Epidemiological and clinical perspectives on irritable bowel syndrome in India,Bangladesh and Malaysia: A review

Irritable bowel syndrome(IBS) is a chronic gastrointestinal disorder, common in clinic and in the community. It has a significant impact on both society and patients' quality of life. The epidemiology, clinical presentation, and management of IBS may vary in different geographical regions due to differences in diet, gastrointestinal infection, socio-cultural and psychosocial factors, religious and illness beliefs, symptom perception and reporting. Although previous reviews and consensus reports on IBS in Asia have been published, Asia is quite diverse socio-demographically. In this context, India, Bangladesh and Malaysia share some similarities, including:(1) large proportion of the population living in rural areas;(2) rapid development and associated lifestyle changes in urban areas; and(3) dietary, cultural and religious practices. The present review explores the clinical and epidemiological data on IBS from these three major nations in South and South-East Asia. In-depth review of the literature revealed important differences between IBS in the East, as revealed by studies from these three countries, and the West; these include a predominantly rural profile, differences in bowel habit and symptom profile, raising concern with regards to diagnostic criteria and subtyping of IBS, higher dietary fiber consumption, frequent lactose malabsorption, parasitosis, and possible overlap between post-infectious IBS and tropical sprue. Moreover, the current perception on difference in prevalence of the disorder in these countries, as compared to the West, might be related to variation in survey methods.     

Epidemiology of irritable bowel syndrome in Asia: Something old, something new, something borrowed

In this review we have unearthed epidemiological data that; support the 'old' concept of irritable bowel syndrome (IBS) as a disorder of civilization, build a 'new' symptom profile of IBS for Asia, and persuade us against the use of 'borrowed' Western diagnostic criteria and illness models by Asian societies. In the 1960s, IBS was described as a disorder of civilization. Early studies from Asia suggested a prevalence of IBS below 5%. Recent studies from Asia suggest a trend for the more affluent city states like Singapore and Tokyo, to have higher prevalence of 8.6% and 9.8%, respectively, while India had the lowest prevalence of 4.2%. Furthermore, there was a trend among the better educated and more affluent strata of society in several urban Chinese populations for a higher prevalence of IBS, as well as a trend for a higher consultation rate. Across Chinese and Indian predominant populations, a majority of patients with IBS criteria report upper abdominal symptoms such as epigastric pain relieved by defecation, bloating and dyspepsia. Bloating and incomplete evacuation appear to be more important determinants of consultation behavior, than psychological factors. The failure of the Rome criteria to recognize the relationship to meals, may have led to a substantial misclassification of IBS as dyspepsia. The relevance of the Western model of psychological disturbance as a determinant of consultation behavior is questionable because of the accessibility and acceptability of medical consultation for gastrointestinal complaints in many Asian communities.     

Gender, age, society, culture, and the patient's perspective in the functional gastrointestinal disorders

Patients with functional gastrointestinal disorders (FGID) often experience emotional distress, a perceived lack of validation, and an unsatisfactory experience with health care providers. A health care provider can provide the patient with a framework in which to understand and legitimize their symptoms, remove self-doubt or blame, and identify factors that contribute to symptoms that the patient can influence or control. This framework can be strengthened with the consideration of various important factors that impact FGID but are often overlooked. These include gender, age, society, culture, and the patient's perspective. There is evidence for sex- and gender-related differences in FGID, particularly irritable bowel syndrome (IBS). Whereas the majority of FGID, including IBS, bloating, constipation, chronic functional abdominal pain, and pelvic floor dysfunction, are more prevalent in women than men, functional esophageal and gastroduodenal disorders do not appear to vary by gender. Limited studies suggest that sex differences in visceral perception, cardioautonomic responses, gastrointestinal motility, and brain activation patterns to visceral stimuli exist in IBS. Gender differences in social factors, psychological symptoms, and response to psychological treatments have not been adequately studied. However, there appears to be a greater clinical response to serotonergic agents developed for IBS in women compared to men. The impact of social and cultural factors on the meaning, expression, and course of FGID are important. The prevalence of IBS appears to be lower in non-Western than Western countries. Although further studies are needed, the existing literature suggests that they are important to consider from both research and clinical perspectives.     

