The gut microbiome as a predictor of low fermentable oligosaccharides disaccharides monosaccharides and polyols diet efficacy in functional bowel disorders.

PURPOSE OF REVIEW: Fermentable oligosaccharides disaccharides monosaccharides and polyols (FODMAP) dietary restriction ameliorates irritable bowel syndrome (IBS) symptoms; however, not all individuals with IBS respond. Given the gut microbiome's role in carbohydrate fermentation, investigators have evaluated whether the gut microbiome may predict low FODMAP diet efficacy. RECENT FINDINGS: Gut microbiome fermentation, even to the same carbohydrate, is not uniform across all individuals with several factors (e.g. composition) playing a role. In both children and adults with IBS, studies are emerging suggesting the gut microbiome may predict low FODMAP diet efficacy. However, there is significant heterogeneity in the approaches (study population, microbiome assessment methods, statistical techniques, etc.) used amongst these studies. SUMMARY: The gut microbiome holds promise as a predictor of low FODMAP diet efficacy. However, further investigation using standardized approaches to evaluate the microbiome while concomitantly assessing other potential predictors are needed to more rigorously evaluate this area.

CHARGE syndrome gastrointestinal involvement: from mouth to anus.

CHARGE syndrome is an autosomal dominant disorder that occurs as a result of a heterozygous loss-of-function mutation in the chromodomain helicase DNA-binding (CHD7) gene, which is important for neural crest cell formation. Gastrointestinal (GI) symptoms and feeding difficulties are highly prevalent but are often a neglected area of diagnosis, treatment, and research. Cranial nerve dysfunction, craniofacial abnormalities, and other physical manifestations of this syndrome lead to gut dysmotility, sensory impairment, and oral-motor function abnormalities. Over 90% of children need tube feeding early in their life and many experience weak sucking/chewing, gastroesophageal reflux disease (GERD), and aspiration. The mainstay of treatment thus far has consisted of feeding therapy, GERD medications, Nissen fundoplication, gastrostomy/jejunostomy, and food texture limitation. Owing to the multitude of severe medical issues associated with this genetic disorder, GI involvement is often overlooked. Here, we report on five patients with CHARGE syndrome who manifested a range of severe GI and feeding difficulties.

Gastrointestinal manifestations in diploid/triploid mixoploidy.

A girl infant was delivered by cesarean section at 32 weeks of gestation because of growth arrest and poor movement patterns. The infant had feeding problems, which were based on gastroesophageal reflux, laryngomalacia, and decreased gut motility. Hypotonia was notable from the outset, and the patient eventually displayed significant delays in both motor and cognitive milestones. Meanwhile, lymphocytes had yielded a normal karyotype (46,XX), but at 2 years of age the patient underwent a skin biopsy and mosaicism because a 68,XX cell line was discovered in fibroblasts. At the age 6.4 years, the patient is short of stature below the 3rd percentile but has a weight at the 42nd percentile and head circumference above the 97th percentile. Other phenotypic features include low-set ears, piebald irides and scalp hair, eyelid ptosis, strabismus, broad nasal bridge, anteverted nares, upswept eyebrows, hypoplastic teeth, pectus excavatum, hypoplastic labia, scoliosis, 3-4 finger syndactyly, and 2-3 toe syndactyly. We present this case with a review of the literature for mixoploidy (the rare event of mosaicism for diploid and triploid cell lines). We add to the existing data on the clinical features of diploid/triploid mixoploidy. The complexities of the gastrointestinal problems make this case unusual.

A faculty development program integrating cross-cultural care into a gastrointestinal pathophysiology tutorial benefits students, tutors, and the course.

A specific faculty development program for tutors to teach cross-cultural care in a preclinical gastrointestinal pathophysiology course with weekly longitudinal followup sessions was designed in 2007 and conducted in the same manner over a 6-yr period. Anonymous student evaluations of how "frequently" the course and the tutor were actively teaching cross-cultural care were performed. The statements "This tutor actively teaches culturally competent care" and "Issues of culture and ethnicity were addressed" were significantly improved over baseline 2004 data. These increases were sustained over the 6-yr period. A tutor's overall rating as a teacher was moderately correlated with his/her "frequently" actively teaching cross-cultural care (r = 0.385, P < 0. 001). Course evaluation scores were excellent and put the course into the group of preclinical courses with the top ratings. Students in the Race in Curriculum Group asked that the program be expanded to other preclinical courses. In conclusion, from 2007 to 2012, a faculty development program for teaching cross-cultural care consistently increased the discussion of cross-cultural care in the tutorial and course over each year beginning with 2007 compared with the baseline year of 2004. Our data suggest that cross-cultural care can be effectively integrated into pathophysiology tutorials and helps improve students' satisfaction and tutors' ratings. Teaching cross-cultural care in a pathophysiology tutorial did not detract from the course's overall evaluations, which remained in the top group over the 6-yr period.

