Bovine immunoglobulin protein isolates for the nutritional management of enteropathy

The gastrointestinal tract is responsible for a multitude of digestive and immune functions which depend upon the balanced interaction of the intestinal microbiota, diet, gut barrier function, and mucosal immune response. Disruptions in one or more of these factors can lead to intestinal disorders or enteropathies which are characterized by intestinal inflammation, increased gut permeability, and reduced capacity to absorb nutrients. Enteropathy is frequently associated with human immunodeficiency virus (HIV) infection, inflammatory bowel disease, autoimmune enteropathy, radiation enteritis, and irritable bowel syndrome (IBS), where pathologic changes in the intestinal tract lead to abdominal discomfort, bloating, abnormal bowel function (e.g., diarrhea, urgency, constipation and malabsorption). Unfortunately, effective therapies for the management of enteropathy and restoring intestinal health are still not available. An accumulating body of preclinical studies has demonstrated that oral administration of plasma- or serum-derived protein concentrates containing high levels of immunoglobulins can improve weight, normalize gut barrier function, and reduce the severity of enteropathy in animal models. Recent studies in humans, using serum-derived bovine immunoglobulin/protein isolate, demonstrate that such protein preparations are safe and improve symptoms, nutritional status, and various biomarkers associated with enteropathy. Benefits have been shown in patients with HIV infection or diarrhea-predominant IBS. This review summarizes preclinical and clinical studies with plasma/serum protein concentrates and describes the effects on host nutrition, intestinal function, and markers of intestinal inflammation. It supports the concept that immunoglobulin-containing protein preparations may offer a new strategy for restoring functional homeostasis in the intestinal tract of patients with enteropathy.     

Postpartum fecal incontinence is more common in women with irritable bowel syndrome

PURPOSE: Anal sphincter damage can occur during vaginal delivery and may lead to impairment of fecal continence. The aim of this study was to determine the influence of irritable bowel syndrome on symptoms of fecal incontinence following first vaginal delivery. METHODS: A prospective, observational study was performed before delivery, six weeks, and six months following delivery in primiparous women. A bowel function questionnaire was completed, and anal vector manometry, mucosal electrosensitivity, pudendal nerve terminal motor latency, and anal endosonography were performed. A total of 208 women were assessed before and after delivery, and 104 primigravid women were studied after delivery only. A total of 34 of 312 (11 percent) had an existing diagnosis of irritable bowel syndrome. RESULTS: The prevalence of abnormal manometry or endosonography was similar in women with and without irritable bowel syndrome. However, six weeks after delivery, women with irritable bowel syndrome had a higher incidence of defecatory urgency (64 percent) and loss of control of flatus (35 percent) compared with those without (urgency, 10 percent,P<0.001; flatus, 13 percent,P=0.007). The incidence of frank fecal incontinence was similar in the two groups. Women with IBS had increased mucosal sensitivity to electrical stimulation of the upper anal canal both before and after delivery. CONCLUSION: Women with IBS are more likely to experience subjective alteration of fecal continence postpartum compared with the healthy primigravid population, but they are not at increased risk of anal sphincter injury.     

Double-blind placebo-controlled study of mesalamine in post-infective irritable bowel syndrome - a pilot study

Abstract Objective. Post-infective irritable bowel syndrome (PI-IBS) is characterized by continuing symptoms of irritable bowel syndrome, typically diarrhea-predominant, following an episode of acute gastroenteritis. There is often an increase in sub-epithelial inflammatory and neuroendocrine cells on colonic mucosal biopsy. Mesalamine is an anti-inflammatory agent, effective in the treatment of inflammatory bowel disease. The goal of this study was to compare mesalamine to placebo on symptoms and quality-of-life (QOL) in PI-IBS. Material and methods. Twenty patients who developed diarrhea-predominant IBS after gastroenteritis were randomized to receive mesalamine (Asacol?) 1.6 gm b.i.d. or placebo for 12 weeks in a double-blind placebo-controlled study. QOL was assessed using the IBS-QOL questionnaire. Stool frequency, stool consistency, urgency, severity of abdominal pain, severity of bloating, and global-improvement scale were recorded in daily diaries for 7 days at baseline and every 4 weeks. Data were analyzed by comparing the change from baseline to last follow-up. Results. One patient withdrew after randomization; data were incomplete in two patients. Thus, data were analyzed from 17 patients (11 men and 6 women, median age: 27 years, range 22-45 years). Mesalamine was not associated with significant improvement in global symptoms, abdominal pain, bloating, stool urgency, frequency, or consistency (all p ≥ 0.11) or QOL (p ≥ 0.16). Conclusions. There was no significant improvement in global symptoms or overall QOL with mesalamine in patients with PI-IBS.     

