Cause Of Irritable Bowel Syndrome Research Articles

137: Altered Th1-Th2 response during infection is predictive for development of post-infectious Irritable Bowel Syndrome

Aims Irritable Bowel Syndrome (IBS) is a gastrointestinal disorder with symptoms including abdominal pain, bloating and alteration of bowel habit. The causes of IBS are unknown, but due to the high incidence, IBS is becoming a burden to primary health care. Contrasting reports on immune dynamics underlying IBS development exist, and it is unclear whether there is immune activation or Th2-dominant responses in IBS individuals. Here, we performed a prospective study to investigate the involvement of the immune system in post-infectious IBS (PI-IBS) development and to characterise differences in the immune responses between IBS patients and healthy controls. Methods Blood was collected shortly after (n = 54) and one year after gastrointestinal infection (n = 143). Twenty cell subsets were analysed including CD4/CD8 T-cell subsets, γδ T-cells, B-cell subsets, DC, NK and NKT cells. Additionally, expression of IL-4, IL-5, IL-6, IL-8, IL-10, IL-17, TNFα, TNFγ and TGFβ was quantified by qPCR in rectal biopsies taken at one year post-infection. IL1β, IL-8, TNF-α, IL-13 and IL-10 levels were also measured in the supernatant of stimulated lymphocytes using Cytometric Bead Array technique. All participants answered questionnaires at both time points and were invited for interviews to confirm their health status at one year post-infection. Results Immune phenotyping revealed elevated Th2 responses (p = 0.0283) during gastrointestinal infection in individuals that developed PI-IBS. In addition, a decrease in CD4 + IL2 + cells (p = 0.0379) correlated with a reduction in Tregs in these individuals in the initial phase. However, at one year post-infection, there was no significant difference in the systemic immune system between PI-IBS individuals and controls. Similarly, there was no sign of local immune activation in biopsies of PI-IBS individuals with ongoing symptoms. Conclusions Increased Th2 response in peripheral immune system during gastrointestinal infection represents a predisposed factor for developing post-infectious IBS. However, after the establishment of IBS, the systemic immune phenotypes normalise.

A study of the methodological and clinical validity of the combined lactulose hydrogen breath test with scintigraphic oro‐cecal transit test for diagnosing small intestinal bacterial overgrowth in IBS patients

Small intestinal bacterial overgrowth (SIBO) may be a cause of irritable bowel syndrome (IBS); however, current investigations have important limitations. We aimed to identify clinically relevant diagnostic criteria for SIBO based on lactulose hydrogen breath test (LHBT) alone and combined with scintigraphic measurement of oro-cecal transit (SOCT). Results of LHBT/SOCT investigation from 89 IBS patients and 13 healthy volunteers were included in a systematic analysis of six published criteria for SIBO diagnosis. Clinical relevance of competing criteria was determined by assessing (i) prevalence of SIBO in IBS patients and healthy volunteers (ii) if SIBO diagnosis predicted improvement in IBS symptoms in a prospective, pilot therapeutic trial of a non-absorbable antibiotic (rifaximin 600mg b.d.) in IBS patients. Reproducibility of SIBO diagnosis by combined LHBT/SOCT was near perfect. A ≥5ppm H2 increase prior to appearance of cecal contrast was detected in more IBS patients than healthy volunteers (35/89 vs 1/13; p=0.026), but not for other diagnostic criteria. IBS patients with SIBO, compared to those without SIBO, reported significantly greater improvement in abdominal symptoms following rifaximin therapy (p<0.002 overall IBS symptom severity). This improvement was most marked in D-IBS patients in whom all symptoms improved, including stool frequency and consistency (all p<0.004). Combined LHBT/SOCT testing using a H2 5ppm cutoff may identify a subgroup of IBS patients with SIBO. Pilot data examining the clinical response to rifaximin suggest that this subset of IBS patients may benefit more than those with a normal test.

Irritable bowel syndrome: pathogenesis, diagnosis, treatment, and evidence-based medicine.

