The importance of probiotics in the prevention and treatment of selected lifestyle diseases

Irritable bowel syndrome (IBS) and chronic idiopathic constipation ((CIC) also referred to as functional constipation) are two of the most common functional gastrointestinal disorders worldwide. IBS is a global problem, with anywhere from 5 to 15% of the general population experiencing symptoms that would satisfy a definition of IBS (1,2). In a systematic review on the global prevalence of IBS, Lovell and Ford (1) documented a pooled prevalence of 11% with all regions of the world suffering from this disorder at similar rates. Given its prevalence, the frequency of symptoms, and their associated debility for many patients and the fact that IBS typically occurs in younger adulthood, an important period for furthering education, embarking on careers, and/or raising families, the socioeconomic impact of IBS is considerable. These indirect medical costs are frequently compounded by the direct medical costs related to additional medical tests and the use of various medical and nonmedical remedies that may have limited impact. CIC is equally common; in another systematic review, Suares and Ford (3) reported a pooled prevalence of 14%, and also noted that constipation was more common in females, in older subjects, and those of lower socioeconomic status (3). Chronic constipation has also been linked to impaired quality of life (4), most notably among the elderly (5). Neither IBS nor CIC are associated with abnormal radiologic or endoscopic abnormalities, nor are they associated with a reliable biomarker; diagnosis currently rests entirely, therefore, on clinical grounds. Although a number of clinical definitions of both IBS and CIC have been proposed, the criteria developed through the Rome process, currently in its third iteration, have been those most widely employed in clinical trials and, therefore, most relevant to any review of the literature on the management of these disorders. According to Rome III, IBS is defined on the basis of the presence of: Recurrent abdominal pain or discomfort at least 3 days/month in the past 3 months associated with two or more of the following: Improvement with defecation Onset associated with a change in frequency of stool Onset associated with a change in form (appearance) of stool These criteria should be fulfilled for the past 3 months with symptom onset at least 6 months before diagnosis (6). Rome III defines functional constipation as: the presence of two or more of the following: Straining during at least 25% of defecations Lumpy or hard stools in at least 25% of defecations Sensation of incomplete evacuation for at least 25% of defecations Sensation of anorectal obstruction/blockage for at least 25% of defecations Manual maneuvers to facilitate at least 25% of defecations (e.g., digital evacuation, support of the pelvic floor) Fewer than three defecations per week Furthermore, loose stools are rarely present without the use of laxatives and there are insufficient criteria for IBS. Again, these criteria should be fulfilled for the past 3 months with symptom onset at least 6 months before diagnosis (6). In Rome III, IBS is subtyped according to predominant bowel habit as IBS with constipation (IBS-C), IBS with diarrhea (IBS-D), mixed type (IBS-M), and unclassified (IBS-U). The definition of bowel habit type is, in turn, based on the patient's description of stool form by referring to the Bristol Stool Scale (7). The recognition that IBS sufferers segregate into subtypes according to predominant bowel habit, together with research findings suggesting that IBS-C and IBS-D may be pathophysiologically distinct entities (8,9,10), led to the development of therapies specifically directed at each of these subtypes. Nonetheless, it is worth noting that symptoms may not be stable over a lifetime and individuals may exhibit one IBS subtype during a period, and then a different IBS subtype during another period in their lives. However, although there is general awareness of the Rome criteria, they are infrequently employed in the assessment of IBS and CIC in clinical practice (11). To provide more "clinician friendly" definitions, as well as to permit inclusion of studies that predated the Rome process, American College of Gastroenterology Task Forces suggested the following definitions in prior systematic reviews: IBS is defined by: abdominal discomfort associated with altered bowel habits (12). Constipation is defined as: a symptom-based disorder defined as unsatisfactory defecation and is characterized by infrequent stools, difficult stool passage, or both. Difficult stool passage includes straining, a sense of difficulty passing stool, incomplete evacuation, hard/lumpy stools, prolonged time to stool, or need for manual maneuvers to pass stool. CIC is defined as the presence of these symptoms for at least 3 months (13). It is important to note that the Rome III criteria state that individuals with chronic constipation do not fulfill criteria for IBS, with pain or discomfort being a major determinant in the latter. In practice, a clear separation between CIC and IBS with constipation may be challenging and studies have shown, not only considerable overlap between these entities (14,15,16), but also a significant tendency for patients to migrate between these diagnoses over time (15). It is appropriate therefore that in this update of prior American College of Gastroenterology monographs on IBS and CIC, these entities be addressed in the same exercise (12,13,17). The goal of this exercise, therefore, was to update the most recent systematic reviews commissioned by the American College of Gastroenterology on IBS from 2009 (17) and CIC from 2005 (13). METHODS We have conducted a series of systematic reviews on the efficacy of therapy in IBS and CIC. There have been several systematic reviews of therapy for IBS and CIC published in the past 5 years (18,19,20,21,22). There have been considerable data published in the intervening time, and hence we have, therefore, updated all these systematic reviews of IBS and CIC and synthesized the data, including the information from new trials, where appropriate. The primary objective of this exercise was to assess the efficacy of available therapies in treating IBS and CIC compared with placebo or no treatment. The secondary objectives included assessing the efficacy of available therapies in treating IBS according to predominant stool pattern reported (IBS with constipation, IBS with diarrhea, and mixed IBS), as well as assessing adverse events with therapies for both IBS and CIC. Systematic review methodology We evaluated manuscripts that studied adults (aged >16 years) using any definition of IBS or CIC. For IBS, this included a clinician-defined diagnosis, the Manning criteria (23), the Kruis score (24), or Rome I (25), II (26), or III (6) criteria. For CIC, this included symptoms diagnosed by any of the Rome criteria (6,25,26), as well as a clinician-defined diagnosis. We included only parallel-group randomized controlled trials (RCTs) comparing active intervention with either placebo or no therapy. Crossover trials were eligible for inclusion, provided extractable data were provided at the end of the first treatment period, before crossover. For IBS, the following treatments were considered: Diet and dietary manipulation Fiber Interventions that modify the microbiota: probiotics, prebiotics, antibiotics Antispasmodics Peppermint oil Loperamide Antidepressants Psychological therapies, including hypnotherapy Serotonergic agents Prosecretory agents Polyethylene glycol For CIC, the following were considered: Fiber Osmotic and stimulant laxatives 5-HT4 agonists Prosecretory agents Biofeedback Bile acid transporter inhibitors Probiotics Subjects needed to be followed up for at least 1 week. To be eligible, trials needed to include one or more of the following outcome measures: Global assessment of improvement in IBS or CIC symptoms Improvement in abdominal pain for IBS Global IBS symptom or abdominal pain scores for IBS Mean number of stools per week during therapy for CIC Search strategy for identification of studies MEDLINE (1946 to October 2013), EMBASE and EMBASE Classic (1947 to October 2013), and the Cochrane central register of controlled trials were searched. Studies on IBS were identified with the terms irritable