Rebecca Burgell

Pathogenesis of Colonic Diverticulosis: Repainting the Picture

irst described in 1700, diverticulosis is now one of the most Fcommon gastrointestinal disorders in the Western world. More than 60% of adults older than age 60 have diverticulosis, with 4% to 25% of such individuals developing symptoms or complications (so-called diverticular disease). A plausible pathogenic hypothesis originally was proposed by Painter and Burkitt in 1971 (referred to here as Painter’s hypothesis). Consumption of a low-fiber diet results in small-volume, desiccated colonic contents that require the generation of high colonic pressures to progress toward the anus. High luminal pressures are thought to encourage the mucosa and submucosa to herniate through the circular muscle of the bowel at the point of greatest weakness, namely the site at which the blood vessels perforate the muscle layer, forming diverticulae. This pathogenic framework provides a ready explanation for the unequivocal association of diverticulosis with increasing age and Western lifestyle, and increasing prevalence in those migrating from a low-prevalence (African or Asian) to a high-prevalence (Western) region. It offers a simple preventive and possibly therapeutic option—increase dietary fiber intake. This tidy story, however, is being challenged. There are 4 key aspects that support Painter’s hypothesis. First, epidemiologic features of diverticular disease support a strong association with dietary fiber intake. Diverticular disease is common in Western societies where fiber intake is low (15 g in the typical American diet) but is very uncommon in Africa or Asia where fiber intake is generally higher (35 g in the typical African diet). Other ecologic evidence includes observations that vegetarians have half the risk of asymptomatic diverticular disease than nonvegetarians and are 31% less likely to be hospitalized with diverticular disease compared with meat eaters. There is a 41% lower risk in those eating more than 25 g fiber/d compared with those consuming less than 14 g/d. Second, colonic physiological studies have indicated that higher colonic pressures are found in patients with diverticulosis than in healthy individuals. Experimentally induced colonic pressure in Painter’s experiments “distended [existing] diverticula to an alarming degree.” Subsequent studies addressing this yielded both supporting and negative results, probably related to small sample size, heterogeneity of the conditions, and area of the bowel studied. However, in patients with diverticular disease, the addition of dietary fiber decreased colonic pressures, although whether this decreases diverticular formation is unknown. Third, studies in animal models have strongly supported the hypothesis. A low-fiber diet also is associated with decreased colonic transit and decreased stool weight. Colonic diverticula develop in response to lowbut not high-fiber diet in rats and in rabbits, where high colonic pressures were induced. The characteristic histopathologic changes associated with human diverticulosis, increased collagen and elastosis, also are observed in animals consuming a low-fiber diet. Fourth, several interventional studies have provided evidence in

The Lactulose Breath Test in Irritable Bowel Syndrome: Is It All Hot Air?

The microbial ecosystem that occupies the human intestine is essential for the maintenance of health. An intricate relationship exists between the gut microbiome, the central nervous system, the neuroimmune and neuroendocrine systems, the autonomic nervous system, and the enteric nervous system, the interplay of which is responsible for the effective control of the gut by the higher centers. The development of new techniques that enable better characterization of gut bacteria has noticeably increased interest how the human microbiome affects the development of disease, particularly so in the pathophysiology of functional gastrointestinal disorders, where epidemiological studies have long-linked acute gut infection with the development of chronic functional symptoms. Up to 30 % of patients develop irritable bowel syndrome (IBS) after suffering from a gastrointestinal infection, and 40 % describe symptomatic benefit from antibiotic therapy [1]. IBS has also been associated with altered diversity and composition of gut bacteria [2]. Although the exact mechanisms remain poorly defined, the gut microbiome is firmly associated with IBS pathogenesis. Given the presumed pathogenic role of the gut microbiota in IBS, its manipulation is now a ‘‘hot’’ topic in management, from the addition of ‘‘good bacteria’’ via probiotics, the promotion of ‘‘good bacteria’’ via prebiotics, the change of bacterial populations by antibiotics, and the replacement of bacteria via fecal microbiota transfer. Antibiotics have received the most attention since they are a major therapeutic tool in treating small intestinal bacterial overgrowth (SIBO), postulated to be an important link between gut bacteria and IBS. The small bowel normally contains only a fraction of the bacteria present in the large bowel (10 4 ‐10 8 vs. 10 9 ‐10 12 )[ 3]. SIBO, defined as an excess of colonic-type bacteria in the small bowel, is often diagnosed in patients with small bowel abnormalities such as altered anatomy, motility, or flow resulting in stasis, enhancing bacterial proliferation. While SIBO provides an attractive (and potentially treatable) cause for the symptoms of IBS, in reality diagnosing SIBO in IBS patients who have normal anatomy is fraught with controversy.