Irritable bowel syndrome (IBS) is a chronic and debilitating functional gastrointestinal disorder that affects 9%-23% of the population across the world. The percentage of patients seeking health care related to IBS approaches 12% in primary care practices and is by far the largest subgroup seen in gastroenterology clinics. It has been well documented that these patients exhibit a poorer quality of life and utilize the health care system to a greater degree than patients without this diagnosis. The pathophysiology of IBS is not clear. Many theories have been put forward, but the exact cause of IBS is still uncertain. According to the updated ROME III criteria, IBS is a clinical diagnosis and presents as one of the three predominant subtypes: (1) IBS with constipation (IBS-C); (2) IBS with diarrhea (IBS-D); and (3) mixed IBS (IBS-M); former ROME definitions refer to IBS-M as alternating IBS (IBS-A). Across the IBS subtypes, the presentation of symptoms may vary among patients and change over time. Patients report the most distressing symptoms to be abdominal pain, straining, myalgias, urgency, bloating and feelings of serious illness. The complexity and diversity of IBS presentation makes treatment difficult. Although there are reviews and guidelines for treating IBS, they focus on the efficacy of medications for IBS symptoms using high-priority endpoints, leaving those of lower priority largely unreported. Therefore, the aim of this review is to provide a comprehensive evidence-based review of the diagnosis, pathogenesis and treatment to guide clinicians diagnosing and treating their patients.

A common cause of irritable bowel syndrome and diverticulitis: chronic distal colon distention from sedentary behavior and excessive dietary fiber

A multidisciplinary analysis restricted to validated reports was applied to the cause and management of irritable bowel syndrome and diverticular formation and subsequent diverticulitis. There is evidence that they are linked – both caused by attenuation of gravitational aid to distal intestinal motility, resulting in damaging chronic intestinal distention. Both irritable bowel syndrome and diverticular formation and subsequent diverticulitis have worsened in recent years owing to excessive dietary fiber intake. Potential solutions include augmenting weight-bearing time, moderating dietary fiber consumption, stimulating distal colon evacuation through chemical means and developing pharmaceuticals to block the reflexive distal colon distention associated with fiber consumption. Amplified intestinal distention commenced when all classes of Renaissance Europeans became the first group in human history to wear shoes, which led to a sedentary lifestyle that moderates gravitational aid to colon motility and evacuation.

Irritable bowel syndrome in Chinese nursing and medical school students—Related lifestyle and psychological factors

Background: Previous studies have shown that the prevalence of irritable bowel syndrome (IBS) is 10% - 15% in the general population. IBS is a functional gastrointestinal disorder characterized by abdominal pain, abdominal discomfort and disordered defecation associated with a stressful lifestyle. However, the cause of IBS has not been clarified yet. Based on a similar, previous study in Japan, this study investigated the prevalence of IBS and the relationship between IBS and stress, lifestyle and dietary habits among nursing and medical school students in China. Methods: Designed to investigate IBS symptoms, life- style, dietary intake, life events, anxiety and depresssion, a blank self-administrated questionnaire was used to survey 2500 nursing or medical students in China. Questionnaires were collected from 2141 stu- dents (85.6%) and responses obtained from 1934 students (90.3%) were analyzed. Results: On the whole, the prevalence of IBS was 32.1% in this study, 26.6% in males and 33.6% in females. In females, the IBS group showed a bedtime later than that in the non-IBS group, and the length of time asleep in the IBS group was shorter than that in the non-IBS group (p p = 0.005). In females, the IBS group showed a frequency for the intake of vegetables and potatoes that was lower than that of the non-IBS group (p = 0.007, p = 0.023). The prevalence of IBS among nursing and medical school students in China (32.1%) was significantly lower than that in Japan (35.5%). Especially, the number of females in the constipation dominant IBS subgroup in China (11.8%) was less than that found in Japan (20.4%). Conclusions: The prevalence of IBS was high among nursing and medical students in China, but lower than that shown in Japan.