复方谷氨酰胺肠溶胶囊对腹泻为主型肠易激综合征的临床疗效观察

肠易激综合征（IBS）是一种常见的慢性肠功能紊乱性疾病，目前治疗方法较多，但疗效均不确切。目的：观察复方芥氨酰胺肠溶胶囊对腹泻为主型IBS的临床疗效。方法：80例腹泻为主型IBS患者随机分为2组。每组40例，分别予复厅符氨酰胺肠溶胶囊（500mg，3次／天）和枯草杆菌、肠球菌二联活菌肠溶胶囊（500mg，3次／天），疗程2周。治疗7天和14天后询问并记录腹泻、腹痛和腹胀等症状的改善情况。结果：复方谷氨酰胺肠溶胶囊组的总有效率为85．0％，二联活菌肠溶胶囊组为72．5％，差异无统计学意义；复方谷氨酰胺肠溶胶囊治疗腹泻的疗效优于二联活菌肠溶胶囊（92．5％对60．0％，P〈0．05），两组对腹痛、腹胀的疗效无统计学差异．结论：复方谷氨酰胺肠溶胶囊和二联活菌肠溶胶囊均对腹泻为主型IBS有效，但前者治疗腹泻的疗效优于后者。     

Urgency and fecal soiling in people with bowel dysfunction

The frequency of urgency and fecal soiling in the population and among people with irritable bowel syndrome (IBS), and the association of these symptoms with health care seeking is unknown. Among 1128 students and hospital employees that we surveyed, urgency was reported in 14.4%, fecal soiling in 5.3%, and diarrhea in 9.0%. Most persons with fecal soiling did not report urgency or diarrhea. Although bowel dysfunction compatible with IBS was present in 20% (227), only 29% of this group (65) had seen a physician for bowel complaints. People with bowel dysfunction were more likely to be women, to take laxatives, and to have rectal urgency. Fecal soiling was more likely among those with bowel dysfunction who had been to the doctor, and included almost half of the men in this group. There was no difference in the frequency of diarrhea reported among those with bowel dysfunction regardless of whether they had been to the doctor. These data suggest fecal soiling may influence people with bowel dysfunction to go to the doctor. Physiological studies are needed to determine if anal sphincter dysfunction is a component of IBS.     

Functional outcome after restorative proctocolectomy

Incontinence and pouchitis are complications that affect most patients who have undergone restorative proctocolectomy. Incontinence, with particular regard to night leakage, is related to the combination of poorly functioning ileal reservoir and poor anal sphincter function. Pouchitis, the major late complication of restorative proctocolectomy, is quite similar to the previous inflammatory bowel disease. Pouchitis has an important impact on functional results after restorative proctocolectomy, causing a significant increase in defecation frequency, pain on evacuation, urgency, watery bowel movements, bloody diarrhea, anal irritation and stool leakage. In particular, chronic pouchitis can cause distress, anxiety and disappointment for patients needing continuous treatment. The influence of anal sphincter and ileal pouch function on clinical outcome after ileal pouch-anal anastomosis (IPAA) is reviewed, together with the correlation between ileal pouch function and pouchitis. The possible correlation between pouchitis and long-term functional outcome after restorative proctocolectomy is examined. Received: 28 May 1998 / Accepted in revised form: 22 September 1999     

Eradication of small intestinal bacterial overgrowth reduces symptoms of irritable bowel syndrome