bowel syndrome and functional diseases, colon (both as medical subject headings (MeSH) and free text terms), and IBS, spastic colon, irritable colon, and functional adj5 bowel (as free text terms). For RCTs of dietary manipulation, these were combined using the set operator AND with studies identified with the terms: diet, fat-restricted, diet, protein-restricted, diet, carbohydrate-restricted, diet, gluten-free, diet, macrobiotic, diet, vegetarian, diet, Mediterranean, diet fads, gluten, fructose, lactose intolerance, or lactose (both as MeSH and free text terms), or the following free text terms: FODMAP$, glutens, food adj5 intolerance, food allergy, or food hypersensitivity. For RCTs of fiber, antispasmodics, and peppermint oil, these were combined using the set operator AND with studies identified with the terms: dietary fiber, cereals, psyllium, methylcellulose, sterculia, karaya gum, parasympatholytics, hyoscyamine, scopolamine, trimebutine, muscarinic antagonists, or butylscopolammonium bromide (both as MeSH and free text terms), or the following free text terms: bulking agent, psyllium fiber, fiber, husk, bran, ispaghula, wheat bran, calcium polycarbophil, spasmolytics, spasmolytic agents, antispasmodics, mebeverine, alverine, pinaverium bromide, otilonium bromide, cimetropium bromide, hyoscine butyl bromide, butylscopolamine, peppermint oil, or colpermin. For RCTs of probiotics, these were combined using the set operator AND with studies identified with the terms: Saccharomyces, Lactobacillus, Bifidobacterium, Escherichia coli, or probiotics (both as MeSH and free text terms). For RCTs of prebiotics and synbiotics, these were combined using the set operator AND with studies identified with the term: prebiotic (both MeSH and free text terms) or synbiotic (both MeSH and free text terms). For RCTs of antibiotics, these were combined using the set operator AND with studies identified with the terms: anti-bacterial agents, penicillins, cephalosporins, rifamycins, quinolones, nitroimidazoles, tetracycline, doxycycline, amoxicillin, ciprofloxacin, metronidazole, or tinidazole (both as MeSH and free text terms), or the following free text terms: antibiotic or rifamixin. For RCTs of loperamide, these were combined using the set operator AND with studies identified with the terms: loperamide or antidiarrheals (both as MeSH and free text terms), or the following free text terms: imodium or lopex. For RCTs of antidepressants and psychological therapies, including hypnotherapy, these were combined using the set operator AND with studies identified with the terms: psychotropic drugs, antidepressive agents, antidepressive agents (tricyclic), desipramine, imipramine, trimipramine, doxepin, dothiepin, nortriptyline, amitriptyline, selective serotonin reuptake inhibitors, paroxetine, sertraline, fluoxetine, citalopram, venlafaxine, cognitive therapy, psychotherapy, behavior therapy, relaxation techniques, or hypnosis (both as MeSH and free text terms), or the following free text terms: behavioral therapy, relaxation therapy, or hypnotherapy. For RCTs of serotonergic agents, these were combined using the set operator AND with studies identified with the terms: serotonin antagonists, serotonin agonists, cisapride, receptors (serotonin, 5-HT3), or receptors (serotonin, 5-HT4) (both as MeSH and free text terms), or the following free text terms: 5-HT3, 5-HT4, alosetron, cilansetron, ramosetron, prucalopride, mosapride, or renzapride. For RCTs of pro-secretory agents, these were combined using the set operator AND with studies identified with the following free text terms: linaclotide or lubiprostone. For RCTs of polyethylene glycol (PEG), these were combined using the set operator AND with studies identified with the term polyethylene glycol (both as a MeSH and free text term). Studies on CIC were identified with the terms constipation or gastrointestinal transit (both as MeSH and free text terms), or functional constipation, idiopathic constipation, chronic constipation, or slow transit (as free text terms). For the search involving biofeedback, the free text terms dyssynergia, pelvic floor dysfunction, anismus, and outlet obstruction were also added. For RCTs of fiber, these were combined using the set operator AND with studies identified with the terms: dietary fiber, cellulose, plant extracts, psyllium, cereals, plantago, or methylcellulose (both as MeSH and free text terms), or the following free text terms: fiber, soluble fiber, insoluble fiber, bran, ispaghula, metamucil, fybogel, or ispaghula. For RCTs of osmotic and stimulant laxatives, these were combined using the set operator AND with studies identified with the terms: laxatives, cathartics, anthraquinones, phenolphthaleins, indoles, phenols, lactulose, polyethylene glycol, senna plant, senna extract, bisacodyl, phosphates, dioctyl sulfosuccinic acid, magnesium, magnesium hydroxide, sorbitol, poloxamer (both as MeSH and free text terms), or the following free text terms: sodium picosulphate, docusate, milk of magnesia, danthron, senna, and poloxalkol. For RCTs of 5-HT4 agonists, these were combined using the set operator AND with studies identified with the terms: serotonin agonists, receptors, or serotonin, 5-HT4 (both as MeSH and free text terms), or the following free text terms: prucalopride, velusetrag, or naronapride. For RCTs of pro-secretory agents, these were combined using the set operator AND with studies identified with the following free text terms: lubiprostone or linaclotide. For RCTs of biofeedback, these were combined using the set operator AND with studies identified with the MESH terms biofeedback and psychology and the following free text terms: biofeedback or neuromuscular training. For RCTs of bile acid transporter inhibitors, these were combined using the set operator AND with studies identified with the following free text terms: bile acid transporter, elobixibat, or A3309. For RCTs of probiotics, these were combined using the set operator AND with studies identified with the terms: Saccharomyces, Lactobacillus, Bifidobacterium, E. coli, or probiotics (both as MeSH and free text terms). For RCTs of prebiotics and synbiotics, these were combined using the set operator AND with studies identified with the term: prebiotic (both MESH and free text terms) or synbiotic (both MESH and free text terms). The search was limited to humans. No restrictions were applied with regard to language of publication. A recursive search of the bibliography of relevant articles was also conducted. DDW (Digestive Diseases Week) and UEGW (United European Gastroenterology Week) abstract books were hand searched between 2000 and 2013. Authors of trial reports that did not give enough detail for adequate data extraction were contacted and asked to contribute full data sets. Experts in the field were contacted for leads on unpublished studies. Trials were assessed for risk of bias according to the methods described in the Cochrane handbook [27] using the following characteristics: method used to generate the randomization schedule, method used to conceal treatment allocation, implementation of masking, completeness of follow-up, and conduct of an intention-to-treat analysis. Eligibility, quality, and outcome data were extracted by the lead reviewer (Alexander Ford) and by a masked second reviewer (Paul Moayyedi) on to specially developed forms. Any discrepancy was resolved by discussion between the two reviewers in order to reach a consensus. Data were extracted as intention-to-treat analyses, where all dropouts were assumed to be treatment failures, wherever trial reporting allowed this. Data synthesis For IBS, whenever possible, any improvement of global IBS symptoms as a binary outcome was taken as the primary outcome measure. If this was not available, improvement in abdominal pain was used. For CIC, any improvement of global CIC symptoms as a binary outcome was taken as the primary outcome measure. The impact of interventions was expressed as a relative risk (RR) of IBS or CIC symptoms not improving, together with 95% confidence intervals (CIs). If there were sufficient data, RRs were combined using the DerSimonian and Laird random effects model (28) to give a more conservative estimate of the efficacy of individual IBS therapies. For continuous data, such as global IBS symptom scores or individual IBS symptom scores, a