[Gastrointestinal features in systemic sclerosis]. / Manifestations digestives de la sclérodermie.

Systemic sclerosis (SSc) is a rare disorder associating vasculopathy, tissue fibrosis and autoimmunity. The gastro-intestinal tract (GIT) is frequently involved with any segment being potentially affected from mouth to anus. The esophagus is the most common localization resulting in reflux and its complications such as erosive esophagitis and Barrett's esophagus. Gastric involvement is less frequent but may be complicated by hemorrhage due to gastric antral vascular ectasia (GAVE or watermelon stomach). Intestinal involvement may lead to malabsorption, intestinal pseudo-obstruction or bacterial overgrowth. Anorectal involvement can cause fecal incontinence and rectal prolapse. GIT involvement greatly affects morbimortality in SSc and therapeutic approaches essentially aim at relieving the symptoms.

Non-nutritional effects of food: an underutilized and understudied therapeutic tool in chronic gastrointestinal diseases.

The use of diet has traditionally been used to improve the nutrition of patients. However, diet also can be utilized to modify disease processes and manage symptoms independently of its nutritional role. There are few chronic gastrointestinal conditions where dietary modification is utilized therapeutically and backed by a high degree of evidence. This is not due to a lack of ideas but is more likely to lie in the difficulties associated with translating those ideas into evidence-based practice. Long lead-in times and low incidence hinders interventional studies of prevention for many conditions. The design and execution of dietary clinical trials is challenging and funding them even more so. The knowledge base of doctors in nutrition and food composition is often poor, and attitudes toward the success of and adherence to dietary therapies create additional problems. However, ideas can be successfully translated into evidence-based practice, as exemplified but the low fermentable, oligo-, di-, and mono-saccharides and polyols (FODMAP) (poorly-absorbed short-chain carbohydrates) diet for patients with functional bowel symptoms. Showing efficacy is, however, insufficient for non-nutritional dietary manipulations. Adverse effects, such as nutritional adequacy of the diet and effect on pathogenesis of other diseases, must also be carefully addressed. The physiological principles upon which the diet is based should be matched to the physiology associated with the condition being targeted, as it can be hazardous to extrapolate findings in healthy persons. There is a need for greater attention to the evaluation of dietary therapies for many chronic gastrointestinal disorders.

Gastrointestinal and hepatic manifestations of Sjogren syndrome.

Sjogren syndrome (SS) is an autoimmune disease that affects exocrine glands and therefore may affect the gastrointestinal system, from the mouth, esophagus, and bowel to the liver and pancreas. Oral involvement in SS is mainly characterized by dryness, with a wide spectrum of symptoms, from mild-to-severe xerostomia with dysgeusia and tooth decay. The dysphagia, although common, does not correlate with the reduced salivary flow rate or the dysmotility that may be present. Dyspepsia, found in up to 23% of patients, may be associated with gastritis, reduced acid production, and antiparietal cell antibodies, but rarely pernicious anemia. Pancreatic involvement, although rare, includes pancreatitis and pancreatic insufficiency. The most common causes of liver disease are primary biliary cirrhosis, autoimmune hepatitis, nonalcoholic fatty liver disease, and hepatitis C virus (HCV). Although abnormal liver tests are found in up to 49% of patients, they are usually mild. Although sicca syndrome, abnormal histology of the salivary glands, and abnormal sialograms are common in primary biliary cirrhosis, the antibodies to Ro/SSA or La/SSB antigens are infrequent. Xerostomia, sialadenitis, abnormal salivary flow rates, and abnormal Schirmer test in HCV vary widely among the studies, although the antibodies to Ro/SSA or La/SSB are only 1%. Several studies show that HCV is in saliva, although how this may impact sicca syndrome or SS in HCV is unclear. SS as a disease of exocrine glands affects many parts of the gastrointestinal system.

Value of the Likert dyspepsia scale in differentiation of functional and organic dyspepsia in children.