Irritable bowel syndrome: Epidemiology,diagnosis and treatment: An update for health‐care practitioners

Irritable bowel syndrome (IBS), a chronic gastrointestinal disorder, affects from 3–20% of the US population, depending on sociocultural and comorbid factors. IBS is characterized by a symptom complex of abdominal pain and abnormal bowel habits that present as diarrhea or constipation, and general physical weakness in the absence of abnormal morphological, histological or inflammatory markers. The main diagnostic Rome III criteria as established by international professional organizations are based on exclusion criteria and the occurrence and rate of symptoms. Because the pathophysiology and causes of IBS are poorly understood, treatment approaches are mainly focused on symptom management to maintain everyday functioning and improve quality of life for persons with IBS. The mainstay of intervention is pharmacological treatment with antispasmodics and antidiarrheals for diarrhea, prokinetics and high‐fiber diets for constipation, and supportive therapy with low‐dose antidepressants to normalize gastrointestinal motility. Other interventions include lifestyle and dietary changes, psychotherapy, herbal therapies and acupuncture. The purpose of this review is to critically assess benefits and risks of current treatment approaches as well as promising complementary and alternative therapies.     

Modulation of Sleep Quality and Autonomic Functioning by Symptoms of Depression in Women with Irritable Bowel Syndrome

The objective of this study was to determine how depressive symptoms affect autonomic activity during sleep, objective and subjective sleep, and gastrointestinal symptom severity in women with irritable bowel syndrome (IBS). Seventy women who met the Rome II criteria for IBS and 21 healthy volunteers participated. All participants were recruited from the surrounding community. IBS patients were stratified into two groups based on their Beck Depression Inventory II score and 44 IBS patients with depressive symptoms (IBS+DS) were compared to 26 IBS patients without depressive symptoms (IBS-DS). Autonomic activity was measured by heart rate variability (HRV) analysis. Fifteen-minute segments were selected from a baseline presleep period, stage 2, slow-wave sleep, and rapid-eye movement sleep for heart rate variability spectral analysis. Subjective sleep quality was assessed by the Pittsburg Sleep Quality Index (PSQI) and gastrointestinal symptom severity was assessed by an 18-item questionnaire. The IBS+DS group reported significantly (P < 0.01) more sleep complaints, measured by the PSQI, than the IBS-DS group and healthy controls. The IBS+DS group took significantly (P < 0.05) longer to enter their first rapid-eye movement period than healthy controls. The IBS+DS group reported significantly (P = 0.01) increased gastrointestinal symptom severity compared to the IBS-DS group. There were no significant group differences in autonomic activity during the baseline presleep period or sleep stages. The results demonstrated that IBS patients with significant depressive symptoms had increased gastrointestinal symptom severity, increased sleep complaints, and alterations in sleep architecture compared to healthy controls and IBS patients without significant depressive symptoms.     

Asian consensus on irritable bowel syndrome

Background and Aims: Many of the ideas on irritable bowel syndrome (IBS) are derived from studies conducted in Western societies. Their relevance to Asian societies has not been critically examined. Our objectives were to bring to attention important data from Asian studies, articulate the experience and views of our Asian experts, and provide a relevant guide on this poorly understood condition for doctors and scientists working in Asia. Methods: A multinational group of physicians from Asia with special interest in IBS raised statements on IBS pertaining to symptoms, diagnosis, epidemiology, infection, pathophysiology, motility, management, and diet. A modified Delphi approach was employed to present and grade the quality of evidence, and determine the level of agreement. Results: We observed that bloating and symptoms associated with meals were prominent complaints among our IBS patients. In the majority of our countries, we did not observe a female predominance. In some Asian populations, the intestinal transit times in healthy and IBS patients appear to be faster than those reported in the West. High consultation rates were observed, particularly in the more affluent countries. There was only weak evidence to support the perception that psychological distress determines health‐care seeking. Dietary factors, in particular, chili consumption and the high prevalence of lactose malabsorption, were perceived to be aggravating factors, but the evidence was weak. Conclusions: This detailed compilation of studies from different parts of Asia, draws attention to Asian patients' experiences of IBS.     

