Paul Enck

Minimum standards of anorectal manometry

Functional disorders of the anus and rectum affect 10–20% of the population. Tests of anorectal function can provide useful information regarding the pathophysiology of disorders that affect continence and defecation or those that cause anorectal pain. Currently, several tests are available for evaluating anorectal function (Table 1). Often, they complement each other, but among the various tests that are available, the two most commonly performed tests are: (i) anorectal manometry and (ii) the balloon expulsion test. Recent studies suggest that manometric tests can be useful in the management of defecation disorders. The diagnostic potential and yield of these tests have been described previously. However, there is lack of uniformity with regard to the methods of performance and interpretation of the tests. There is also a relative lack of normative data stratified for age and gender. Individual laboratories are therefore encouraged to either consult published data or establish their own normative data. Purpose

A vegan or vegetarian diet substantially alters the human colonic faecal microbiota

Background/Objectives:Consisting of ∼1014 microbial cells, the intestinal microbiota represents the largest and the most complex microbial community inhabiting the human body. However, the influence of regular diets on the microbiota is widely unknown.Subjects/Methods:We examined faecal samples of vegetarians (n=144), vegans (n=105) and an equal number of control subjects consuming ordinary omnivorous diet who were matched for age and gender. We used classical bacteriological isolation, identification and enumeration of the main anaerobic and aerobic bacterial genera and computed absolute and relative numbers that were compared between groups.Results:Total counts of Bacteroides spp., Bifidobacterium spp., Escherichia coli and Enterobacteriaceae spp. were significantly lower (P=0.001, P=0.002, P=0.006 and P=0.008, respectively) in vegan samples than in controls, whereas others (E. coli biovars, Klebsiella spp., Enterobacter spp., other Enterobacteriaceae, Enterococcus spp., Lactobacillus spp., Citrobacter spp. and Clostridium spp.) were not. Subjects on a vegetarian diet ranked between vegans and controls. The total microbial count did not differ between the groups. In addition, subjects on a vegan or vegetarian diet showed significantly (P=0.0001) lower stool pH than did controls, and stool pH and counts of E. coli and Enterobacteriaceae were significantly correlated across all subgroups.Conclusions:Maintaining a strict vegan or vegetarian diet results in a significant shift in the microbiota while total cell numbers remain unaltered.

Affective disturbances modulate the neural processing of visceral pain stimuli in irritable bowel syndrome: an fMRI study

Objective To address the role of anxiety and depression symptoms in altered pain processing in irritable bowel syndrome (IBS). Design In this functional magnetic resonance imaging study, the blood oxygen level-dependent (BOLD) response to rectal distensions delivered at previously determined individual discomfort thresholds was assessed. Patients 15 female patients with irritable bowel syndrome (IBS) and with normal rectal pain thresholds, and 12 healthy women. Measures The correlation of anxiety and depression symptoms, measured with the Hospital Anxiety and Depression Scale (HADS), with subjective pain ratings and the BOLD response during distension-induced brain activation were analysed within IBS. Group differences in pain-induced brain activation with and without controlling for HADS scores were evaluated. Results Patients with IBS experienced significantly more pain and discomfort upon rectal distensions in the scanner, despite unaltered rectal sensory thresholds. Anxiety and depression scores were associated with these subjective stimulus ratings, but not with rectal sensory thresholds. Anxiety symptoms in IBS were significantly associated with pain-induced activation of the anterior midcingulate cortex and pregenual anterior cingulate cortex. Depression scores correlated with activation of the prefrontal cortex (PFC) and cerebellar areas within IBS. Group comparisons with the two-sample t test revealed significant activation in the IBS versus controls contrast in the anterior insular cortex and PFC. Inclusion of anxiety and depression scores, respectively, as confounding variables led to a loss of significant group differences. Conclusions Altered central processing of visceral stimuli in IBS is at least in part mediated by symptoms of anxiety and depression, which may modulate the affective–motivational aspects of the pain response.

Anorectal functional testing: review of collective experience.