AIM: Dyspeptic symptoms may not allow clinicians to differentiate organic and functional gastrointestinal disorders. According to our dyspeptic patients' answers to dyspepsia questionnaire, we aimed to define the symptom scores directing organic dyspepsia (OD) before upper gastrointestinal endoscopy. PATIENTS AND METHODS: One hundred sixty-one patients (ages 10-17 years, mean 13.5 ± 2.3 years, male/female: 2/3) with chronic upper gastrointestinal system symptoms lasting for at least 3 months were enrolled. Patients with predominated reflux symptoms were excluded by 24-hour pH monitoring. Before upper gastrointestinal endoscopy, severity and incidence of 8 gastrointestinal symptoms (epigastric pain, upper abdominal discomfort, retrosternal pyrosis, bitter or sour taste in mouth, halitosis, belching, nausea, and early satiety) were measured by 5-point Likert scale. Total score indicated severity score multiplied by incidence score. Antral biopsy samples were obtained. OD is defined as peptic ulcer, erosive esophagitis, erosive or nodular gastritis, and erosive duodenitis in endoscopy and/or moderate to severe antral gastritis in histology. Functional dyspepsia (FD) is defined as normal findings/mucosal hyperemia in endoscopy and/or mild antral gastritis in antral histology. We evaluated the relation among severity and incidence scores of each dyspeptic symptom in patients with OD or FD. Age, sex, body mass index, drug history, nutritional habits, the quality of life related to dyspepsia were also investigated in patients with OD and FD. RESULTS: According to patients' histological and endoscopic findings, 100 (62%) patients were in the OD group and 61 (38%) patients were in the FD group. Of the dyspeptic complaints, the severity, incidence, and total scores of epigastric pain were significantly correlated with dyspepsia type (respectively, P = 0.042, P = 0.028, and P = 0.005). Of 93 patients who had an epigastric pain severity of 4 and 5 (namely, moderate to severe pain), 65 (70%) patients were in the OD group and 28 (30%) patients were in the FD group. Of 68 patients who had an epigastric pain severity of 0 to 3 (no epigastric pain or mild pain), 33 (48.5%) were in the OD group and 35 (51.5%) were in the FD group, and the difference was statistically significant (P = 0.042). After analyzing the total scores of 8 dyspeptic symptoms, one by one or in different combinations, we could not find a threshold (cutoff) score value that was able to indicate OD definitely. Age, sex, body mass index, and nutritional habits were not significantly different between patients with OD or FD. Nocturnal abdominal pain, pain before meals, and resolution of symptoms after meals or ingestion of antacid drugs were not significantly related to OD. Nocturnal abdominal pain was observed to be higher in the group with moderate to severe gastric inflammation. CONCLUSIONS: In the present study, the severity, incidence, and total scores of epigastric pain were significantly related to OD; however, a cutoff value of dyspepsia symptom score for differentiation of OD and FD could not determined. In our study, Likert dyspepsia scale was not beneficial in differentiation of the OD/FD groups. We suggest that the Likert dyspepsia scale should be redesigned for children or the same scale should be applied in a larger cohort of dyspeptic children.

Sex differences feed into nuclear receptor signaling along the digestive tract.

Sex differences in physiology are noted in clinical and animal studies. However, mechanisms underlying these observed differences between males and females remain elusive. Nuclear receptors control a wide range of physiological pathways and are expressed in the gastrointestinal tract, including the mouth, stomach, liver and intestine. We investigated the literature pertaining to ER, AR, FXR, and PPAR regulation and highlight the sex differences in nutrient metabolism along the digestive system. We chose these nuclear receptors based on their metabolic functions, and hormonal actions. Intriguingly, we noted an overlap in target genes of ER and FXR that modulate mucosal integrity and GLP-1 secretion, whereas overlap in target genes of PPARα with ER and AR modulate lipid metabolism. Sex differences were seen not only in the basal expression of nuclear receptors, but also in activation as their endogenous ligand concentrations fluctuate depending on nutrient availability. Finally, in this review, we speculate that interactions between the nuclear receptors may influence overall metabolic decisions in the gastrointestinal tract in a sex-specific manner.

The Effect of the Low FODMAP Diet on Gastrointestinal Symptoms, Behavioral Problems and Nutrient Intake in Children with Autism Spectrum Disorder: A Randomized Controlled Pilot Trial.

Some research suggests that GI symptoms seen in children with ASD may relate to behavior problems. The objective of this pilot study was to assess the effect of the low fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) diet on GI and behavioral problems in children with ASD. At follow-up, the low FODMAP diet group had significant relief in some GI problems compared with both baseline in the group and control group. At baseline and at follow-up, there were no significant differences in behavioral problems between the low FODMAP diet group and the control group. Randomized controlled studies including larger sample sizes are needed to confirm the effects of low FODMAP diets in children with autism who have gastrointestinal problems.

Preoperative medical evaluation: part 2: pulmonary, endocrine, renal, and miscellaneous considerations.

