic sensorimotor function (eg, corticotropin-releasing factor [CRF] and inflammatory mediators [eg, interleukin (IL)-1]), leading to inflammation and altering GI motility and sensation.[44] For example, CRF-1 receptors located in the central nervous system (CNS) and gut can affect colonic motility, epithelial water transport, and gut permeability.[45] Sagami and colleagues[46] determined that the peripheral administration of a nonselective corticotropin-releasing hormone (CRH) receptor antagonist improved GI motility, visceral perception, and negative mood in response to gut stimulation in patients with IBS. These findings suggest that CRH may play an important role in the pathophysiology of IBS.GeneticsStudies with twins have shown that IBS is twice as prevalent in monozygotic twins as in dizygotic twins.[47-49] Limited research on familial aggregation has found that individuals who have a family member (other than a spouse) with a history of abdominal pain or bowel disorder have more than 2-fold increased odds of having IBS. It is likely that environmental influences may help explain this finding (eg, awareness of the symptom status of family members may make sufferers more open to discussing their symptoms and seeking help for the condition).[50] Preliminary findings also suggest that IBS may be associated with select gene polymorphisms, including those in IL-10, G-protein GNb3, alpha adrenoceptor, and serotonin reuptake transporter (SERT).[47, 51-54] Despite these potential links, however, conclusive evidence for a genetic basis for IBS has not been established.Postinfectious IBSThe presence of postinfectious (PI)-IBS, referring to the development of IBS symptoms -- particularly abdominal pain and diarrhea -- shortly after an enteric infection, is based on research from prospective studies in which IBS symptoms developed in 7% to 32% of patients after they recovered from bacterial gastroenteritis.[52,55,56] Specific risk factors for the development of PI-IBS have been identified, including younger age, female sex, presence of severe infectious gastroenteritis for a prolonged period, use of antibiotics to treat this infection, and presence of concomitant psychological disorders (eg, anxiety).[39,52,55,57] Difficulty in downregulating intestinal inflammation in the colonic mucosa has been suggested as a potential underlying mechanism in this condition.[52] Also suggested as a potential underlying mechanism is the presence of colonic changes shown in patients with PI-IBS compared with controls, including increased gut permeability, increased mucosal enterochromaffin cell production, and increased concentration of mast cells and T lymphocytes in the gut mucosa.[39,52,55,57] Despite considerable evidence linking IBS with an inflammatory etiology (perhaps triggered by enteric infection), in a controlled trial of patients with PI-IBS, anti-inflammatory treatment with prednisolone was not more effective than placebo in improving patient symptoms.[58] The true role of prior infection as a key factor in PI-IBS remains to be established.[59]The use of probiotics (products containing live or attenuated bacteria that have a positive effect on the host) in alleviating symptoms in patients with PI-IBS is an area of recent focus.[60,61] The potential utility of probiotics in this setting stems from their antibacterial, antiviral, and immune-modulating properties; their ability to modify intestinal flora; and their potential to enhance intestinal mucus secretion or influence stool consistency or volume and gas handling.[60] The number of studies evaluating the efficacy of probiotic preparations in patients with IBS is limited but growing.[60-68] Because trials vary in study design, dose, and strain (Lactobacillus and Bifidobacteria alone or in combination; mixture of Lactobacillus, Bifidobacteria, and Streptococcus), direct comparison of results is challenging. Overall, some degree of IBS symptom improvement has been demonstrated in symptoms such as abdominal pain,[65,66] bloating,[63,66] gas,[66] and daily symptom scores.[62,65] O'Mahoney and colleagues[60] have recently demonstrated that results with the Bifidobacterium infantis strain are particularly promising. In a separate analysis, these investigators showed that the baseline characteristics of urgency and hard stool increased the odds ratio of response to this strain, whereas straining and alcohol consumption reduced the likelihood of response.[69,70] The ultimate place in therapy of probiotics in IBS remains to be elucidated.Small Intestinal Bacterial OvergrowthThe presence of a higher than usual population of bacteria in the small intestine (leading to bacterial fermentation of poorly digestible starches and subsequent gas production) has been proposed as a potential etiologic factor in IBS.[71] Pimentel and colleagues have shown that, when measured by the lactose hydrogen breath test (LHBT), small intestinal bacterial overgrowth (SIBO) has been detected in 78% to 84% of patients with IBS.[71,72] However, the accuracy of the LHBT in testing for the presence of SIBO has been questioned.[73] Sensitivity of the LHBT for SIBO has been shown to be as low as 16.7%, and specificity approximately 70%.[74] Additionally, this test may suboptimally assess treatment response.[75] The glucose breath test has been shown to be a more reliable tool,[76] with a 75% sensitivity for SIBO[77] vs 39% with LHBT for the "double-peak" method of SIBO detection.[74] In a recently conducted retrospective study involving review of patient charts for the presence of gastrointestinal-related symptoms (including IBS) in patients who were referred for glucose hydrogen breath tests for SIBO, of 113 patients who met Rome II criteria for IBS, 11% tested positive for SIBO.[78] Thus, results demonstrated that IBS symptoms are often unrelated to the presence of SIBO. Despite the controversy regarding the contribution of SIBO to the underlying pathophysiology of IBS and its symptoms, short-term placebo-controlled clinical studies with select antibiotics, including neomycin and rifaximin, have demonstrated symptom improvement in IBS patients.[61,72,79] Antibiotics may therefore have potential utility in select subgroups of IBS patients in whom SIBO contributes to symptoms. However, the chronic nature of IBS symptoms often leads to the need for long-term treatment. Given the fact that long-term use of antibiotics is generally undesirable, the place of antibiotics in IBS therapy remains to be established.