OBJECTIVES: Irritable bowel syndrome is the most common gastrointestinal diagnosis. The symptoms of irritable bowel syndrome are similar to those of small intestinal bacterial overgrowth. The purpose of this study was to test whether overgrowth is associated with irritable bowel syndrome and whether treatment of overgrowth reduces their intestinal complaints. METHODS: Two hundred two subjects in a prospective database of subjects referred from the community undergoing a lactulose hydrogen breath test for assessment of overgrowth were Rome I criteria positive for irritable bowel syndrome. They were treated with open label antibiotics after positive breath test. Subjects returning for follow-up breath test to confirm eradication of overgrowth were also assessed. Subjects with inflammatory bowel disease, abdominal surgery, or subjects demonstrating rapid transit were excluded. Baseline and after treatment symptoms were rated on visual analog scales for bloating, diarrhea, abdominal pain, defecation relief, mucous, sensation of incomplete evacuation, straining, and urgency. Subjects were blinded to their breath test results until completion of the questionnaire. RESULTS: Of 202 irritable bowel syndrome patients, 157 (78%) had overgrowth. Of these, 47 had follow-up testing. Twenty-five of 47 follow-up subjects had eradication of small intestinal bacterial overgrowth. Comparison of those that eradicated to those that failed to eradicate revealed an improvement in irritable bowel syndrome symptoms with diarrhea and abdominal pain being statistically significant after Bonferroni correction (p < 0.05). Furthermore, 48% of eradicated subjects no longer met Rome criteria (chi2 = 12.0, p < 0.001). No difference was seen if eradication was not successful. CONCLUSIONS: Small intestinal bacterial overgrowth is associated with irritable bowel syndrome. Eradication of the overgrowth eliminates irritable bowel syndrome by study criteria in 48% of subjects.     

A randomized,double-blind,placebo-controlled clinical trial of the effectiveness of the novel serotonin type 3 receptor antagonist ramosetron in both male and female Japanese patients with diarrhea-predominant irritable bowel syndrome

Objective. Irritable bowel syndrome is characterized by abdominal discomfort and/or pain associated with altered bowel habits. The neurotransmitter serotonin and serotonin type 3 receptors that are extensively distributed on enteric neurons in the human gastrointestinal tract play a role in increasing the sensation of pain and affecting bowel habits in patients with irritable bowel syndrome. The aim of this study was to evaluate the efficacy and safety of the serotonin type 3 receptor antagonist ramosetron hydrochloride in Japanese patients with diarrhea-predominant irritable bowel syndrome. Material and methods. In a double-blind, placebo-controlled, parallel group-comparative study with a 1-week run-in period, 539 patients with diarrhea-predominant irritable bowel syndrome meeting the Rome II diagnostic criteria received either 5 µg ramosetron hydrochloride (n=270) or placebo (n=269) once daily for 12 weeks. Results. Forty-seven percent of ramosetron hydrochloride-treated patients were monthly responders in the primary end-point, “Patient-reported global assessment of relief of irritable bowel syndrome symptoms”, compared with 27% for placebos (p<0.001). The most frequently reported adverse event in the ramosetron hydrochloride-treated group compared with the placebo group was hard stool. Conclusions. Ramosetron hydrochloride 5 µg once daily is effective and well tolerated in the treatment of abdominal pain, discomfort and bowel habits in patients with diarrhea-predominant irritable bowel syndrome.     

益生菌制剂在消化系统中的应用

益生菌制剂可以恢复肠道菌群平衡和黏膜屏障功能,从而治疗相关疾病,其安全性和有效性已在临床上得到验证。现就近年来益生菌制剂在抗生素相关性腹泻、溃疡性结肠炎、腹泻型肠易激综合征、功能性便秘和慢性肝病等常见消化道疾病中的临床应用作一概述,为更好地开发和医用益生菌制剂奠定基础。     

