Lactose Malabsorption and Presumed Related Disorders: A Review of Current Evidence.

BACKGROUND: Lactose malabsorption (LM) is a frequent clinical problem associated with several digestive and extra-digestive diseases. The aim of this manuscript was to clarify the real clinical impact of LM on these disorders. METHODS: A literature search for digestive and extra-digestive disorders related to LM was carried out using PubMed, Medline and Cochrane. RESULTS: A transient lactase deficiency is present in celiac disease (CD) on a normal diet. The persistence of symptoms in CD on a gluten-free diet may be instead, in part, attributed to a primary LM. Similar circumstances are present in inflammatory bowel diseases (IBD), in which LM can be responsible for a part of persistent symptoms in IBD on clinical remission. LM and irritable bowel syndrome (IBS) are instead independent conditions. On the other hand, a lactose-restricted diet may be useful for some IBS patients. A reduced lactose intake can lead to low bone mass and limited risk of fragility fractures. Finally, the absorption of levothyroxine could be conditioned by LM. CONCLUSIONS: LM can be responsible for persistent symptoms in CD and IBD. The association with IBS seems to be casual. Bone mass and levothyroxine absorption can be affected by LM.

Effects of Prokinetics on the Digestive Tract.

BACKGROUND: Functional gastrointestinal disorders account for at least a third of visits to gastroenterology clinics. Despite pathophysiological complexity, impaired gut motility may be frequently present in these disorders. INTRODUCTION: Prokinetics are a class of drugs that promote gastrointestinal motility, accelerate transit, and potentially improve digestive symptoms. Several prokinetic agents with a great variety of mechanisms of action are available. AIM: The purpose of this paper is to update our current knowledge about the efficacy and safety of prokinetics. METHODS: A literature search on efficacy and safety of prokinetics was carried out using the online databases of Pubmed, Medline, and Cochrane. RESULTS: Based on the action of different receptors, prokinetics mainly comprise dopamine antagonists, 5HT4 agonists, motilin agonists, ghrelin agonists, and cholinergic agonists. Prokinetics have the potential to improve motility function in all segments of the digestive tract, from the esophagus to the colon. In particular, drug international agencies have approved antidopaminergic metoclopramide for the treatment of gastroparesis and serotoninergic prucalopride for chronic constipation not responsive to traditional laxatives. Arrhythmias by QT prolongation and galactorrhea by prolactin stimulation are the more frequent side effects related to prokinetics use. CONCLUSION: Old and new prokinetics are effective in ameliorating digestive motility disorders and related symptoms and are widely prescribed. Special attention should be paid to the potential adverse events of these agents.

Hydrogen Breath Tests: Are They Really Useful in the Nutritional Management of Digestive Disease?

BACKGROUND: Carbohydrate malabsorption is a frequent digestive problem associated with abdominal pain, bloating and diarrhea. Hydrogen breath testing (BT) represents the most reliable and validated diagnostic technique. The aim of this manuscript was to clarify the usefulness of BTs in the nutritional management of these disorders. METHODS: A literature search for BT related to carbohydrate malabsorption was carried out using the online databases of Pubmed, Medline and Cochrane. RESULTS: Lactose BT showed good sensitivity and optimal specificity for lactose malabsorption. However, an accurate diagnosis of lactose intolerance should require blind lactose challenge although this method is difficult to utilize in clinical practice. Regarding dose-depending fructose and sorbitol malabsorption, BTs could not add diagnostic advantage compared with a direct dietary intervention. In addition, carbohydrates are fundamental components of fermentable oligo-, di- and monosaccharides and polyols (FODMAPs). Before starting a low FODMAP diet, lactose BT should be suggested in a population with low prevalence of hypolactasia. CONCLUSIONS: BTs represent a valid and noninvasive technique in many digestive conditions. Regarding the management of carbohydrate intolerance, lactose BT can be recommended with some limitations. No sufficient evidence is available about the usefulness of BTs for other sugars in clinical practice.

Irritable Bowel Syndrome and Gluten-Related Disorders.