Novel insights which may translate into treatments for irritable bowel syndrome

Novel insights which may translate into treatments for irritable bowel syndrome

Irritable bowel syndrome: Diagnosis and pathogenesis

Irritable bowel syndrome (IBS) is a common gastrointestinal (GI) disorder that considerably reduces the quality of life. It further represents an economic burden on society due to the high consumption of healthcare resources and the non-productivity of IBS patients. The diagnosis of IBS is based on symptom assessment and the Rome III criteria. A combination of the Rome III criteria, a physical examination, blood tests, gastroscopy and colonoscopy with biopsies is believed to be necessary for diagnosis. Duodenal chromogranin A cell density is a promising biomarker for the diagnosis of IBS. The pathogenesis of IBS seems to be multifactorial, with the following factors playing a central role in the pathogenesis of IBS: heritability and genetics, dietary/intestinal microbiota, low-grade inflammation, and disturbances in the neuroendocrine system (NES) of the gut. One hypothesis proposes that the cause of IBS is an altered NES, which would cause abnormal GI motility, secretions and sensation. All of these abnormalities are characteristic of IBS. Alterations in the NES could be the result of one or more of the following: genetic factors, dietary intake, intestinal flora, or low-grade inflammation. Post-infectious IBS (PI-IBS) and inflammatory bowel disease-associated IBS (IBD-IBS) represent a considerable subset of IBS cases. Patients with PI- and IBD-IBS exhibit low-grade mucosal inflammation, as well as abnormalities in the NES of the gut.

Imbalanced shift of cytokine expression between T helper 1 and T helper 2 (Th1/Th2) in intestinal mucosa of patients with post-infectious irritable bowel syndrome

BackgroundIrritable bowel syndrome (IBS) is a common functional bowel disorder. The post-infectious IBS (PI-IBS) occurs in IBS patients with a history of intestinal infection preceding the onset of symptoms. However, the underlying cause of PI-IBS is not fully understood, and the purpose of this study was to investigate the immune regulatory mechanism of PI-IBS.MethodsParticipants enrolled in this study were divided into three groups including PI-IBS patients (n = 20), IBS patients without a history of infection (non-PI-IBS, n = 18), and healthy controls (n = 20). The expression levels of the Th1-derived cytokines IFN-γ and IL-12, and the Th2-derived cytokines IL-4 and IL-10 in the mucosal specimens, and in the ascending colon, the descending colon, and the rectal segments were measured by RT-PCR and western blot.ResultsThe IFN-γ mRNA levels in the intestinal mucosa were significantly higher in the PI-IBS group than in the non-PI-IBS or control group (both P < 0.05), but there was no difference between the non-PI-IBS and control groups. A trend toward IFN-γ protein upregulation was found in the PI-IBS group, while the IL-12 and IL-4 mRNA and protein levels were not different between any groups. The IL-10 mRNA and protein levels in the PI-IBS group were both significantly lower than in the non-PI-IBS or control groups (P < 0.05, respectively), but there was no difference between the non-PI-IBS and control groups. There were no differences in the cytokine mRNA and protein levels among the ascending colon, the descending colon, and the rectum of all groups.ConclusionsAn increase in IFN-γ levels and a decrease in IL-10 levels were found in the intestinal mucosa of PI-IBS patients, suggesting that the infection may affect the Th1/Th2 balance. Thus, the dysregulation of the immune response is likely an important cause of IBS.

Can a Mathematical Model Be Used to Estimate the Contribution of Acute Gastroenteritis to the Overall Prevalence of Irritable Bowel Syndrome?

Can a Mathematical Model Be Used to Estimate the Contribution of Acute Gastroenteritis to the Overall Prevalence of Irritable Bowel Syndrome?

CME Activities—Exams 1 and 2

Questioning the Bacterial Overgrowth Hypothesis of Irritable Bowel Syndrome: An Epidemiologic and Evolutionary PerspectiveClinical Gastroenterology and HepatologyVol. 9Issue 6PreviewAlthough studies indicate that small intestinal bacterial overgrowth (SIBO) is prevalent in irritable bowel syndrome (IBS), it remains unclear whether SIBO causes IBS. This review presents an epidemiologic and evolutionary inquiry that questions the bacterial overgrowth hypothesis of IBS, as follows. (1) Although the hypothesis may be biologically plausible, there is also a strong rationale for competing hypotheses; it is unlikely that SIBO is the predominant cause of IBS in all comers, because competing explanations are sensible and defensible. Full-Text PDF