A thorough assessment of a patient's medical status is standard practice when dental care is provided. Although this is true for procedures performed under local anesthesia alone, the information gathered may be viewed somewhat differently if the dentist is planning to provide sedation or general anesthesia as an adjunct to dental treatment. This article, the second of a 2-part sequence on preoperative assessment, will address pulmonary and other noncardiovascular disorders.

Lower gastrointestinal distress in endurance athletes.

Training regimens and race days place significant demands upon both the competitive endurance athlete and the frequent-recreational runner. Lower gastrointestinal derangements, especially those involving diarrhea and rectal bleeding, are common and can impact adversely both the performance and the health of the athlete. While most cases are relatively benign, more significant and severe symptoms may not only impair sports performance, but also signify more serious disease. The sports medicine clinician should be familiar with the management of these problems in order to optimize treatment, facilitate return to play, and maximize the athlete's potential.

Number of microvesicles in peripheral blood and ability of plasma to induce adhesion between phospholipid membranes in 19 patients with gastrointestinal diseases.

It was recently shown that the plasma protein-mediated attractive interaction between phospholipid membranes could in the budding process cause adhesion of the bud to the mother membrane [J. Urbanija, N. Tomsic, M. Lokar, A. Ambrozic, S. Cucnik, M. Kanduser, B. Rozman, A. Iglic, V. Kralj-Iglic, Coalescence of phospholipid membranes as a possible origin of anticoagulant effect of serum proteins, Chem. Phys. Lipids 150 (2007) 49-57]. Since in the in vivo conditions the budding of cell membranes leads to the release of microvesicles into the circulation, a hypothesis was put forward that the ability of plasma to cause adhesion between membranes supresses the microvesiculation process. In the present work, this hypothesis was tested in a population of 19 patients with gastrointestinal diseases. The number of microvesicles in peripheral blood of patients was determined by flow cytometry while the ability of plasma to cause adhesion between membranes was determined by adding patient's plasma to the suspension of giant phospholipid vesicles created by electroformation method, and measuring the average effective angle of contact between the adhered vesicles. Statistically significant negative correlations between the number of microvesicles and the average effective angle of contact (Pearson coefficient -0.50, p=0.031) and between the number of microvesicles per number of platelets and the average effective angle of contact (Pearson coefficient -0.64, p=0.003) were found, which is in favor of the above hypothesis. Patients with gastrointestinal cancer had larger number of microvesicles (difference 140%, statistical significance 0.033) and smaller average effective angle of contact (difference 20%, statistical significance 0.013) compared to patients with other gastrointestinal diseases.

Tachykinins in the gut. Part II. Roles in neural excitation, secretion and inflammation.

The preprotachykinin-A gene-derived peptides substance (substance P; SP) and neurokinin (NK) A are expressed in intrinsic enteric neurons, which supply all layers of the gut, and extrinsic primary afferent nerve fibers, which innervate primarily the arterial vascular system. The actions of tachykinins on the digestive effector systems are mediated by three different types of tachykinin receptor, termed NK1, NK2 and NK3 receptors. Within the enteric nervous system, SP and NKA are likely to mediate, or comediate, slow synaptic transmission and to modulate neuronal excitability via stimulation of NK3 and NK1 receptors. In the intestinal mucosa, tachykinins cause net secretion of fluid and electrolytes, and it appears as if SP and NKA play a messenger role in intramural secretory reflex pathways. Secretory processes in the salivary glands and pancreas are likewise influenced by tachykinins. The gastrointestinal arterial system may be dilated or constricted by tachykinins, whereas constriction and an increase in the vascular permeability are the only effects seen in the venous system. Various gastrointestinal disorders are associated with distinct changes in the tachykinin system, and there is increasing evidence that tachykinins participate in the hypersecretory, vascular and immunological disturbances associated with infection and inflammatory bowel disease. In a therapeutic perspective, it would seem conceivable that tachykinin antagonists could be exploited as antidiarrheal, antiinflammatory and antinociceptive drugs.

Basal and stimulated hypothalamic-pituitary-adrenal axis activity in patients with functional gastrointestinal disorders and healthy controls.