Background: Irritable bowel syndrome (IBS) is frequently associated with celiac disease (CD) and nonceliac gluten/wheat sensitivity (NCGS/NCWS), but epidemiological and pathophysiological aspects are still unclear. Furthermore, a gluten-free diet (GFD) can positively influence IBS symptoms. Methods: A comprehensive online search for IBS related to CD, NCGS and GFD was made using the Pubmed, Medline and Cochrane databases. Results: Although a systematic screening for CD in IBS is not recommended, CD prevalence can be increased in diarrhea-predominant IBS patients. On the other hand, IBS symptoms can be persistent in treated CD patients, and their prevalence tends to decrease on a GFD. IBS symptoms may overlap and be similar to those associated to nonceliac gluten and/or wheat sensitivity. Increased gut permeability could explain the gluten/wheat effects in IBS patients. Finally, a GFD could improve symptoms in a subgroup of IBS patients. Conclusions: The possible interplay between IBS and gluten-related disorders represents a scientifically and clinically challenging issue. Further studies are needed to confirm these data and better clarify the involved pathophysiological mechanisms.

Motility Disorders in Celiac Disease and Non-Celiac Gluten Sensitivity: The Impact of a Gluten-Free Diet.

Background: There is evidence that digestive motor disorders are frequently present in untreated celiac disease (CD) patients. Similarly, non-celiac gluten sensitivity (NCGS) can be associated with gut motor disorders. In both cases, gut dysmotility can improve or be completely reversed with a gluten-free diet (GFD). Methods: A literature search for motility disorders in CD and NCGS patients was carried out using the online databases PubMed, Medline and Cochrane. Results: Esophageal, gastric, small bowel and gallbladder motor disorders are common in both children and adults with CD. Although the clinical consequences of these disorders are not clearly defined, gastric dysfunction could affect drug absorption and metabolism in the thyroid and neurological conditions associated with CD. The impact of a GFD on motility disorders is, however, controversial. No systematic studies are available on NCGS. NCGS frequently overlaps with irritable bowel syndrome (IBS) and similar pathophysiological mechanisms may be hypothesized. Conclusions: Mucosal damage may affect gut motility in untreated CD through perturbation of hormonal and neuro-immunomodulatory regulation. A persistent low-grade mucosal inflammation could explain the cases of persistent motor disorders despite a GFD. Further studies are needed to definitely assess the role of gut motor disorders in NCGS.

Therapeutic Approach for Irritable Bowel Syndrome: Old and New Strategies.

BACKGROUND: Irritable bowel syndrome (IBS) is the most frequently diagnosed functional gastrointestinal disorder. It is characterised by abdominal pain, bloating and changes in bowel habits that can have a serious impact on the patient's quality of life. Treatment strategies are based on the nature and severity of the symptoms, the degree of functional impairment of the bowel habits, and the presence of psychosocial disorders. The purpose of this review is to update our current knowledge of therapeutic approach of this disorder. METHOD: A literature search for IBS therapy was carried out using the online databases of Pubmed, Medline and Cochrane. RESULTS: An ideal treatment begins by explaining this condition and providing reassurance to the patients. There is limited evidence for the efficacy, and tolerability of the therapies currently available for the treatment of IBS. There is also a limited availability of pharmacological agents licensed specifically for the treatment of IBS subtypes, although new agents have been recently proposed to this goal. Furthermore, patients often associate their complaints with the ingestion of foods containing FODMAPs (fermentable oligo-di-monosaccharides, and polyols) and gluten derivates and a personalized diet can be proposed. However, more severe symptoms can be associated with greater levels of psychosocial problems and a psychological approach and antidepressant drugs can be needed. CONCLUSION: The treatment of IBS remains focused on treating the patient's predominant, or most troublesome, symptoms. New promising treatments have recently become available for the treatment of IBS but long term studies are still needed.

Overview of pathophysiological features of GERD.