Rifaximin Offers Symptom Relief for IBS Without Constipation

A pair of clinical trials has found that 2 weeks of treatment with the minimally absorbed antibiotic, rifaximin, provides significant relief of irritable bowel syndrome (IBS) symptoms. In addition, the studies found that the benefits of treatment with rifaximin persisted for 10 weeks after patients stopped taking the antibiotic, said Yehuda Ringel, MD, Associate Professor of Medicine in the University of North Carolina School of Medicine and a co-author of the studies, which were published in the January 6, 2011, issue of The New England Journal of Medicine. “These results support the idea that intestinal microbiota may be an underlying cause of IBS, and altering gut bacteria by treatment with rifaximin appears to be an effective way of providing relief to those who suffer from IBS symptoms,” Dr Ringel says. Patients in the study reported relief of their symptoms that extended for weeks after completing treatment with rifaximin. Specifically, they reported relief from bloating, less abdominal pain, and improved stool consistency for up to 10 weeks. Although the concept of bacteria playing a key role in IBS pathophysiology was controversial when first unveiled a decade ago, research confirms that gut flora trigger IBS symptoms. The findings also show that targeted antibiotics provide safe, effective, long-lasting relief for this condition, said Mark Pimentel, MD, GI Motility Program director and principal investigator of the clinical trial at Cedars–Sinai Medical Center in Los Angeles. The 2 studies, known as TARGET 1 and TARGET 2, were conducted in parallel from June 2008 through June 2009. In the studies, a total of 1260 patients who had IBS without constipation were enrolled at one of 179 study sites in the United States and Canada. All were randomized to receive the study drug in 550-mg doses, 3 times daily for 2 weeks, or placebo. All were then followed for an additional 10 weeks. Adequate relief was defined as self-reported relief of symptoms for ≥2 of the first 4 weeks after treatment. Other secondary end points included the percentage of patients who had a response to treatment as assessed by daily self-ratings of global IBS symptoms and individual symptoms of bloating, abdominal pain, and stool consistency during the 4 weeks after treatment and during the entire 3 months of the study. Significantly more patients in the rifaximin group than in the placebo group had adequate relief of global IBS symptoms during the first 4 weeks after treatment (40.8% vs 31.2% [P = .01], in TARGET 1; 40.6% vs 32.2% [P = .03] in TARGET 2; and 40.7% vs 31.7% [P < .001] in the 2 studies combined). Similarly, more patients in the rifaximin group than in the placebo group had adequate relief of bloating (39.5% vs 28.7% [P = .005] in TARGET 1; 41.0% vs 31.9% [P = .02], in TARGET 2; and 40.2% vs 30.3% [P < .001] in the 2 studies combined) and significantly more patients in the rifaximin group had a response to treatment as assessed by daily ratings of IBS symptoms, bloating, abdominal pain, and stool consistency. The incidence of adverse events was similar in the 2 groups. The studies concluded that 550-mg doses of rifaximin taken 3 times a day for 14 days provides better relief of IBS symptoms than placebo for up to 10 weeks after completion of therapy. “These studies support the idea that gut bacteria have an important role in maintaining normal intestinal function and emphasize the need for further research on the interaction between the intestinal microbiota and the human host,” Dr Ringel says.

Mucosal inflammation as a potential etiological factor in irritable bowel syndrome: a systematic review

The causes of irritable bowel syndrome (IBS) remain obscure. Some investigators have proposed chronic low-grade mucosal inflammation as a potential etiological factor. We performed a systematic review to examine this issue in detail. MEDLINE, EMBASE, and EMBASE classic were searched up to December 2010 to identify studies of case-control design applying tests for low-grade inflammation to either full-thickness intestinal or endoscopic mucosal biopsies from patients with IBS. Controls were required to be healthy individuals, or asymptomatic patients undergoing investigation for reasons other than the reporting of upper or lower gastrointestinal symptoms. Individual study results were summarized descriptively. The literature search identified 1388 citations, of which 16 studies were eligible for inclusion. Individual study results were diverse, partly as a consequence of the different surrogate markers for inflammatory mechanisms studied. Mast cells, T lymphocytes, B lymphocytes, and mucosal cytokine production all appeared altered among cases with IBS in individual studies, while no study demonstrated a significant difference in numbers of plasma cells, neutrophils, or eosinophils. Some studies suggested a relationship between mast cell abnormalities and symptom severity and frequency, as well as co-existent fatigue and depression. Studies were limited by the lack of comparability of controls, and the fact that most were conducted in highly selected groups of patients with IBS. Low-grade mucosal inflammation, particularly mast cell activation, may be a contributory factor in the pathogenesis of IBS. Mast cell stabilizers warrant further assessment as a potential therapy in the condition.