便秘型和腹泻型肠易激综合征患者肛门直肠运动及直肠感觉功能的检测分析

目的研究便秘型和腹泻型肠易激综合征(IBS)患者肛门直肠运动及直肠感觉改变。方法对2000-01~2004-01广州医学院第二附属医院根据罗马Ⅱ标准入选的便秘型IBS30例,腹泻型IBS20例,正常对照组26例,进行肛门直肠运动功能及直肠感觉测定。结果(1)便秘型和腹泻型IBS肛门括约肌压力、肛门括约肌最大缩窄压和正常对照组相比差异无显著性(P>0.05);增加腹压时,肛门括约肌净增压腹泻型低于正常对照组(P<0.05);模拟大便时直肠和肛门括约肌出现同步收缩发生率便秘型IBS高于正常对照组(P<0.01)。(2)便秘型IBS直肠对容量刺激的最低敏感量、最大耐受性、顺应性明显高于正常对照组(P<0.01)。(3)腹泻型IBS直肠对容量刺激的最低敏感量、最大耐受性、顺应性明显低于正常对照组(P<0.01)。结论(1)IBS存在肛门直肠运动异常。(2)便秘型IBS直肠对容量刺激低敏感、高耐受、高顺应性,可能是引起便秘原因之一。(3)腹泻型IBS直肠对容量刺激存在高敏感、低耐受、低顺应性和肛门自控能力减弱,可能与腹泻有关。     

Mechanisms of Diarrhea

Diarrhea is a symptom common to a wide variety of gastrointestinal illnesses, and is an important public health challenge in underdeveloped regions of the world. Normal intestinal absorption is a complex process. Recent research offers new insights into normal physiology and pathophysiology. The role of the enteric nervous system and neurotransmitters in the pathogenesis of diarrhea in inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) is being actively investigated. In patients with IBD, ileal and sigmoid biopsies showed altered transepithelial sodium and fluid transport, specifically from decreased expression of the NHE3, NHERF-1, and NHE1 epithelial Na channel. This results in changes in normal intestinal electroneutral NaCl absorption and may be an additional factor contributing to the diarrhea in patients with IBD. Physiologic studies in humans suggest that primary bile acid malabsorption may be caused by an abnormal feedback system resulting in the increased bile salts, which may explain the watery diarrhea. Finally, the role of zinc in treatment of infectious diarrhea led to studies of its effect on intracellular human enterocyte ion secretion. Understanding such basic mechanisms may lead to better and novel therapies for treatment of diarrhea.     

Intestinal epithelial barrier and neuromuscular compartment in health and disease

A number of digestive and extra-digestive disorders, including inflammatory bowel diseases, irritable bowel syndrome, intestinal infections, metabolic syndrome and neuropsychiatric disorders, share a set of clinical features at gastrointestinal level, such as infrequent bowel movements, abdominal distension, constipation and secretory dysfunctions. Several lines of evidence indicate that morphological and molecular changes in intestinal epithelial barrier and enteric neuromuscular compartment contribute to alterations of both bowel motor and secretory functions in digestive and extra-digestive diseases. The present review has been conceived to provide a comprehensive and critical overview of the available knowledge on the morphological and molecular changes occurring in intestinal epithelial barrier and enteric neuromuscular compartment in both digestive and extra-digestive diseases. In addition, our intent was to highlight whether these morphological and molecular alterations could represent a common path(or share some common features) driving the pathophysiology of bowel motor dysfunctions and related symptoms associated with digestive and extra-digestive disorders. This assessment might help to identify novel targets of potential usefulness to develop original pharmacological approaches for the therapeutic management of such disturbances.     