Endometriosis in patients with irritable bowel syndrome: Specific symptomatic and demographic profile, and response to the low FODMAP diet

Women with endometriosis are frequently misdiagnosed with irritable bowel syndrome (IBS) for some time before a correct diagnosis is made. Visceral hypersensitivity is a key feature in both conditions.

Illuminating dark depths

Microelectronic processing and engineered bacteria provide real-time insights into the gut The inner workings of human physiology remain one of the final frontiers of science. In particular, the gastrointestinal (GI) microenvironment is incompletely understood. On page 915 of this issue, Mimee et al. (1) have developed an ultralow-power ingestible sensor of various compounds (ingestible micro-bio-electronic device, IMBED) by combining engineered bioluminescent bacteria and microelectronic processing. This has the potential to unlock a wealth of information about the bodys structure and function, its relationship with the environment, and the impact of disease and therapeutic interventions.

Neuromodulation via Interferential Electrical Stimulation as a Novel Therapy in Gastrointestinal Motility Disorders

The concept of therapeutic percutaneous neuromodulation has, until recently, been limited by the ability to penetrate deeply enough to stimulate internal organs. By utilizing 2 medium frequency, slightly out of phase electrical currents passing diagonally through the abdomen, a third, low frequency current is created at the point of bisection. This interferential current appears to stimulate nerve fibers in the target organs and may have a therapeutic action. The aim of the study is to review the use of transcutaneous interferential electrical stimulation with a focus on its application in gastroenterology, particularly in motility disorders. Studies involving use of interferential current therapy were searched from Medline, PubMed, and Scopus databases, and articles pertaining to history, its application and all those treating abdominal and gastrointestinal disorders were retrieved. Seventeen studies were identified, 13 involved children only. Eleven of these were randomised controlled trials (3 in adults). Four trials were from the one center, where each paper reported on different outcomes such as soiling, defecation frequency, quality of life, and colon transit studies from the one pool of children. All studies found statistically significant improvement in symptom reduction. However, weaknesses in study design were apparent in some. In particular, finding an adequate placebo to interferential current therapy has been difficult. Interferential current therapy shows potential as a novel, non-pharmacological and economical means of treating gastrointestinal dysfunction such as constipation. More studies are needed particularly in the adult population. However, the design of a suitable placebo is challenging.

The safety and sensitivity of a telemetric capsule to monitor gastrointestinal hydrogen production in vivo in healthy subjects: a pilot trial comparison to concurrent breath analysis.

Intestinal gases are currently used for the diagnosis of disorders including small intestinal bacterial overgrowth and carbohydrate malabsorption.

Easing Concerns About the Low FODMAP Diet in Patients With Irritable Bowel Syndrome