Gastroesophageal reflux disease (GERD) is a very prevalent condition and has a high impact on the quality of life. Nevertheless, pathophysiology is complex and multi-factorial. Several mechanisms have been proposed: decreased salivation, decreased lower esophageal sphincter pressure resting tone, presence of hiatal hernia, increased number of transient lower esophageal sphincter relaxations, increased acid, and pepsin secretion, duodeno-gastro-esophageal reflux of bile acids and trypsin. Other factors contributing to the pathophysiology of GERD include poor esophageal clearance, delayed gastric emptying and impaired mucosal defensive factors. Esophageal mucosa integrity is impaired both in patients with erosive esophagitis also in regions macroscopically normal and in NERD patients. Patients with functional heartburn have instead a normal mucosal integrity. The mechanisms underlying extra-esophageal GERD are instead more controversial. Reflux symptoms could be caused by esophageal hypersensitivity as a result of visceral neural pathway dysfunction. Multiple mechanisms influence the perception of GERD symptoms, such as the acidity of the refluxate, its proximal extent, the presence of gas in the refluxate, duodeno-gastro-esophageal reflux, mucosal integrity, and peripheral and central sensitization. Furthermore several risk factors can influence the onset of GERD and its complications such as life style, obesity, genetics, pregnancy, and stress. In particular obesity is associated with complications related to longstanding reflux such as erosive esophagitis, Barrett's esophagus, and esophageal adenocarcinoma. Understanding the pathophysiology of gastro-esophageal reflux is important for future targets for therapy. Further research is necessary to improve the current knowledge of the contributing factors leading to GERD.

Delayed gastric emptying does not normalize after gluten withdrawal in adult celiac disease.

Objective Delayed gastric emptying has been frequently detected in patients with untreated celiac disease. According to several studies, gluten withdrawal showed to be effective in normalizing the gastric emptying rate. The aim of this study was to evaluate the gastric emptying rate of solids in patients with celiac disease before and after a gluten-free diet. Methods Twelve adult patients with celiac disease (age range 20-57 years) and 30 healthy controls (age range 30-54 years) underwent a (13)C-octanoic acid breath test to measure gastric emptying. Half emptying time (t1/2) and lag phase (tlag) were calculated. After at least 12 months of a gluten-free diet, celiac patients underwent a new (13)C-octanoic acid breath test. A symptom score was utilized to detect dyspeptic and malabsorption symptoms in all the patients. Results The gastric motility parameters, t1/2 and tlag, were significantly longer in patients than in controls. On a gluten-free diet, surprisingly, the gastric emptying did not normalize despite an improvement of symptom score. No significant correlation between abnormal gastric emptying and specific symptom patterns, anthropometric parameters or severity of histological damage was found. Conclusions This finding supports the hypothesis that gluten-driven mucosal inflammation might determine motor abnormalities by affecting smooth muscle contractility or impairing gut hormone function. The persistence of these abnormalities on a gluten free diet suggests the presence of a persistent low-grade mucosal inflammation with a permanent perturbation of the neuro-immunomodulatory regulation.

Lactose malabsorption and intolerance: What should be the best clinical management?

Lactose malabsorption (LM) is the incomplete hydrolysis of lactose due to lactase deficiency, which may occur as a primary disorder or secondary to other intestinal diseases. Primary adult-type hypolactasia is an autosomal recessive condition resulting from the physiological decline of lactase activity. Different methods have been used to diagnose LM. Lactose breath test represents the most reliable technique. A recent consensus conference has proposed the more physiological dosage of 25 g of lactose and a standardized procedure for breath testing. Recently a new genetic test, based on C/T13910 polymorphism, has been proposed for the diagnosis of adult-type hypolactasia, complementing the role of breath testing. LM represents a well-known cause of abdominal symptoms although only some lactose malabsorbers are also intolerants. Diagnosing lactose intolerance is not straightforward. Many non-malabsorber subjects diagnose themselves as being lactose intolerant. Blind lactose challenge studies should be recommended to obtain objective results. Besides several studies indicate that subjects with lactose intolerance can ingest up to 15 g of lactose with no or minor symptoms. Therefore a therapeutic strategy consists of a lactose restricted diet avoiding the nutritional disadvantages of reduced calcium and vitamin intake.Various pharmacological options are also available. Unfortunately there is insufficient evidence that these therapies are effective. Further double-blind studies are needed to demonstrate treatment effectiveness in lactose intolerance.