Probiotics in gastroenterology

Probiotics are defined as live microorganisms of human origin. Their use may favorably influence human health and ameliorate or prevent certain diseases. Prebiotics are non-digestible foodstuffs (fiber, oligofructans - "colonic foods"), which enter the colon and are metabolized by the probiotics. Probiotics should fulfill the following criteria: Phenotypic and genotypic classification, no pathogenic properties, human origin, application in the living state, resistance to gastric acid and bile, ability to adhere to colonocytes, ability to colonize the gut, clinically proved favorable health-effect, and safety. Experimental and clinical studies supplied evidence of the possible use of probiotics in the following diseases: Traveler's diarrhea, antibiotic-associated diarrhea, relapsing Clostridium difficile colitis, infantile diarrhea, rotavirus enteritis, inflammatory bowel disease, irritable bowel syndrome, colon cancer, peritonitis, acute pancreatitis, and diarrhea associated with HIV infection. Probiotics displayed the following effects in these studies: Involvement in production of essential nutrients of the colonic mucosa, beneficial effect on intestinal immunity, recovery of the disturbed gut mucosal barrier and prevention of microbial translocation, elimination of toxins and eradication of microbial pathogens, production of steroids from cholesterol and reduction of its pool in circulation, participation in regulation of intestinal functions, reduced incidence of chemically induced colon tumors in rodents. Probiotics open new therapeutic modalities in a number of diseases and it may be expected that their importance will increase with growing knowledge and experience.     

感染后肠易激综合征研究现状

肠易激综合征（IBS）是最常见的功能性胃肠病之一,已有研究证据表明其可能是多种因素共同作用的结果,包括遗传和环境因素、胃肠动力改变、内脏高敏感、肠道感染和炎症、慢性应激、肠道细菌过度生长和脑-肠轴功能紊乱等。部分患者在急性肠道感染恢复后仍存在腹痛、腹部不适、腹泻等症状,即感染后肠易激综合征（PI-IBS）,是近年功能性胃肠病的研究热点。本文就PI-IBS的定义、流行病学、发病机制、动物模型、临床特征、诊断和治疗等研究现状作一概述。     

A case of systemic lupus erythematosus presenting with intestinal lymphangiectasia-associated protein-losing enteropathy accompanying hyperinflammation

Systemic lupus erythematosus (SLE) has the potential to affect virtually every organ; however, gastrointestinal system manifestations are relatively rare compared to other autoimmune diseases such as systemic sclerosis and inflammatory bowel disease. A 29-year-old female patient attended to the emergency room with abdominal distention, acute onset abdominal pain and constipation. She had watery chronic diarrhea (4-5 times/d) and weight loss (6 kg, 12%) for 4 months. While there was increased intestinal wall thickness, air-liquid levels were shown on abdomen computed tomography scan. The patient underwent abdominal surgery due to diagnosis of ileus. Ileocecal resection was performed and pathologic evaluation revealed intestinal lymphangiectasia. Autoimmune serology was performed with the following resulats: anti-nuclear antibody 1/3200 with homogenous pattern, anti-DNA antibody and anti-Sm/ribonucleoprotein antibodies were positive in addition to low complement levels (C3: 0.28 [0.9-1.8 g/L], C4: 0.06 [0.1-0.4 g/L]) indicating diagnosis of SLE. Development of intestinal involvement in SLE (lupus enteritis) is mainly grouped into 3 headings such as mesenteric vasculitis, pseudo-obstruction, and protein-losing enteropathy. Although the pathogenesis of intestinal lymphangiectasia remains unknown, it has been reported that immune complex-mediated visceral vasculitis may result in bowel wall and mucosal edema. To our knowledge this is the first case report accompanying hyperinflammatory response in addition to intestinal lymphangiectasia in SLE. On the other hand, clinicians should be alert for other reasons for hyperinflammatory syndromes rather than COVID-19, even during the pandemic.     

Enteric and central contributions to intestinal dysmotility in irritable bowel syndrome

The aim of the study was to further elucidate the pathophysiology of irritable bowel syndrome and its subgroups by examining and comparing alterations in small bowel motility, specifically phase II and phase III components of the migrating motor complex. Prolonged recordings of interdigestive small bowel motility were obtained during both diurnal and nocturnal periods in 20 patients with irritable bowel syndrome--10 with predominant constipation and 10 with predominant diarrhea--and in 10 healthy subjects. Diurnal amplitude (mean +/- SD) of phase III activity fronts was lower (P less than 0.05) in constipation-predominant patients (16.3 +/- 3.1 mm Hg) than in diarrhea-predominant patients (20.2 +/- 3.1) or controls (20.9 +/- 2.7). Similar findings were observed nocturnally. Phase III cycle length was also significantly prolonged diurnally in constipation-predominant patients when compared to the other groups. In the diarrhea-predominant group repetitive and rapidly propagated bursts of contractions were observed in eight patients, and this pattern occupied a significantly greater proportion of phase II motor activity than in controls. These alterations in phase II and in phase III components of the migrating motor complex suggest that both local (enteric) and more central mechanisms may operate to produce intestinal dysmotility in the irritable bowel syndrome and that these mechanisms differ according to the predominant alteration of bowel habit.     