standardized mean difference, with 95% CIs, was calculated. It should be noted that some treatments may be beneficial in IBS or CIC because of the effects on outcomes other than global symptoms or abdominal pain, but this was not evaluated and was outside of the scope of this review. Tests of heterogeneity were reported (29). When the test of heterogeneity was significant (P<0.10 and/or I2>25%), the reasons for this were explored by evaluating differences in study population, study design, or study end points in subgroup analyses. Publication bias or other causes of small study effects were evaluated using tests for funnel plot asymmetry (30), where sufficient studies were identified (31). The number needed to treat (NNT), which is the number of patients who would need to receive active therapy, over and above the control therapy, for one to experience an improvement in symptoms, and the number needed to harm (NNH), which is the number of patients who would need to receive active therapy, over and above the control therapy, for one to experience an adverse event were calculated as the inverse of the risk difference from the meta-analysis and checked using the formula: NNT = 100 / RRR × BR, where BR is baseline risk and RRR is relative risk reduction. Methodology for assessing levels of evidence and grading recommendations We used the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system for grading the quality of evidence and strength of recommendation for each medical intervention (32). The system has been widely used in evidence-based guidelines and is endorsed by all major gastrointestinal societies (http://www.gradeworkinggroup.org). The quality of the evidence is based on the study design, as well as the extent of risk of bias, inconsistency, indirectness, imprecision, and publication bias that exists for the evidence supporting the intervention (33). Quality of evidence is described as high to very low, depending on the extent to which further evidence would change the estimate of treatment effect (Box 1). The grading scheme also classifies recommendations as strong or weak, according to the quality of the evidence, applicability to all patient groups, balance of benefits and risks, patient preferences, and cost. With this graded recommendation, the clinician receives guidance about whether or not recommendations should be applied to most patients, and whether or not recommendations are likely to change in the future after production of new evidence. "Strong" recommendations represent a "recommendation that can apply to most patients in most circumstances and further evidence is unlikely to change our confidence in the estimate of treatment effect." The summary of the evidence for IBS is presented in Table 1, the reasons for the decision on the quality of that evidence in Table 2, and the reasons for the strength of recommendation in Table 3. Similarly, the summary of the evidence for CIC is presented in Table 4, the reasons for the decision on quality of the evidence in Table 5, and the reasons for the strength of recommendation in Table 6.Box 1.: Interpretation of the grading of the quality of evidenceTable 1: Summary of results of monograph on interventions for IBSTable 2: Reasons for quality of evidence of assessment for IBS data according to GRADE criteriaTable 2: Continued.Table 3: Reasons for strength of recommendation for IBS therapies according to GRADE criteriaTable 4: Summary of results of monograph on interventions for CICTable 5: Reasons for quality of evidence of assessment of data on CIC according to GRADE criteriaTable 6: Reasons for strength of recommendation for treatments of CIC according to GRADE criteriaRESULTS Irritable bowel syndrome 1. Diet and dietary manipulation in IBS (a) Role of diet in IBS: Although food intake is one of the most common precipitants of symptoms in IBS (34), responses to food and with of the diet have not typically in the of a on their IBS sufferers have their to this or guidance from dietary IBS patients that they have an to although food are in IBS although the prevalence of food in societies is between 1 and in of gastrointestinal patients that that their symptoms food or food IBS symptoms to represent food intolerance, although only of patients can the food in a on their with and a of objective evidence to a studies have that a of IBS patients dietary to an extent that may their Role of dietary manipulation in may symptoms in individual IBS Quality of very We identified RCTs that evaluated dietary intervention in IBS to data of relevant symptom data and an intervention week three RCTs involving patients The first of these addressed the impact of in IBS. In a patients with IBS were randomized to either on a diet or to receive of on of an In the reported that their symptoms were not controlled as compared with in the placebo symptom scores for abdominal pain, with stool and were in those who a The second of these studies the of food or as not by but by In a parallel-group IBS patients were randomized to either an diet based on the presence of to various or a were followed for and symptoms assessed using a global impact score and the IBS with in the diet in the diet intervention noted a significant improvement in The reported in those with high to their The third study the of and IBS patients were randomized to a diet or their diet for those randomized to the diet, reported adequate control of their symptoms compared with of the diet Stool did not between stool frequency was in the diet A significant of this study was the of the dietary the of dietary in the of symptoms, or in the of IBS, is being To two and have been addressed in clinical trials, although it is that other (e.g., of and with the may also be relevant to the effects of food or food the that any of the of an diet or of a food in IBS the data provide limited guidance on the of diet in the management of IBS. and but their in the management of IBS need to be Fiber in IBS Fiber symptom in IBS. Quality of but not bran, symptom in IBS. Quality of intake of dietary is frequently to bowel for IBS, for However, insoluble frequently and abdominal In our prior systematic review we identified two additional studies for a of RCTs involving but trials did not IBS by subtype and only two to IBS-C In the study to patients, of were IBS-C and were were randomized to one of three of the soluble psyllium, of the insoluble bran, or of a placebo for the first a of patients psyllium, but not bran, reported adequate symptom for at least compared with placebo psyllium 95% was more than placebo during the third of treatment only 3 months of symptom in the psyllium was by points compared with points in the placebo and points in the No differences were with to quality of was most common in the most because of in IBS. Data on adverse events were only provided by trials These trials evaluated patients, but as of adverse events were small in 5 of the trials, of data was not A of of patients reported adverse events compared with of in the placebo Although its use in the management of IBS is time the status of fiber, in in IBS, is from may symptoms and provide soluble and psyllium, in provide in IBS. These effects to benefits in terms of of 3. Interventions that modify the microbiota: probiotics, prebiotics, and antibiotics The that the be relevant to IBS first from the that a although of individuals who an of on to IBS IBS Although has been linked to and and in the have been described in IBS, the of the to or other symptoms in IBS, is although both small and and in the have also been linked to IBS the of to IBS and findings in to the in patient probiotics, and have been used for on an basis by IBS they have only been to in clinical The of studies in IBS challenging as studies have employed different and in various patient and in Although the suggested that more than of all IBS sufferers studies have, in to such a high prevalence of in IBS These results may to to the test that may provide an of the this provided a for assessing antibiotics in IBS. a has efficacy in clinical trials in and although significant were over placebo in global IBS symptoms as well as in it is important to note that tests for were not in these trials, the of of in IBS (a) and in IBS: There is insufficient evidence to prebiotics or in IBS. Quality of very Probiotics in as a probiotics global symptoms, and in IBS.