OBJECTIVE: The aim of this study was to investigate alterations of pituitary-adrenal activity under both stimulated and unstimulated conditions in patients with functional gastrointestinal disorders. METHODS: Thirty subjects who fulfilled the Rome Diagnostic Criteria for either irritable bowel syndrome or nonulcer dyspepsia and 24 healthy controls took part in the study. Free salivary morning cortisol and diurnal cortisol profiles were obtained for all subjects. On a second day, a low-dose dexamethasone suppression test was applied. Additionally, in all subjects a corticotropin-releasing hormone (CRH) challenge test was performed. RESULTS: The results show attenuated unstimulated cortisol levels in patients compared with controls. After CRH challenge, blunted adrenocorticotropic hormone and cortisol responses were observed. These findings suggest lower pituitary and adrenocortical activity in patients with functional gastrointestinal disorders. CONCLUSION: The observed pituitary-adrenal reactivity in these patients is discussed as a possible consequence of lower adrenocortical activity, possibly resulting in a disinhibition of CRH in the brain.

Severe anaphylactoid reactions to cuprammonium cellulose hemodialyzers.

Twenty-one severe reactions to hemodialysis occurred in approximately 260,000 dialysis treatments at three centers within a 10 1/2-year period. Reactions typically appeared within minutes of initiating dialysis, and were characterized by cardiopulmonary, mucocutaneous, and/or gastrointestinal tract symptoms highly suggestive of anaphylaxis. Four respiratory arrests and one death resulted. Analysis of dialyzer use patterns and of each patient's dialyzer exposure history strongly implicated hollow-fiber dialyzers made of cuprammonium cellulose (CC) as a cause of these reactions. No obvious factors could be found to identify predisposed patients. Less than optimal rinsing of the CC hollow-fiber dialyzers prior to use may have been responsible for some, but not all, of these reactions.

Gastrointestinal dysfunction in Parkinson's disease.

There is growing recognition that gastrointestinal dysfunction is common in Parkinson's disease (PD). Virtually all parts of the gastrointestinal tract can be affected, in some cases early in the disease course. Weight loss is common but poorly understood in people with PD. Dysphagia can result from dysfunction at the mouth, pharynx, and oesophagus and may predispose individuals to aspiration (accidental inhalation of food or liquid). Gastroparesis can produce various symptoms in patients with PD and may cause erratic absorption of drugs given to treat the disorder. Bowel dysfunction can consist of both slowed colonic transit with consequent reduced bowel-movement frequency, and difficulty with the act of defecation itself with excessive straining and incomplete emptying. Recognition of these gastrointestinal complications can lead to earlier and potentially more effective therapeutic intervention.

The use of glutamine in the treatment of gastrointestinal disorders in man.

The human gastrointestinal tract (GIT) is a major site of glutamine utilisation accounting for more than half of the net splanchnic utilisation (approximately 15 g/day) of glutamine obtained from the systemic circulation. Dietary glutamine (approximately 5 g/day) is less important than circulating glutamine, especially in disease conditions associated with substantial reduction in food intake. Glutamine has multiple effects on the structure and function of the GIT, and effects in improving morbidity and mortality in animal models of GIT damage has led to a series of studies in man, which have produced variable results. Glutamine administration to treat mucositis of the upper GIT (mouth, oesophagus) due to cytotoxic drug therapy, has produced no evidence of benefit. Early studies suggested improved healing, as do recent studies of small intestinal mucositis resulting from chemotherapy. Investigations in colitis are lacking although in experimental rat models of colitis no benefit has been reported. Multiple explanations can be put forward to explain the overall results, including the GIT distribution of enzymes involved in glutamine metabolism. Apart from the lower stomach in man (upper stomach in the rat) there is very little weak activity of glutamine synthetase, suggesting that the gut derives glutamine formed in other tissues and from the diet. The activity of glutaminase, which is key flux generating enzyme involved in glutaminolysis is very weak in mucosa with stratified squamous epithelium (oesophagus), where intermediate in the same intestine, and highest in the small intestinal mucosa which accounts for about 80% of the total glutaminase in the entire human GIT mucosa.

Rate and pattern of gastric emptying in humans using 99mTc-labeled triethylenetetraamine-polystyrene resin.

The preparation and application of a new radiopharmaceutical used in the investigation of the rate and pattern of gastric emptying by external scintigraphy are described. Triethylenetetraamine was bound covalently to cross-linked chloromethylated polystyrene. The triethylenetetraamine-polystyrene resin tenaciously and rapidly bound technetium 99m. The gastric emptying rate was evaluated in normal adult volunteers and patients by serially recording the gastric radioactivity after ingestion of a test meal mixed with 99mTc-labeled triethylenetetraamine-polystyrene resin. The data indicated that 99mTc-labeled triethylenetetraamine-polystyrene resin was an ideal agent for assessing the rate and pattern of gastric emptying in humans. The gastric emptying half-time (t 1/2 GE) in normal subjects ranged from 25 to 75 min.