Relationship between severity of symptoms and quality of life in 858 patients with irritable bowel syndrome

AIMS: Heath-related quality of life (QoL) is decreased in patients with irritable bowel syndrome (IBS) but the relationship between symptom intensity of IBS and QoL remains largely unknown. The aim of this prospective survey was to investigate the relationship between intensity of IBS and changes in QoL. METHODS: Eight hundred and fifty-eight patients with IBS, according to Rome II criteria, completed a symptom questionnaire to measure intensity of IBS, and the gastrointestinal quality of life (GIQLI) questionnaire, which is a general QoL measure in patients with gastrointestinal disorders. RESULTS: 37.2% of the patients had constipation-predominant type IBS, 37.3% had diarrhea-predominant IBS and 25.4% had alternating diarrhea and constipation type symptoms. IBS was considered to be in remission or mild in 8.3% of patients; 41.3% had moderate IBS and 50.4% had severe IBS. The mean GIQLI score was 88 +/- 20. There was a significant correlation between symptom intensity and changes in QoL. Other significantly related factors were the type of bowel abnormality and gender. CONCLUSION: In IBS patients, symptom intensity and type of IBS have a negative impact on health-related QoL.     

Irritable bowel syndrome: Bacterial overgrowth—What’s known and what to do

Opinion statement Irritable bowel syndrome (IBS) is a common gastrointestinal condition whose cause remains unknown. Therefore, most of our effort in treating IBS has been based on a symptom approach. Recent evidence is beginning to suggest that subjects with IBS may have an alteration in gastrointestinal flora. Specifically, findings suggest that IBS patients have excessive bacteria in the small bowel, known as bacterial overgrowth. Although diagnostic testing for bacterial overgrowth is somewhat controversial, as there is no true gold standard test for bacterial overgrowth, antibiotic-based therapies for IBS are now shown to be very effective in treating IBS. Follow-up work in this area has even begun to demonstrate associative factors between gut bacteria and IBS that may explain the different types of IBS. The best example of this is the finding that methanogenic organisms in IBS patients are wholly associated with constipation-predominant IBS. It seems that the methane gas emitted during fermentation may have an influence on gut motility. In this review, the evidence for gut ecology associations in IBS is presented. A treatment algorithm also is proposed based on these findings. New areas of research in IBS such as gut bacteria are changing the treatment approach in IBS from a symptom-based style to one that is hypothesis driven.     

Pathogenic factors involved in the development of irritable bowel syndrome: focus on a microbial role

Irritable bowel syndrome (IBS) is a symptom complex characterized by recurrent abdominal pain or discomfort, and accompanied by abnormal bowel habits, in the absence of any discernible organic abnormality. Its origin remains unclear, partly because multiple pathophysiologic mechanisms are likely to be involved. A significant proportion of patients develop IBS symptoms after an episode of gastrointestinal infection. In addition to gastrointestinal pathogens, recent evidence suggests that patients with IBS have abnormal composition and higher temporal instability of their intestinal microbiota. Because the intestinal microbiota is an important determinant of normal gut function and immunity, this instability may constitute an additional mechanism that leads to symptom generation and IBS. More importantly, a role for altered microbiota composition in IBS raises the possibility of therapeutic interventions through selective antibiotic or probiotic administration. The new concept of functional bowel diseases incorporates the bidirectional communication between the gut and the central nervous system (gut-brain axis), which may explain the multiple facets of IBS by linking emotional and cognitive centers of the brain with peripheral functioning of the gastrointestinal tract and vice versa.     

Prevalence of irritable bowel syndrome and its relationship with psychological stress status in Chinese university students