Anorectal manometry includes a number of specific tests that are helpful in the diagnostic assessment of patients with fecal incontinence and constipation; their purpose is to delineate the pathophysiological mechanism for these symptoms. Some of these tests may also provide helpful information in the assessment of patients with rectal pain or diarrhea, but their sensitivity and specificity are less well established for these symptoms. Tests for which there is consensus regarding their clinical utility include 1) resting anal canal pressure, 2) anal canal squeeze pressure (peak pressure and duration), 3) the rectoanal inhibitory reflex elicited by balloon distension of the rectum, 4) anal canal pressure in response to a cough, 5) anal canal pressure in response to defecatory maneuvers, 6) simulated defecation by means of balloon or radiopaque contrast, 7) compliance of the rectum in response to balloon distension, and 8) sensory thresholds in response to balloon distension. Anal endosonography and pelvic floor electromyography from intra-anal plate electrodes are nonmanometric tests that are also specifically useful in the evaluation of constipation and fecal incontinence. The clinical utility of all anorectal manometric tests is limited by the relative absence of 1) standardization of test protocols and 2) normative data from a large number of healthy individuals. The interpretation of these diagnostic tests is also complicated by the fact that patients are able to compensate for deficits in specific physiological mechanisms maintaining continence and defecation by utilizing other biological and behavioral mechanisms.

Acupuncture treatment in irritable bowel syndrome

Background and aims: Despite occasional positive reports on the efficacy of acupuncture (AC) on functions of the gastrointestinal tract, there is no conclusive evidence that AC is effective in the treatment of irritable bowel syndrome (IBS). Patients and methods: Forty three patients with IBS according to the Rome II criteria were randomly assigned to receive either AC (n = 22) or sham acupuncture (SAC) (n = 21) using the so-called “Streitberger needle”. Treatment duration was 10 sessions with an average of two AC sessions per week. The primary end point was improvement in quality of life (QOL) using the functional digestive diseases quality of life questionnaire (FDDQL) and a general quality of life questionnaire (SF-36), compared with baseline assessments. QOL measurements were repeated three months after treatment. Results: Both the AC and SAC groups improved significantly in global QOL, as assessed by the FDDQL, at the end of treatment (p = 0.022), with no differences between the groups. SF-36 was insensitive to these changes (except for pain). This effect was partially reversed three months later. Post hoc comparison of responders and non-responders in both groups combined revealed a significant prediction of the placebo response by two subscales of the FDDQL (sleep, coping) (F = 6.746, p = 0.003) in a stepwise regression model. Conclusions: Acupuncture in IBS is primarily a placebo response. Based on the small differences found between the AC and SAC groups, a study including 566 patients would be necessary to prove the efficacy of AC over SAC. The placebo response may be predicted by high coping capacity and low sleep quality in individual patients.

Functional neuroimaging of visceral sensation.

Summary The use of functional brain imaging techniques has led to considerable advances in our understanding of brain processing of human visceral sensation. The use of complementary techniques such as functional MRI, positron emission tomography, magnetoencephalography, and EEG has led to the identification of a network of brain areas that process visceral sensation. These studies suggest that unlike somatic sensation, which has an intense homuncular representation in the primary somatosensory cortex (SI), visceral sensation is primarily represented in the secondary somatosensory cortex, whereas representation in SI is vague. This difference could account for the poor localization of visceral sensation in comparison with somatic sensation. However, in a manner similar to that of somatic sensation, visceral sensation is represented in the paralimbic and limbic structures such as the insular, anterior cingulate, and prefrontal cortices. These areas are likely to mediate the affective and cognitive components of visceral sensation. Recent studies suggest that negative emotional factors such as fear, and cognitive factors such as attention can modulate the brain processing of visceral sensation in the insular and anterior cingulate cortices. In addition, alterations in the pattern of cortical processing of visceral sensation have been described in patients with functional gastrointestinal pain. It is likely that future research into the factors that modulate the brain processing of visceral sensation in health and disease are likely to improve further our understanding of the pathophysiology of functional visceral pain disorders.