Probiotics in irritable bowel syndrome: Has the time arrived?

Manipulation of the Microbiota for Treatment of IBS and IBD—Challenges and Controversies

Lactulose breath testing, bacterial overgrowth, and IBS: just a lot of hot air?

Bugs, Stool, and the Irritable Bowel Syndrome: Too Much Is as Bad as Too Little?

The pathogenesis of functional GI disorders (FGIDs) is uncertain. However, underlying immune activation and psychological distress has been documented in irritable bowel syndrome (IBS) and functional dyspepsia (FD). Epidemiological data from the UK suggest that FGIDs are linked to atopy and certain autoimmune diseases but this has not been confirmed. To test if allergic or autoimmune diseases are independently associated with FGIDs, irrespective of psychological distress in a large population based study. A total of 3542 people (mean age 57.9years and 52.7% females) randomly selected from the Australian population, returned a mail survey (response rate=43%). The survey asked about a physician diagnosis of autoimmune disease (scleroderma, psoriasis, rheumatoid arthritis and diabetes mellitus) or allergic conditions (asthma, food, pollen and/or animal allergy). The questionnaire assessed psychological distress and Rome III criteria for FD and IBS. Asthma, food, pollen and animal allergies, psoriasis and rheumatoid arthritis were univariately significantly associated with IBS and FD. Food allergy (OR=1.66; 95% CI=1.15-2.40, P=0.007), psoriasis (OR=1.81; 95% CI=1.19-2.74, P=0.006) and rheumatoid arthritis (OR=1.68; 95% CI=1.15-2.4, P=0.007) were independent risk factors for IBS, controlling for age, gender and psychological distress. In FD, asthma (OR=1.32; 95% CI=1.04-1.68, P=0.025) and food allergy (OR=1.78; 95% CI=1.28-2.49, P=0.001) were independent predictors, controlling for age, sex and psychological distress. There is evidence that both atopic and autoimmune diseases are risk factors for FGIDs, independent of psychological distress, differing in IBS and FD. This provides evidence that different peripheral pathways may be involved in the pathogenesis of certain FGIDs.

Although it has been reported that adult lactose malabsorption (ALM) is relatively common among Arabs, data on the prevalence of ALM in the Saudi and Yemeni populations are scant. We have determine...

Objetivo: realizar uma revisão integrativa sobre a função dos prebióticos e probióticos na manutenção da saúde, bem como suas aplicações no tratamento da constipação idiopática crônica (CIC), da síndrome do intestino irritável (SII) e da doença inflamatória intestinal (DII). Metodologia: trata-se de uma revisão integrativa da literatura, cuja busca dos estudos foi realizada nas bases de dados Cochrane e PubMed, com análise de trabalhos publicados nos últimos dez anos (2010-2020) escritos em inglês. Resultados: O uso de probióticos na CIC e SII mostrou efeitos benéficos na redução dos sintomas dessas doenças, modificação na microbiota e melhora na qualidade de vida dos pacientes. Na CIC, a inulina foi o prebiótico com mais efeitos positivos na sintomatologia da doença. Na DII, o uso de prebióticos e probióticos mostrou efeitos benéficos discretamente maiores para a RCU do que para a DC. Conclusão: Prebióticos e probióticos podem trazer tanto benefícios preventivos quanto terapêuticos à saúde intestinal, com ações diretas e indiretas na microbiota, imunidade e processos metabólicos do hospedeiro. A utilização desses compostos e microrganismos nas doenças estudadas demonstram resultados promitentes, principalmente, no campo dos probióticos. A partir da análise dos ensaios clínicos, as cepas promissoras no tratamento da DII foram Bifidobacterium, Lactobacillus, Enterococcus faecium (DC e RCU) e Clostridium butyricum (RCU). No entanto, salientamos a necessidade de estudos mais homogêneos no tratamento da DC com probióticos e prebióticos e o uso de prebióticos na SII.