Pericrypt eosinophilic enterocolitis and chronic diarrhea.

An unusual pattern of eosinophilic infiltration around intestinal crypts was detected in mucosal biopsy specimens of 10 patients with chronic diarrhea, half of whom had evidence of systemic connective tissue disease. The median duration of symptoms was 11 months, and no other explanation for diarrhea could be determined in any case. The cellular infiltrate on biopsy specimens was present deep in the mucosa of small and large intestinal specimens, separating crypt bases from the muscularis mucosae and penetrating the latter. Consistent with the microscopic findings, surface mucosal appearance by endoscopy was uniformly normal. These histological features of colonic biopsy specimens were statistically differentiated from those of asymptomatic subjects (n = 8), subjects with diarrhea-predominant irritable bowel syndrome (n = 6), and subjects with collagenous colitis (n = 7) or lymphocytic colitis (n = 5). Diarrhea improved in five of seven subjects treated with oral prednisone or prednisone in conjunction with azathioprine (median follow-up period, 2.2 years). Histological changes on subsequent biopsy specimens correlated closely with symptomatic status. These findings strongly suggest that chronic diarrhea is related to this pericrypt eosinophilic enterocolitis, a pathological lesion often associated with features of systemic connective tissue disease. The disorder appears responsive to corticosteroid therapy in some cases.     

Cellular and molecular basis of intestinal barrier dysfunction in the irritable bowel syndrome

The etiopathogenesis of the irritable bowel syndrome (IBS), one of the most prevalent gastrointestinal disorders, is not well known. The most accepted hypothesis is that IBS is the result of the disturbance of the 'brain-gut axis.' Although the pathophysiological mechanisms of intestinal dysfunction are complex and not completely understood, stress, infections, gut flora, and altered immune response are thought to play a role in IBS development. The intestinal barrier, composed of a single-cell layer, forms a physical barrier that separates the intestinal lumen from the internal milieu. The loss of integrity of this barrier is related with mucosal immune activation and intestinal dysfunction in IBS. The number of mast cells and T lymphocytes is increased in the intestinal mucosa of certain IBS patients, and the mediators released by these cells could compromise the epithelial barrier function and alter nerve signaling within the enteric nervous system. The association of clinical symptoms to structural and functional abnormalities of the mucosal barrier in IBS patients highlights the importance of understanding the physiological role of the gut barrier in the pathogenesis of this disorder. This review summarizes the clinical and experimental evidences indicating the cellular and molecular mechanisms of IBS symptomatology, and its relevance for future translational research.     

Elevated Vasoactive Intestinal Peptide Concentrations in Patients with Irritable Bowel Syndrome

The aim was to assess the roles of gut hormones and immune dysfunction in irritable bowel. In Study I, rectal mucosal samples examined blindly showed no histological evidence of inflammation in 16 irritable bowel patients compared to 17 healthy controls. The proinflammatory mediators interleukin-1beta and prostaglandin E2 also failed to show evidence of inflammation. Vasoactive intestinal peptide was elevated in irritable bowel (P = 0.01), but substance P, calcitonin gene-related peptide, and somatostatin levels were similar to control values. In Study II, 30 irritable bowel patients had elevated (P = 0.002) plasma concentrations of vasoactive intestinal peptide compared to 30 controls, and peptide levels were unrelated to whether the patient's predominant bowel habit was constipation, diarrhea, or both in alternation. In conclusion, no evidence of inflammation was detected in irritable bowel patients, but elevated vasoactive intestinal peptide concentrations were observed in both studies and might represent a potential diagnostic tool for irritable bowel syndrome.