Intestinal Microbiota And Diet in IBS: Causes, Consequences, or Epiphenomena?

Irritable bowel syndrome (IBS) is a heterogeneous functional disorder with a multifactorial etiology that involves the interplay of both host and environmental factors. Among environmental factors relevant for IBS etiology, the diet stands out given that the majority of IBS patients report their symptoms to be triggered by meals or specific foods. The diet provides substrates for microbial fermentation, and, as the composition of the intestinal microbiota is disturbed in IBS patients, the link between diet, microbiota composition, and microbial fermentation products might have an essential role in IBS etiology. In this review, we summarize current evidence regarding the impact of diet and the intestinal microbiota on IBS symptoms, as well as the reported interactions between diet and the microbiota composition. On the basis of the existing data, we suggest pathways (mechanisms) by which diet components, via the microbial fermentation, could trigger IBS symptoms. Finally, this review provides recommendations for future studies that would enable elucidation of the role of diet and microbiota and how these factors may be (inter)related in the pathophysiology of IBS.

Irritable Bowel Syndrome

Irritable bowel syndrome (IBS) is a functional gastrointestinal disease with a high population prevalence. The disorder can be debilitating in some patients, whereas others may have mild or moderate symptoms. The most important single risk factors are female sex, younger age and preceding gastrointestinal infections. Clinical symptoms of IBS include abdominal pain or discomfort, stool irregularities and bloating, as well as other somatic, visceral and psychiatric comorbidities. Currently, the diagnosis of IBS is based on symptoms and the exclusion of other organic diseases, and therapy includes drug treatment of the predominant symptoms, nutrition and psychotherapy. Although the underlying pathogenesis is far from understood, aetiological factors include increased epithelial hyperpermeability, dysbiosis, inflammation, visceral hypersensitivity, epigenetics and genetics, and altered brain–gut interactions. IBS considerably affects quality of life and imposes a profound burden on patients, physicians and the health-care system. The past decade has seen remarkable progress in our understanding of functional bowel disorders such as IBS that will be summarized in this Primer.

The placebo response in clinical trials: more questions than answers

Meta-analyses and re-analyses of trial data have not been able to answer some of the essential questions that would allow prediction of placebo responses in clinical trials. We will confront these questions with current empirical evidence. The most important question asks whether the placebo response rates in the drug arm and in the placebo arm are equal. This ‘additive model’ is a general assumption in almost all placebo-controlled drug trials but has rarely been tested. Secondly, we would like to address whether the placebo response is a function of the likelihood of receiving drug/placebo. Evidence suggests that the number of study arms in a trial may determine the size of the placebo and the drug response. Thirdly, we ask what the size of the placebo response is in ‘comparator’ studies with a direct comparison of a (novel) drug against another drug. Meta-analytic and experimental evidence suggests that comparator studies may produce higher placebo response rates when compared with placebo-controlled trials. Finally, we address the placebo response rate outside the laboratory and outside of trials in clinical routine. This question poses a serious challenge whether the drug response in trials can be taken as evidence of drug effects in clinical routine.

Brain imaging of visceral functions in healthy volunteers and IBS patients

From experience, most people know about a link between psychological processes and gastrointestinal sensory and motor functions. Cognitive processes (e.g., attention) as well as affective processes (e.g., fear) play a role in gastrointestinal sensations in healthy controls and patients with irritable bowel syndrome (IBS) alike. However, the exact nature of this relationship has not been completely understood yet. Brain imaging techniques allow for the study of brain-gut interactions in vivo. Accordingly, positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) have been widely used to study neural mechanisms underlying visceral sensations. This article will summarize the results of functional brain imaging studies in healthy controls and selected studies assessing the influence of psychological processes on gastrointestinal functions. Subsequently, this article will deal with those brain areas activated by visceral stimulation in IBS patients. Special attention will be paid to recently published studies concerning psychological factors and novel research questions.