NIH Conferences15 June 2010National Institutes of Health Consensus Development Conference: Lactose Intolerance and HealthFREEFrederick J. Suchy, MD, Patsy M. Brannon, PhD, RD, Thomas O. Carpenter, MD, Jose R. Fernandez, PhD, Vicente Gilsanz, MD, PhD, Jeffrey B. Gould, MD, MPH, Karen Hall, MD, PhD, Siu L. Hui, PhD, Joanne Lupton, PhD, Julie Mennella, PhD, Natalie J. Miller, BS, Stavroula Kalis Osganian, MD, ScD, MPH, Deborah E. Sellmeyer, MD, and Marshall A. Wolf, MD*Frederick J. Suchy, MDFrom Mount Sinai School of Medicine of New York University, Mount Sinai Kravis Children's Hospital, New York, New York; Cornell University, Ithaca, New York; Yale Center for X-linked Hypophosphatemia, Yale School of Medicine, New Haven, Connecticut; The University of Alabama at Birmingham, Birmingham, Alabama; Children's Imaging Research Program, Children's Hospital Los Angeles, and Keck School of Medicine, University of Southern California, Los Angeles, California;Stanford University School of Medicine, Stanford, California; University of Michigan Medical School and Geriatric Research, Education, and Clinical Center, Veterans Affairs Ann Arbor Healthcare System, Ann Arbor, Michigan; Center for Aging Research, Indiana University School of Medicine and Regenstrief Institute, Indianapolis, Indiana; Texas A&M University, College Station, Texas;Monell Chemical Senses Center and School of Veterinary Medicine of the University of Pennsylvania, Philadelphia, Pennsylvania; Harvard University, Children's Hospital Boston, Harvard Medical School, and Brigham and Women's Hospital, Boston, Massachusetts; and Metabolic Bone Center, Johns Hopkins Bayview Medical Center, Baltimore, Maryland., Patsy M. Brannon, PhD, RDFrom Mount Sinai School of Medicine of New York University, Mount Sinai Kravis Children's Hospital, New York, New York; Cornell University, Ithaca, New York; Yale Center for X-linked Hypophosphatemia, Yale School of Medicine, New Haven, Connecticut; The University of Alabama at Birmingham, Birmingham, Alabama; Children's Imaging Research Program, Children's Hospital Los Angeles, and Keck School of Medicine, University of Southern California, Los Angeles, California;Stanford University School of Medicine, Stanford, California; University of Michigan Medical School and Geriatric Research, Education, and Clinical Center, Veterans Affairs Ann Arbor Healthcare System, Ann Arbor, Michigan; Center for Aging Research, Indiana University School of Medicine and Regenstrief Institute, Indianapolis, Indiana; Texas A&M University, College Station, Texas;Monell Chemical Senses Center and School of Veterinary Medicine of the University of Pennsylvania, Philadelphia, Pennsylvania; Harvard University, Children's Hospital Boston, Harvard Medical School, and Brigham and Women's Hospital, Boston, Massachusetts; and Metabolic Bone Center, Johns Hopkins Bayview Medical Center, Baltimore, Maryland., Thomas O. Carpenter, MDFrom Mount Sinai School of Medicine of New York University, Mount Sinai Kravis Children's Hospital, New York, New York; Cornell University, Ithaca, New York; Yale Center for X-linked Hypophosphatemia, Yale School of Medicine, New Haven, Connecticut; The University of Alabama at Birmingham, Birmingham, Alabama; Children's Imaging Research Program, Children's Hospital Los Angeles, and Keck School of Medicine, University of Southern California, Los Angeles, California;Stanford University School of Medicine, Stanford, California; University of Michigan Medical School and Geriatric Research, Education, and Clinical Center, Veterans Affairs Ann Arbor Healthcare System, Ann Arbor, Michigan; Center for Aging Research, Indiana University School of Medicine and Regenstrief Institute, Indianapolis, Indiana; Texas A&M University, College Station, Texas;Monell Chemical Senses Center and School of Veterinary Medicine of the University of Pennsylvania, Philadelphia, Pennsylvania; Harvard University, Children's Hospital Boston, Harvard Medical School, and Brigham and Women's Hospital, Boston, Massachusetts; and Metabolic Bone Center, Johns Hopkins Bayview Medical Center, Baltimore, Maryland., Jose R. Fernandez, PhDFrom Mount Sinai School of Medicine of New York University, Mount Sinai Kravis Children's Hospital, New York, New York; Cornell University, Ithaca, New York; Yale Center for X-linked Hypophosphatemia, Yale School of Medicine, New Haven, Connecticut; The University of Alabama at Birmingham, Birmingham, Alabama; Children's Imaging Research Program, Children's Hospital Los Angeles, and Keck School of Medicine, University of Southern California, Los Angeles, California;Stanford University School of Medicine, Stanford, California; University of Michigan Medical School and Geriatric Research, Education, and Clinical Center, Veterans Affairs Ann Arbor Healthcare System, Ann Arbor, Michigan; Center for Aging Research, Indiana University School of Medicine and Regenstrief Institute, Indianapolis, Indiana; Texas A&M University, College Station, Texas;Monell Chemical Senses Center and School of Veterinary Medicine of the University of Pennsylvania, Philadelphia, Pennsylvania; Harvard University, Children's Hospital Boston, Harvard Medical School, and Brigham and Women's Hospital, Boston, Massachusetts; and Metabolic Bone Center, Johns Hopkins Bayview Medical Center, Baltimore, Maryland., Vicente Gilsanz, MD, PhDFrom Mount Sinai School of Medicine of New York University, Mount Sinai Kravis Children's Hospital, New York, New York; Cornell University, Ithaca, New York; Yale Center for X-linked Hypophosphatemia, Yale School of Medicine, New Haven, Connecticut; The University of Alabama at Birmingham, Birmingham, Alabama; Children's Imaging Research Program, Children's Hospital Los Angeles, and Keck School of Medicine, University of Southern California, Los Angeles, California;Stanford University School of Medicine, Stanford, California; University of Michigan Medical School and Geriatric Research, Education, and Clinical Center, Veterans Affairs Ann Arbor Healthcare System, Ann Arbor, Michigan; Center for Aging Research, Indiana University School of Medicine and Regenstrief Institute, Indianapolis, Indiana; Texas A&M University, College Station, Texas;Monell Chemical Senses Center and School of Veterinary Medicine of the University of Pennsylvania, Philadelphia, Pennsylvania; Harvard University, Children's Hospital Boston, Harvard Medical School, and Brigham and Women's Hospital, Boston, Massachusetts; and Metabolic Bone Center, Johns Hopkins Bayview Medical Center, Baltimore, Maryland., Jeffrey B. Gould, MD, MPHFrom Mount Sinai School of Medicine of New York University, Mount Sinai Kravis Children's Hospital, New York, New York; Cornell University, Ithaca, New York; Yale Center for X-linked Hypophosphatemia, Yale School of Medicine, New Haven, Connecticut; The University of Alabama at Birmingham, Birmingham, Alabama; Children's Imaging Research Program, Children's Hospital Los Angeles, and Keck School of Medicine, University of Southern California, Los Angeles, California;Stanford University School of Medicine, Stanford, California; University of Michigan Medical School and Geriatric Research, Education, and Clinical Center, Veterans Affairs Ann Arbor Healthcare System, Ann Arbor, Michigan; Center for Aging Research, Indiana University School of Medicine and Regenstrief Institute, Indianapolis, Indiana; Texas A&M University, College Station, Texas;Monell Chemical Senses Center and School of Veterinary Medicine of the University of Pennsylvania, Philadelphia, Pennsylvania; Harvard University, Children's Hospital Boston, Harvard Medical School, and Brigham and Women's Hospital, Boston, Massachusetts; and Metabolic Bone Center, Johns Hopkins Bayview Medical Center, Baltimore, Maryland., Karen Hall, MD, PhDFrom Mount Sinai School of Medicine of New York University, Mount Sinai Kravis Children's Hospital, New York, New York; Cornell University, Ithaca, New York; Yale Center for X-linked Hypophosphatemia, Yale School of Medicine, New Haven, Connecticut; The University of Alabama at Birmingham, Birmingham, Alabama; Children's Imaging Research Program, Children's Hospital Los Angeles, and Keck School of Medicine, University of Southern California, Los Angeles, California;Stanford University School of Medicine, Stanford, California; University of Michigan Medical School and Geriatric Research, Education, and Clinical Center, Veterans Affairs Ann Arbor Healthcare System, Ann Arbor, Michigan; Center for Aging Research, Indiana University School of Medicine and Regenstrief Institute, Indianapolis, Indiana; Texas A&M University, College Station, Texas;Monell Chemical Senses Center and School of Veterinary Medicine of the University of Pennsylvania, Philadelphia, Pennsylvania; Harvard University, Children's Hospital Boston, Harvard Medical School, and Brigham and Women's Hospital, Boston, Massachusetts; and Metabolic Bone Center, Johns Hopkins Bayview Medical Center, Baltimore, Maryland., Siu L. Hui, PhDFrom Mount Sinai School of Medicine of New York University, Mount Sinai Kravis Children's Hospital, New York, New York; Cornell University, Ithaca, New York; Yale Center for X-linked Hypophosphatemia, Yale School of Medicine, New Haven, Connecticut; The University of Alabama at Birmingham, Birmingham, Alabama; Children's Imaging Research Program, Children's Hospital Los Angeles, and Keck School of Medicine, University of Southern California, Los Angeles, California;Stanford University School of Medicine, Stanford, California; University of Michigan Medical School and Geriatric Research, Education, and Clinical Center, Veterans Affairs Ann Arbor Healthcare System, Ann Arbor, Michigan; Center for Aging Research, Indiana University School of Medicine and Regenstrief Institute, Indianapolis, Indiana; Texas A&M University, College Station, Texas;Monell Chemical Senses Center and School of