[73]Food IntoleranceFood intolerance has been proposed as a potential cause of GI symptoms in some patients with IBS; however, this link is not well established. Although some patients associate onset of IBS symptoms with ingestion of particular foods, identification of a true food intolerance is challenging, and elimination diets are typically time-consuming and difficult to implement. Recent research involving exclusion of foods to which patients had immunoglobulin (Ig) G antibodies, which are associated with a more delayed response after antigen exposure than IgE antibodies, resulted in significantly better symptom improvement than in patients in the nonexclusion group.[80] Further research into the role of food intolerance in IBS is warranted.Serotonin SignalingOf the putative mechanisms underlying the pathophysiology of IBS, the strongest evidence points to the role of serotonin in the GI tract. The effect of serotonergic mechanisms in the manifestation of IBS symptoms has led to development of a new drug class for the treatment of IBS patients: the GI serotonergic agents.Normal GI function relies on a properly functioning brain-gut axis, which involves the coordinated interplay of the GI musculature, the CNS, the autonomic nervous system, and the enteric nervous system (ENS). The ENS contains millions of neurons embedded in the wall of the digestive tract and functions, at least in part, independently of the CNS. The size, complexity, and independent function of the ENS has resulted in application of the terms "the second brain" and "the mini-brain."[81] Impaired function or coordination of any of these systems, or the communication between these systems and the GI musculature, can lead to symptoms of dysmotility and altered sensory perception, which are characteristic of IBS and select other GI motility disorders.[82]The neurotransmitter serotonin (5-hydroxytryptamine [5-HT]) is a predominant signaling molecule in the ENS. Most (90% to 95%) of the body's serotonin is found in the gut, and smaller amounts are found in the brain (about 3%) and in platelets (about 2%).[83] In the GI tract, serotonin facilitates communication between the ENS and its effector systems (muscles, secretory endothelium, endocrine cells, and vasculature of the GI tract), thus playing a key role in normal GI tract functioning.[84] In addition, serotonin plays a role in the communication between the ENS and the CNS.In the gut, serotonin is synthesized by and stored in the enterochromaffin cells, which are located within the mucosa of the intestinal wall. When material passes through the lumen and the mucosa is stimulated, enterochromaffin cells release serotonin, which then binds to its receptors (primarily 5-HT1P receptors) on intrinsic primary afferent neurons, initiating peristalsis and secretion. Serotonin also binds to 5-HT4 receptors on interneurons, which augments the transmission of signals to motor neurons, resulting in enhanced peristaltic activity. In transgenic mice lacking 5-HT4 receptors, colonic motility is abnormally slow, confirming the role of these receptors in facilitating normal colonic motility.[85] By binding to 5-HT3 receptors on efferent sensory innervations coming from the vagus and the spinal nerves, serotonin mediates signaling between the ENS and the CNS and, thus, modulates pain perception.To regulate the signaling process, excess serotonin must be removed; this is accomplished by the SERT molecule expressed by intestinal epithelial cells.[86] Human studies have shown that defects in serotonin signaling contribute to the pathophysiology of IBS and, potentially, other GI motility disorders. In a recent study by Coates and colleagues,[87] biopsy specimens from patients with IBS showed significantly lower mucosal serotonin concentrations than those from healthy controls, potentially the result of lower mRNA levels for tryptophan hydroxylase (the rate-limiting enzyme in serotonin synthesis), which were also significantly lower in patients with inflammatory bowel disease.[87] There was no significant difference in the number of enterochromaffin cells or in the capacity of these cells to release serotonin under stimulated conditions. In another study, higher serotonin levels were observed in mucosal biopsy samples from patients with IBS with constipation (IBS-C) than in patients with IBS-D or in healthy volunteers.[88]Serotonin levels may also be affected by altering the amount or function of SERT. The study by Coates and colleagues[87] showed a significant decrease in the level of SERT mRNA and SERT protein expressed in the intestinal epithelial cells of IBS patients compared with that of healthy volunteers. In another study,[89] SERT expression and binding capacity in platelets were decreased in women with IBS-D compared with expression and binding capacity in healthy controls. Furthermore, Chen and colleagues[90] showed that mice with a SERT gene deletion had altered colonic motility. It is interesting to note that the mice thrived in laboratory housing conditions, indicating that other transporters could compensate for the lack of SERT. Additional studies have focused on SERT polymorphisms. Yeo and colleagues[91] showed an association between patients with IBS-D and the homozygous short polymorphism of the SERT gene promoter. This mutation results in lower levels of SERT gene transcription and reduced amounts of SERT protein available for reuptake of serotonin. In addition, Camilleri and colleagues[92] showed a possible link between the long promoter polymorphism and patient response to therapy.Thus, a substantially large body of work shows that normal gut physiology is predicated on the interplay between the GI musculature and the ENS, autonomic nervous system, and CNS. One of the central mediators of this complex interplay is the neurotransmitter serotonin. Impairment or imbalance in serotonergic signaling, which can affect GI motility, secretion, and visceral sensitivity, may be affected by defects or deficiencies in serotonin production, specific serotonin receptors, or proteins such as SERT. These changes can manifest in symptoms associated with IBS, including abdominal pain, altered bowel habits (constipation, diarrhea, or alternation between these 2 states), and bloating."http://www.medscape.com/viewarticle/532089_print


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