Book Review: Gas Biology Research in Clinical Practice, edited by Toshikazu Yoshikawa and Yuji Naito

Gaseous substances constitute a unique class of indispensable biomaterials for maintaining the homeostasis of biological systems. In particular, the gases, including nitric oxide (NO), carbon monoxide (CO), hydrogen sulfide (H2S), and hydrogen (H2), have well been described in the last decade as signaling gas molecules, as well as other important candidates for clinical applications. Given the fact that those individual gases play critical roles in biological systems, providing the newest findings and applications for gas biology basic and clinical research is of great importance. This book provides valuable information not only for basic researchers in physiology and biochemistry, but also for clinicians who wish to learn more about the role of gaseous mediators. This book has been published with 32 figures and 11 tables and divided into a preface and seven sections, listed below. In each section, leading specialists share their scientific experience in the field, covering a wide range of topics, including genetic, physiological, and medical imaging techniques. In each chapter, the authors take the reader on a vast journey through the impressive recent advances in gas biology (Figure 1). The preface provides the background and acknowledgements. Drs. Yoshikawa and Naito have held annual meetings entitled “Heme Oxygenase Research Forums” since 2004. These conferences largely expanded and encouraged CO research, which was generated in the process of heme degradation by heme oxygenase. The idea of organizing this type of book was initiated by Dr. Hideo Ueda, who has been ill for years. As the subject matter of this book is of importance for gas biology research, Drs. Yoshikawa and Naito took over and completed Dr. Hideo’s work. The first “General” section is composed of three classic review papers which provide the necessary introduction to gas biology. The first chapter, entitled “Roles of Stress-Inducible Carbon Monoxide in the Regulation of Liver Function,” was written by Dr. Makoto Suematsu, et al. (pages 1-5). As the liver is a gigantic resource of CO derived from heme degradation in vivo, constitutive and inducible CO has been suggested to regulate porto-sinusoidal vascular and biliary function. Interestingly, Dr. Suematsu mentioned that cystathionine b-synthase (CBS), a heme-containing enzyme, acts as a CO sensor. The enzyme CBS is also known to be an important synthesizer of H2S; therefore this chapter suggests cross-communication among the biological signaling gas system. Dr. Yoshihisa Urita et al. cover “Intraluminal Gas and Gastrointestinal Disease” (pages 6-14). Gases are produced while passing through the gastrointestinal tract, possibly causing abdominal symptoms, while gas is continuously removed by eructation, anal evacuation, absorption through the intestinal mucosa, and bacterial consumption. Impaired gas movement in the alimentary tract is more closely associated with abdominal symptoms than is liquid movement. Intestinal gas is often cited as a major cause of irritable bowel syndrome (IBS). The last chapter of this section covers “Therapeutic Medical Gas” (pages 15-23), providing background and clinical feasibility of various therapeutic medical gases, such as NO, CO, H2S, H2, xenon, helium, and ozone. This chapter includes a table that lists potential therapeutic medical gases and summarizes their chemistry or biological effects (page 16). Section two, entitled “Gas and Medical Application: I. CO,” starts with the chapter “Analysis of Breath CO and Application to Hemodynamic Monitoring,” which describes monitoring methods using exhaled CO and its physiological roles on alimentary tracts. Dr. Sawano developed accurate, non-invasive, continuous carboxyhemoglobin densitometry by expired gas analysis (pages 24-34). Application of this technique to low-dose carboxyhemoglobin dilution achieved minimally invasive * Correspondence: nakaoa@upmc.edu Departments of Surgery and Cardiothoracic Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA Nakao and Toyoda Medical Gas Research 2011, 1:25 http://www.medicalgasresearch.com/content/1/1/25 MEDICAL GAS RESEARCH

Do Patients With Irritable Bowel Syndrome Exhale More Hydrogen Than Healthy Subjects in Fasting State?