Veterinary Medicine of the University of Pennsylvania, Philadelphia, Pennsylvania; Harvard University, Children's Hospital Boston, Harvard Medical School, and Brigham and Women's Hospital, Boston, Massachusetts; and Metabolic Bone Center, Johns Hopkins Bayview Medical Center, Baltimore, Maryland., Joanne Lupton, PhDFrom Mount Sinai School of Medicine of New York University, Mount Sinai Kravis Children's Hospital, New York, New York; Cornell University, Ithaca, New York; Yale Center for X-linked Hypophosphatemia, Yale School of Medicine, New Haven, Connecticut; The University of Alabama at Birmingham, Birmingham, Alabama; Children's Imaging Research Program, Children's Hospital Los Angeles, and Keck School of Medicine, University of Southern California, Los Angeles, California;Stanford University School of Medicine, Stanford, California; University of Michigan Medical School and Geriatric Research, Education, and Clinical Center, Veterans Affairs Ann Arbor Healthcare System, Ann Arbor, Michigan; Center for Aging Research, Indiana University School of Medicine and Regenstrief Institute, Indianapolis, Indiana; Texas A&M University, College Station, Texas;Monell Chemical Senses Center and School of Veterinary Medicine of the University of Pennsylvania, Philadelphia, Pennsylvania; Harvard University, Children's Hospital Boston, Harvard Medical School, and Brigham and Women's Hospital, Boston, Massachusetts; and Metabolic Bone Center, Johns Hopkins Bayview Medical Center, Baltimore, Maryland., Julie Mennella, PhDFrom Mount Sinai School of Medicine of New York University, Mount Sinai Kravis Children's Hospital, New York, New York; Cornell University, Ithaca, New York; Yale Center for X-linked Hypophosphatemia, Yale School of Medicine, New Haven, Connecticut; The University of Alabama at Birmingham, Birmingham, Alabama; Children's Imaging Research Program, Children's Hospital Los Angeles, and Keck School of Medicine, University of Southern California, Los Angeles, California;Stanford University School of Medicine, Stanford, California; University of Michigan Medical School and Geriatric Research, Education, and Clinical Center, Veterans Affairs Ann Arbor Healthcare System, Ann Arbor, Michigan; Center for Aging Research, Indiana University School of Medicine and Regenstrief Institute, Indianapolis, Indiana; Texas A&M University, College Station, Texas;Monell Chemical Senses Center and School of Veterinary Medicine of the University of Pennsylvania, Philadelphia, Pennsylvania; Harvard University, Children's Hospital Boston, Harvard Medical School, and Brigham and Women's Hospital, Boston, Massachusetts; and Metabolic Bone Center, Johns Hopkins Bayview Medical Center, Baltimore, Maryland., Natalie J. Miller, BSFrom Mount Sinai School of Medicine of New York University, Mount Sinai Kravis Children's Hospital, New York, New York; Cornell University, Ithaca, New York; Yale Center for X-linked Hypophosphatemia, Yale School of Medicine, New Haven, Connecticut; The University of Alabama at Birmingham, Birmingham, Alabama; Children's Imaging Research Program, Children's Hospital Los Angeles, and Keck School of Medicine, University of Southern California, Los Angeles, California;Stanford University School of Medicine, Stanford, California; University of Michigan Medical School and Geriatric Research, Education, and Clinical Center, Veterans Affairs Ann Arbor Healthcare System, Ann Arbor, Michigan; Center for Aging Research, Indiana University School of Medicine and Regenstrief Institute, Indianapolis, Indiana; Texas A&M University, College Station, Texas;Monell Chemical Senses Center and School of Veterinary Medicine of the University of Pennsylvania, Philadelphia, Pennsylvania; Harvard University, Children's Hospital Boston, Harvard Medical School, and Brigham and Women's Hospital, Boston, Massachusetts; and Metabolic Bone Center, Johns Hopkins Bayview Medical Center, Baltimore, Maryland., Stavroula Kalis Osganian, MD, ScD, MPHFrom Mount Sinai School of Medicine of New York University, Mount Sinai Kravis Children's Hospital, New York, New York; Cornell University, Ithaca, New York; Yale Center for X-linked Hypophosphatemia, Yale School of Medicine, New Haven, Connecticut; The University of Alabama at Birmingham, Birmingham, Alabama; Children's Imaging Research Program, Children's Hospital Los Angeles, and Keck School of Medicine, University of Southern California, Los Angeles, California;Stanford University School of Medicine, Stanford, California; University of Michigan Medical School and Geriatric Research, Education, and Clinical Center, Veterans Affairs Ann Arbor Healthcare System, Ann Arbor, Michigan; Center for Aging Research, Indiana University School of Medicine and Regenstrief Institute, Indianapolis, Indiana; Texas A&M University, College Station, Texas;Monell Chemical Senses Center and School of Veterinary Medicine of the University of Pennsylvania, Philadelphia, Pennsylvania; Harvard University, Children's Hospital Boston, Harvard Medical School, and Brigham and Women's Hospital, Boston, Massachusetts; and Metabolic Bone Center, Johns Hopkins Bayview Medical Center, Baltimore, Maryland., Deborah E. Sellmeyer, MDFrom Mount Sinai School of Medicine of New York University, Mount Sinai Kravis Children's Hospital, New York, New York; Cornell University, Ithaca, New York; Yale Center for X-linked Hypophosphatemia, Yale School of Medicine, New Haven, Connecticut; The University of Alabama at Birmingham, Birmingham, Alabama; Children's Imaging Research Program, Children's Hospital Los Angeles, and Keck School of Medicine, University of Southern California, Los Angeles, California;Stanford University School of Medicine, Stanford, California; University of Michigan Medical School and Geriatric Research, Education, and Clinical Center, Veterans Affairs Ann Arbor Healthcare System, Ann Arbor, Michigan; Center for Aging Research, Indiana University School of Medicine and Regenstrief Institute, Indianapolis, Indiana; Texas A&M University, College Station, Texas;Monell Chemical Senses Center and School of Veterinary Medicine of the University of Pennsylvania, Philadelphia, Pennsylvania; Harvard University, Children's Hospital Boston, Harvard Medical School, and Brigham and Women's Hospital, Boston, Massachusetts; and Metabolic Bone Center, Johns Hopkins Bayview Medical Center, Baltimore, Maryland., and Marshall A. Wolf, MD*From Mount Sinai School of Medicine of New York University, Mount Sinai Kravis Children's Hospital, New York, New York; Cornell University, Ithaca, New York; Yale Center for X-linked Hypophosphatemia, Yale School of Medicine, New Haven, Connecticut; The University of Alabama at Birmingham, Birmingham, Alabama; Children's Imaging Research Program, Children's Hospital Los Angeles, and Keck School of Medicine, University of Southern California, Los Angeles, California;Stanford University School of Medicine, Stanford, California; University of Michigan Medical School and Geriatric Research, Education, and Clinical Center, Veterans Affairs Ann Arbor Healthcare System, Ann Arbor, Michigan; Center for Aging Research, Indiana University School of Medicine and Regenstrief Institute, Indianapolis, Indiana; Texas A&M University, College Station, Texas;Monell Chemical Senses Center and School of Veterinary Medicine of the University of Pennsylvania, Philadelphia, Pennsylvania; Harvard University, Children's Hospital Boston, Harvard Medical School, and Brigham and Women's Hospital, Boston, Massachusetts; and Metabolic Bone Center, Johns Hopkins Bayview Medical Center, Baltimore, Maryland.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-152-12-201006150-00248 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail National Institutes of Health (NIH) consensus and state-of-the-science statements are prepared by independent panels of health professionals and public representatives on the basis of 1) the results of a systematic literature review prepared under contract with the Agency for Healthcare Research and Quality; 2) presentations by investigators working in areas relevant to the conference questions during a 2-day public session; 3) questions and statements from conference attendees during open discussion periods that are part of the public session; and 4) closed deliberations by the panel during the remainder of the second day and morning of the third. This statement is an independent report of the panel and is not a policy statement of the National Institutes of Health or the U.S. government. The following statement is an abridged version of the panel's report, which is available in full atconsensus.nih.gov/2010/lactosestatement.htm.Lactose intolerance is the syndrome of diarrhea, abdominal pain, flatulence, or bloating occurring after lactose ingestion. These symptoms, which are produced by malabsorption of lactose, a sugar found in milk and other dairy products, often cause afflicted individuals to avoid dairy products in their diets. Lactose malabsorption is caused by a decreased ability to digest lactose that is due to a deficiency in the levels of the enzyme lactase. Lactase breaks lactose down into 2 simpler sugars, glucose and galactose, which are readily absorbed into the bloodstream. This enzyme is produced by expression of the lactase–phlorizin hydrolase gene in the cells lining the small intestine.All infants produce lactase and successfully digest lactose provided by human milk or by infant formulas. However, sometime after weaning, a genetically programmed decrease in lactase (lactase nonpersistence) occurs in most children worldwide.The symptoms of lactose intolerance result from bacterial fermentation of undigested lactose in the colon. Lactose malabsorption can be diagnosed by having individuals ingest a standard dose of lactose after fasting and measuring breath hydrogen; elevated breath hydrogen levels are