76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 111 112 113 114 115 116 117 Dirritable bowel syndrome, because food is a major inducer of symptoms, and dietary manipulation empowers patients to influence the outcome of their disorder. It is not surprising, therefore, that the arrival of the low FODMAP diet, which is based on sound scientific evidence, has led to its enthusiastic adoption in clinical practice across the world. However, the diet has been criticized in 4 main areas: (1) the strength of the efficacy data, mainly owing to perceived bias in clinical trial design and the lack of realworld placebo-controlled trials; (2) the complexity and difficulty of teaching the diet; (3) safety, especially on the structure of gut microbiota; and (4) longer term efficacy and safety. The article by Staudacher et al in the current edition of Gastroenterology addresses three of these issues. Performance of high-quality, randomized, controlled trials of therapeutic diets is challenging. Theoretically, the standards by which we judge a dietary intervention should be as stringent as those for a pharmacological agent. Critics argue that such standards have not been adequately met for the low FODMAP diet. A gold standard approach for evaluating a therapeutic diet is the provision of all food to recipients in a double-blinded way, as was done in the pivotal study for the low FODMAP diet, with unequivocally positive results. Unfortunately, feeding studies do not mimic real-world clinical practice, where diets are taught by health professionals and implemented by patients. Dietitianled randomized, controlled trials have been conducted where comparator diets have ranged from habitual diet (which lacks the placebo effect of active dietitian-mediated intervention), high FODMAP diet (where potential exacerbation symptoms may exaggerate the efficacy of the low FODMAP diet), or currently administered active diets. All of these studies were designed to primarily address questions (effects on structure and function of gut microbiota, and on metabolomics profiles, and comparison with currently instituted therapies) other than efficacy over placebo. Furthermore, in the pivotal feeding study, the placebo diet was constructed on the basis of a typical intake of FODMAPs in healthy Australians, which proved to be greater than that retrospectively estimated from the participants’ habitual diet. Although the mean difference in oligosaccharide intake of 1.2 g/d was unlikely to induce symptoms, it may have confounding effects on the gut

Review article: dyssynergic defaecation and biofeedback therapy in the pathophysiology and management of functional constipation

Functional constipation is a common clinical presentation in primary care. Functional defaecation disorders are defined as the paradoxical contraction or inadequate relaxation of the pelvic floor muscles during attempted defaecation (dyssynergic defaecation) and/or inadequate propulsive forces during attempted defaecation. Prompt diagnosis and management of dyssynergic defaecation is hindered by uncertainty regarding nomenclature, diagnostic criteria, pathophysiology and efficacy of management options such as biofeedback therapy.

Sa2015 A Case Control Study Assessing the Symptomatic Impact of Rectal Hyposensitivity in Patients With Disordered Defecatory Function

Functional gastrointestinal (GI) disorders are common and are associated with a significant burden for affected individuals and society. Considering improvement in diagnostic and therapeutic options for patients with such diseases, we examined time trends in emergency department (ED) visits and hospitalization. METHODS: The Nationwide Inpatient Sample (NIS), the State Inpatient Database (SID) and Nationwide Emergency Department Sample (NEDS) were queried for annual encounters between 1997 and 2011 (2005-2011 for the NEDS), using diagnosis codes for constipation, irritable bowel syndrome (IBS), gastroesophageal reflux disease (GERD), dyspepsia and gastroparesis. Total case loads, age and sex distribution, and significant comorbid conditions were abstracted. RESULTS: Constipation accounted for about half of all ED encounters for all functional GI diseases with a 25% increase to an annual rate of 189.2±5.7 per 100,000. In the same time frame ED visits for gastroparesis nearly doubled (annual rate of 9.6±0.5/100,000), while visits for dyspepsia and GERD decreased or remained stable. Admission rates from the ED remained stable and were highest for gastroparesis (53.1±2.0%) followed by IBS (32.7±0.5%), GERD (17.4±0.8%), dyspepsia (9.4±0.2) and constipation (4.1±0.1%). Nearly 40% (38.6±0.6%) of ED encounters for constipation involved children, while the fraction of pediatric patients was significantly lower in all other functional GI diseases. Admission rates for constipation more than doubled to 12.0±0.5/100,000, while those for IBS transiently increased by 50% around 2004 and then dropped to 4.0±0.2/100,000. This pattern was seen across all regions of the United States. Abdominal pain was listed as secondary diagnosis in nearly one fifth of the patients, which did not differ significantly from IBS (18.1±0.8% vs. 20.2±0.9%, respectively). Mood disorders commonly coexisted and correlated with higher likelihood of hospitalization. CONCLUSION: Despite the widespread availability of treatment options, constipation remains a common reason for ED visits and hospitalizations, accounting for more than 50% of the encounters with functional gastrointestinal illnesses as the primary diagnosis. The striking shifts in the apparent burden of constipation and IBS likely represent differences in diagnostic coding. The lack of geographic difference suggests that national campaigns rather than graduate and post-graduate training of practitioners caused this shift.