TO THE EDITOR: Irritable bowel syndrome (IBS) is a common disorder characterized by persistent or recurrent abdominal pain and discomfort with altered bowel habits. It affects approximately 10%-20% of the adult population, with typical symptoms like abdominal pain, constipation, diarrhea and bloating.1,2 Although IBS is not lethal, it can reduce quality of life and increase medical costs. While the cause of IBS is still unclear, visceral hypersensitivity, immune activation, enteric neuromuscular dysfunction and dysfunction of the brain-gut axis have been suggested.3-6 Small intestinal bacterial overgrowth (SIBO) has also been proposed as an etiologic factor in IBS, but the evidence is conflicting yet.7

Mechanisms underlying gut dysfunction in a murine model of chronic parasitic infection

Irritable bowel syndrome (IBS) is common in countries where chronic parasitic infestations are endemic. However, the relationship between parasitic infection and IBS is not clear. The aim of this study was to examine whether chronic parasitic infection is accompanied by gut dysfunction and whether the continued presence of the parasite is required for the maintenance of the dysfunction. We used chronic Trichuris muris infection in Th1-biased susceptible AKR mice to evaluate this relationship. AKR mice were infected with T. muris and were euthanized on various days postinfection (pi) to examine worm burden, muscle function, and immune and inflammatory responses. Mice were treated with the anthelmintic oxantel pamoate to assess the effect of eradication of infection on muscle function. Infection resulted in persistence of the parasite, elevated IFN-γ, and increased MPO activity evident at 45 days pi. This was accompanied by a reduction in muscle contractility and excitatory innervation. Whereas parasite eradication at 7 days pi normalized IFN-γ and muscle contractility, eradication at 28 days pi failed to normalize muscle contractility. Administration of dexamethasone after parasite eradication normalized all parameters. Anthelmintic treatment improved histology except for eosinophils, which were normalized by subsequent dexamethasone therapy. Persistent gut dysfunction is independent of the continued presence of the parasite and is maintained by inflammatory process that includes eosinophils. Thus data in this preclinical model suggest that parasitic infection could be a cause of IBS, and the lack of symptomatic improvement following eradication is insufficient evidence to refute a causal relationship between the infection and IBS.

Evaluating a Bacterial Hypothesis in IBS Using a Modification of Koch's Postulates: Part 1

It has recently been suggested that irritable bowel syndrome (IBS) symptoms are due partly to small intestinal bacterial overgrowth (SIBO). This "SIBO hypothesis" has led to the use of antibiotics to treat IBS. Koch's postulates have long been used to establish bacteria as a cause of diseases such as tuberculosis. Because SIBO is not a single organism, we use modified Koch's postulates to argue for antibiotics and an SIBO hypothesis in the pathophysiology of IBS. We show that there is evidence for SIBO, that it is culturable, that antibiotic elimination of the bacteria improves subjects clinically, and that when the bacteria return, the symptoms return. On the basis of proof of a bacterial cause of IBS, antibiotics may be a good choice of therapy.

Familial Aggregation of Irritable Bowel Syndrome: A Family Case–Control Study

Irritable bowel syndrome (IBS) clusters in families, but previous studies documented family history only from patients. We have shown that patient-relative agreement on IBS status is poor. Thus, we conducted a family case-control study with direct survey of symptoms from family members to better quantitate the aggregation of IBS in families. The aims of this study were to (i) compare the prevalence of IBS in case-relatives with control-relatives, and (ii) determine whether gender, relationship, predominant symptom, and environmental risk factors affect familial aggregation. Outpatients with IBS, matched controls, and their first-degree relatives completed a bowel symptom questionnaire. Percent of cases and controls with a family history were compared and odds ratios were computed using chi(2)-test; recurrence risks to relatives were computed using logistic regression and generalized estimating equations. Data were collected from 477 cases, 297 controls, 1,492 case-relatives, and 936 control-relatives. Probands had a median age of 50 and 78% were women. 50% of case and 27% of control families had at least another relative with IBS yielding an odds ratio of 2.75 (95% CI: 2.01-3.76, P<0.0001). When aggregation estimates were reevaluated stratifying by relative relationship or proband gender, generational and gender effects were not observed. Familial clustering by bowel habit was weakest for diarrhea, and strongest for alternating bowel habits. IBS aggregates strongly in families. The strength of the association does vary somewhat by relationship to proband, but the lack of association in spouses supports either a possible genetic etiology or a shared household environmental exposure as an underlying cause of IBS.