caused by bacterial fermentation of undigested lactose in the colon. Other diagnostic tools include measuring lactase activity in an intestinal biopsy sample or genetic testing for the common polymorphism that is linked to lactase nonpersistence. The demonstration of lactose malabsorption does not necessarily indicate that an individual will have symptoms. Many variables determine whether a person who malabsorbs lactose develops symptoms, including the dose of lactose ingested, the residual intestinal lactase activity, the ingestion of food along with lactose, the ability of the colonic flora to ferment lactose, and individual sensitivity to the products of lactose fermentation.Current management often relies on reducing lactose exposure by avoiding milk and milk-containing products or by drinking milk in which the lactose has been prehydrolyzed with lactase. Alternatively, persons with lactase nonpersistence may tolerate moderate amounts of dairy products ingested with other foods. Many individuals, however, mistakenly ascribe symptoms of diverse intestinal disorders to lactose intolerance without undergoing testing. This misconception becomes intergenerational, when parents with self-diagnosed lactose intolerance place their children on lactose-restricted diets (even in the absence of symptoms) in the mistaken belief that the children will develop symptoms if given lactose.The public health burden from deficiencies attributable to lactose intolerance has not been established. Many adults and children who avoid dairy products—which constitute a readily accessible source of calcium, vitamin D, and other nutrients—are not ingesting adequate amounts of these essential nutrients. For example, most African-American adolescents consume inadequate amounts of calcium and vitamin D because they avoid dairy products. Deficient intakes of calcium and vitamin D are risk factors for decreased bone mineral density. This may increase the risk for fracture throughout the life cycle, especially in postmenopausal women. Very low intake of vitamin D can lead to the development of rickets, especially in children of African descent and other highly pigmented persons. Although reduced-lactose dairy and nondairy alternative products are typically fortified with calcium, vitamin D, and other nutrients, they may be more expensive and less widely available than conventional dairy products. The bioequivalence of these and other calcium supplements is uncertain.To examine this important topic more closely, the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the Office of Medical Applications of Research of the National Institutes of Health convened a Consensus Development Conference. This conference, which addressed several questions, was informed by a systematic review conducted by the Minnesota Evidence-based Practice Center.Question 1What is the prevalence of lactose intolerance, and how does this prevalence differ by race, ethnicity, and age?The prevalence of lactose intolerance in the United States cannot be estimated from available data. The potentially relevant studies identified in the systematic review used the definition of lactose malabsorption rather than an accurate and appropriate definition of lactose intolerance and did not evaluate a representative sample of the U.S. population. Studies that assessed self-reported lactose intolerance provided limited insight because the self-diagnoses were not confirmed by testing for lactose malabsorption, and the symptoms seen in true lactose intolerance may result from several other conditions, including the irritable bowel syndrome. Some studies evaluated only the genetic predisposition to lower-than-expected lactase levels in adults (lactase nonpersistence) without assessing lactose malabsorption or intolerance directly.Despite the limitations of available studies, several noteworthy observations emerged. First, lactose intolerance determined by self-report or nonblinded lactose challenge is less frequent across all ethnic groups than is lactose malabsorption determined by breath hydrogen tests or lactase nonpersistence determined by biopsy or genetic testing. Second, lactose intolerance, lactose malabsorption, and lactase nonpersistence vary across racial and ethnic groups, with the lowest reported occurrence in European Americans and higher (although variable) occurrence in African Americans, Hispanic Americans, Asian Americans, and Native Americans. Finally, lactose intolerance with nonblinded lactose challenge and lactose malabsorption was low in young children but increased with age. In children younger than 6 years, lactose malabsorption was low in all the studies and peaked between 10 and 16 years of age. Little evidence suggests that lactose intolerance increases in older persons. These trends need to be verified by representative population studies by using the case definition of lactose intolerance.Question 2What are the health outcomes of dairy-exclusion diets?The health outcomes of dairy-exclusion diets depend on whether other sources of nutrients, such as calcium and vitamin D, occur in the diet in sufficient quantities to replace dairy products as a source of these nutrients, and to what extent other components of milk are beneficial.Calcium is necessary for normal growth and bone development, as well as subsequent maintenance of bone density. The strongest argument for promotion of dairy ingestion is the beneficial effect of calcium (and fortified vitamin D in milk) on growth and development of the skeleton. Calcium is necessary for adequate bone accretion and optimal peak bone mass, which is a major determinant of risk for osteoporosis and fragility fractures later in adult life. Evidence suggests that certain age groups, such as children and teenagers, may be at increased risk for deficient bone acquisition if their diets are deficient in calcium or vitamin D. Weak evidence indicates that children with calcium-deficient diets have increased fracture rates. The maximal accumulation of bone mineral, and therefore the maximal calcium requirement, occurs during puberty. Although studies indicate that young children who drink milk are likely to meet or exceed the adequate intake for calcium, teenagers as a group tend not to take in enough calcium to meet recommended needs. This problem is exacerbated by dairy avoidance in individuals who consider themselves lactose intolerant, regardless of whether they have undergone objective testing for lactose intolerance.Studies show that the presence of lactose does not necessarily affect the efficiency of calcium absorption across the intestine and that persons with lactase nonpersistence do not have substantial impairment in calcium absorption. Thus, the limiting factor in achieving optimal peak bone mass in young individuals is the intake of calcium. Similarly, in older individuals, low calcium intake rather than deficient absorption is probably a major factor contributing to loss of bone mass. Replacement of calcium using supplements or dairy products slows the rate of bone loss in older people, possibly as a result of an overall decrease in bone turnover. Across the age spectrum, the factor that limits adequate calcium accrual in many individuals probably is dairy avoidance.Dairy-exclusion diets may decrease gastrointestinal symptoms (bloating, cramps, flatus, and diarrhea) in symptomatic persons who have lactose malabsorption or intolerance. The degree of relief is probably related to the degree of expression of lactase and the quantity of lactose ingested. People who remain symptomatic on a dairy-exclusion diet may have other causes for their gastrointestinal symptoms, such as the irritable bowel syndrome, celiac disease, inflammatory bowel disease, or small-bowel bacterial overgrowth.Question 3What amount of daily lactose intake is tolerable in persons with diagnosed lactose intolerance?Among persons with appropriately diagnosed lactose intolerance, differences in several factors—including lactase activity, gastric emptying rates, fecal bacterial metabolites, colonic mucosal absorptive capacity, and intestinal transit time—can greatly influence their susceptibility to development of intolerance symptoms after ingestion of foods and beverages containing lactose. Individuals differ in the intensity of symptoms of lactose intolerance because of differences in abdominal pain perception and the psychological effect of pain and social discomfort. Determining the amount of lactose that can be tolerated is necessary to develop evidence-based dietary recommendations that meet the needs of the individual.High-quality evidence that addresses the above question is limited. Pertinent studies used different definitions of lactose intolerance, sample selection criteria, lactose administration procedures, and assessment and follow-up methods. Most studies used a single dose of lactose administered without food and evaluated short-term responses. Efforts often were not made to mask the taste difference between lactose-free milk and milk containing lactose. Only a handful of studies tested the participants in a double-blinded manner with increasing amounts of lactose administered throughout the day to determine the daily tolerable lactose dose. Most studies examined small numbers of participants, and few or no studies focused exclusively on children, pregnant women, or lactating women.In most studies, participants were classified as malabsorbers or absorbers on the basis of breath hydrogen measurement or a blood glucose test, and symptoms of lactose intolerance were not always required for study entry. A blinded control was rarely used to define lactose intolerance at study entry; thus, it is probable that some individuals would have reported symptoms after ingestion of lactose-free solutions. Most studies investigated individuals with proven lactose ma

A Gastroenterologist's Guide to Probiotics

Symptoms of irritable bowel syndrome (IBS) and lactose intolerance (LI) overlap. Data on the frequency of LI in patients with IBS from India are scanty. The aim of this study was to evaluate: (i) the frequency of LI in patients with IBS and its various subtypes as compared with healthy subjects (HS) from northern India; (ii) the relationship between self-reported milk intolerance and laboratory evidence of LI; and (iii) the role of small intestinal bacterial overgrowth in LI in patients with IBS. 124 patients with IBS (Rome II criteria) and 53 age- and gender-matched HS were studied for LI using the lactose hydrogen breath test (LHBT) and the lactose tolerance test (LTT). Symptoms following lactose ingestion (diarrhea, bloating or distension) during the test and history of milk intolerance were recorded. Sixty-nine of the patients with IBS also underwent a glucose hydrogen breath test (GHBT). Patients with IBS were classified into those with diarrhea (IBS-D; >3 loose stools/d), constipation predominant (IBS-C; <3 stools/week) and indeterminate (IBS-I; between >or=3/week and <or= 3/d). 89/124 (72%) and 32/53 (60%, P = ns) IBS patients and HS were positive by LHBT and 82/124 (66%) and 38/53 (71%, P = ns) by LTT. Lactose intolerance as diagnosed either by LHBT or LTT was comparable among IBS patients and HS (102/124, 82% vs 41/53, 77%; P = ns). Peak breath hydrogen values during LHBT were also comparable among patients with IBS and HS (64 +/- 40 p.p.m. vs 61 +/- 44 p.p.m.). Patients with IBS developed symptoms following lactose ingestion more frequently than HS (68/124 vs 18/53, P = 0.01). Glucose hydrogen breath test was positive in 9/69 (13%) patients with IBS and was comparable among patients with (8/57, 14%) and without LI (1/12, 8%). Thirty had IBS-D whereas 94 had other subtypes of IBS (IBS-C, n = 9 and IBS-I, n = 85). The frequency of LI in IBS-D was similar to that of other subtypes (26/30, 86% vs 76/94, 80%; P = ns). The positive and negative predictive value of self-reported milk intolerance in detecting LI was 81% and 23%, respectively. The frequency of LI is high and comparable among IBS patients and HS from northern India. Patients with IBS more often reported symptoms following lactose ingestion despite levels of breath hydrogen being similar to HS. The frequency of LI in patients with IBS-D was comparable to that in patients with other types of IBS. Self-reported milk intolerance has poor sensitivity in detecting LI.

Food, the Immune System, and the Gastrointestinal Tract

The importance of lactose malabsorption in irritable bowel syndrome (IBS) is not well defined and these patients often complain of lactose intolerance. To objectively measure lactose malabsorption, a hydrogen breath test (HBT) can be performed, but a discrepancy emerges between the results of the HBT and the symptomatic response during the HBT. To determine in a group of IBS patients whether self-perceived lactose intolerance and the symptomatic response to lactose HBT were conditioned by other factors besides the presence of lactose malabsorption. Oral challenge to lactose (50 g) was tested in 51 IBS patients to assess HBT malabsorption and the symptomatic response to lactose intolerance was scored on a validated questionnaire. Allergological screening for common inhalants and food allergens (including cow's milk) was performed. The presence of psychological factors (e.g. anxiety, depression, fatigue) was evaluated using validated questionnaires. A total of 21 out of 51 patients (41.1%) were self-perceived to be lactose intolerant, 24/51 (47%) had a positive HBT, and 14/51 (27.4%) presented with symptoms of lactose intolerance during HBT. The serological screening for inhalant and food allergens was positive in 6/21 (28.6%) and 4/21 (19%) of patients who self-perceived lactose intolerance and in 5/14 (37.5%) and 3/14 (21.4%) in intolerant patients symptomatic during HBT. Only 1/51 (1.9%) presented evidence of IgE-mediated hypersensitivity to cow's milk. Patients who experienced symptoms of lactose intolerance during HBT presented more severe IBS symptoms [326 (296-398) vs. 215 (126-295) P=0.05] and a higher score of anxiety, depression, and fatigue. Factors influencing the symptoms of lactose intolerance during HBT resulted in an increase in hydrogen produced and in the severity of IBS. In a cohort of 51 IBS patients, the symptoms of lactose intolerance during HBT were influenced by the capacity to absorb lactose and the severity of IBS. Other factors, such as the psychological status or an adverse reaction to milk, merit consideration as potential cofactors involved in lactose perception and tolerance.

Nowadays irritable bowel syndrome (IBS) and lactose intolerance (LI) are two very frequent diseases. IBS is a functional disorder, while LI is caused by the inability to digest lactose. LI is often incorrectly diagnosed as IBS. The aim of our study is to identify LI patients among IBS patients, so as to set up a correct therapy. We enrolled 259 patients with IBS and we compared them to a control group of 108 patients. All patients underwent H<inf>2</inf> Breath-Test (HBT) and two questionnaires regarding the symptoms associated with IBS and LI were administered to the intolerant subjects and one questionnaire to IBS patients with no LI. At the HBT, 79.9% (N.=207) of patients with IBS were positive, while in the control group were positive 25.0% (N.=27) of subjects (P<0.001). The questionnaires showed, after a month of therapy, a marked improvement in LI symptoms subjects. In addition, there was also a prevalence of more severe symptoms among subjects with IBS and LI than those with IBS and no LI. We can affirm that most patients with initial diagnosis of IBS are, instead, lactose intolerant. This diagnosis allows us to undertake an adequate therapy so as to improve symptoms and quality of life. Therefore it is important to include LI in the pathologies with which IBS enters into differential diagnosis.

The gut microbiota (GM) is a complex and dynamic community of microorganisms that colonize the human gastrointestinal tract and play an important role in various aspects of the host’s physiology and health. GM is involved in digestion and assimilation of nutrients, synthesis of vitamins and metabolites, modulation of the immune system and defense against pathogens. However, the gut microbiota can also be a source of inflammation and disease when its composition and function are altered. This phenomenon, known as dysbiosis, is associated with almost all gastrointestinal diseases and is most prominent in inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), colorectal cancer, and celiac disease. Considering the important role of GM in the pathogenesis of IBD and other diseases of the gastrointestinal tract, several methods of its modification have been proposed, including the use of probiotics, prebiotics, synbiotics, antibiotics, dietary interventions, fecal microbiota transplantation (FTM) and bacteriophage therapy. However, drawing general conclusions about the efficacy and safety of these approaches is often difficult due to variability in interventions, doses, timing of administration, and the inevitable heterogeneity of host microbiome profiles and gut status. This review presents the results of a large international survey, purposed on the assessment of current practice, preferences, challenges, and expectations of doctors regarding the assessment of the composition of GM and the use of antibiotics, probiotics and TFM in intestinal diseases. The survey was also aimed on the identification of factors influencing the decision‑making process by doctors and barriers limiting the implementation of GM modification in clinical practice. Conclusions drawn from the results of the survey highlight the need for further research, standardization of techniques and evidence‑based recommendations to optimize the use of probiotics, antibiotics and TFM in clinical practice.