Electroacupuncture attenuates visceral hyperalgesia and inhibits the enhanced excitability of colon specific sensory neurons in a rat model of irritable bowel syndrome

The causes of irritable bowel syndrome remain elusive and there are few effective treatments for pain in this syndrome. Electroacupunture (EA) is used extensively for treatment of various painful conditions including chronic visceral hyperalgesia (CVH). However, mechanism of its analgesic effect remains unknown. This study was designed to investigate effect of EA on colon specific dorsal root ganglion (DRG) neurons in rats with CVH. CVH was induced by intracolonic injection of acetic acid (AA) in 10-day-old rats. Electromyography and patch clamp recordings were performed at age of 8-10 weeks. Colon DRG neurons were labelled by injection of DiI into the colon wall. EA was given at ST36 in both hindlimbs. As adults, neonatal AA-injected rats displayed an increased sensitivity to colorectal distension (CRD) and an enhanced excitability of colon DRG neurons. EA treatment for 40 min significantly attenuated the nociceptive responses to CRD in these rats; this attenuation was reversed by pretreatment with naloxone. EA treatment for 40 min per day for 5 days produced a prolonged analgesic effect and normalized the enhanced excitability of colon DRG neurons. Furthermore, in vitro application of [D-Ala(2), N-MePhe(4), Gly(5)-Ol] enkephalin (DAMGO) suppressed the enhanced excitability of colon neurons from rats with CVH. These findings suggest that EA produced-visceral analgesia, which might be mediated in a large part by endogenous opioids pathways, is associated with reversal of the enhanced excitability of colon DRG neurons in rats with CVH.

Gastrointestinal physiology and digestive disorders in sleep

The dynamic interplay of the digestive system and sleep is an excellent example of brain-body interaction. New advances in measuring techniques provide an opportunity to evaluate physiology that is dependent upon the sleep/wake state or circadian rhythm and potentially differentiate between normal and pathological conditions. Sleep-related changes in gastrointestinal physiology create vulnerabilities to digestive issues such as reflux, whereas disorders such as duodenal ulcers raise the importance of circadian variations in digestive system function. Advances in the area of normal sleep physiology have furthered our understanding of the underlying cause of irritable bowel syndrome, and the mechanisms by which sleep disruption may aggravate inflammatory bowel disease. Additionally, important early work has shown that the treatment of digestive disorders such as reflux can improve sleep quality just as the improvement in sleep may aid in the treatment of digestive disorders. For the clinician, these forward steps in our knowledge mark the start of an era in which understanding the effects of the sleep/wake state and circadian rhythms on gastrointestinal physiology promise to yield novel diagnostic and therapeutic opportunities.

Bacterial Overgrowth and Irritable Bowel Syndrome: Unifying Hypothesis or a Spurious Consequence of Proton Pump Inhibitors?

Some studies indicate that small intestinal bacterial overgrowth (SIBO), as measured by hydrogen breath tests (HBT), is more prevalent in patients with irritable bowel syndrome (IBS) vs. matched controls without IBS. Although the data are conflicting, this observation has led to the hypothesis that SIBO may be a primary cause of IBS. Yet, it remains unclear whether SIBO is truly fundamental to the pathophysiology of IBS, or is instead a mere epiphenomenon or bystander of something else altogether. We hypothesize that SIBO might be a byproduct of the disproportionate use of proton pump inhibitors (PPIs) in IBS, as follows: (1) IBS patients are more likely than controls to receive PPI therapy; (2) PPI therapy may promote varying forms of SIBO by eliminating gastric acid; and (3) existing studies linking SIBO to IBS have not adjusted for or excluded the use of PPI therapy. When linked together, these premises form the basis for a simple and testable hypothesis: the relationship between SIBO and IBS may be confounded by PPIs. Our article explores these premises, lays out the argument supporting this "PPI hypothesis," discusses potential implications, and outlines next steps to further investigate this possibility.