Background and Aims: Although irritable bowel syndrome (IBS) is a common disorder in the West, information on the prevalence of IBS in university students is relatively scant, especially in Asia. The aims of the present study were to investigate the prevalence and pattern of symptoms of IBS and its relationship with psychological stress status in Chinese university students. Methods: Basic demographic data and IBS symptoms were sought using the Rome II criteria and a validated bowel symptom questionnaire. Another questionnaire used related to psychosomatic symptoms of depression and anxiety. Results: In total, 491 of the 530 students in the trial met the selected criteria, which included 241 men. The participants were medical college students (313/491) and non‐medical college students (178/491). The apparent prevalence of IBS was 15.7%, with a prevalence of 14.5% in men and 16.8% in women. The most common symptom was abdominal pain associated with change in the consistency of stool (36.9%), followed by altered stool frequency (16.3%), and abdominal pain relieved by defecation (12.4%), predominantly in women. The self‐reported psychological and psychosomatic symptoms of anxiety (P < 0.001) and depression (P < 0.001) were encountered more frequently in participants with IBS. The depression (P = 0.03) and anxiety measures (P = 0.02) significantly predicted IBS status. Conclusion: The prevalence of IBS in Chinese university students is often compared with university students in developed countries and the general Chinese population. Depression and anxiety could potentially induce IBS. Medical education should be considered when aiming to reduce stress of university students who are susceptible to IBS.     

Aspects of the non-pharmacological treatment of irritable bowel syndrome

Irritable bowel syndrome (IBS) is one of the most commonly diagnosed gastrointestinal conditions. It represents a significant healthcare burden and remains a clinical challenge. Over the years IBS has been described from a variety of different perspectives; from a strict illness of the gastrointestinal tract (medical model) to a more complex multi-symptomatic disorder of the brain-gut axis (biopsychosocial/psychosomatic model). In this article we present aspects of the pathophysiology and the non-pharmacological treatment of IBS based on current knowledge. Effects of conditioned stress and/or traumatic influences on the emotional system (top-down) as well as effects on the intestine through stressors, infection, inflammation, food and dysbiosis (bottom-up) can affect brain-gut communication and result in dysregulation of the autonomic nervous system (ANS), playing an important role in the pathophysiology of IBS. Conditioned stress together with dysregulation of the autonomic nervous system and the emotional system may involve reactions in which the distress inside the body is not recognized due to low body awareness. This may explain why patients have difficulty identifying their symptoms despite dysfunction in muscle tension, movement patterns, and posture and biochemical functions in addition to gastrointestinal symptoms. IBS shares many features with other idiopathic conditions, such as fibromyalgia, chronic fatigue syndrome and somatoform disorders. The key to effective treatment is a thorough examination, including a gastroenterological examination to exclude other diseases along with an assessment of body awareness by a body-mind therapist. The literature suggests that early interdisciplinary diagnostic co-operation between gastroenterologists and body-mind therapists is necessary. Re-establishing balance in the ANS is an important component of IBS treatment. This article discusses the current knowledge of body-mind treatment, addressing the topic from a practical point of view.     

Irritable bowel syndrome: recent developments in diagnosis,pathophysiology, and treatment

The diagnosis of irritable bowel syndrome (IBS) remains a diagnosis of exclusion, whereby an extensive investigation is performed to exclude other organic diseases that may explain the symptoms of patients. Attempts to have a positive diagnosis based on symptom assessments failed to achieve widely use in clinical practice. Abnormalities in the gastrointestinal endocrine cells in IBS patients have been reported recently, providing evidence that IBS is an organic disorder, and opening the door to the use of these abnormalities as markers for a positive diagnosis of IBS. New and promising drugs for the treatment of IBS with constipation as the predominant symptom are currently on the market, and the treatment results have been satisfactory thus far.     

Symptom Provocation in Irritable Bowel Syndrome Effects of Differing Doses of Fructose-Sorbitol

The role of fructose and sorbitol, when ingested together, in the aetiology of irritable bowel syndrome (IBS) is controversial. The aims of this study in IBS patients, therefore, were to compare differences in symptom provocation with various doses of fructose-sorbitol and to relate differences in the extent of colonic hydrogen production after each dose to such symptom provocation. Two different mixtures of fructose and sorbitol-20 g fructose plus 3.5 g sorbitol ('lower' dose) and 25 g fructose plus 5 g sorbitol (‘higher’ dose)-were administered to 15 patients with IBS and to 24 healthy controls. Breath hydrogen concentrations were determined at 10-min intervals for 3 h after ingestion of each mixture, and the presence and severity of a range of gastrointestinal symptoms were recorded on a standard form before, during, and after the study. Total symptom score in IBS patients, but not controls, was greater (p > 0.05) after the higher than after the lower dose of fructose-sorbitol mixture, and, for the higher dose, symptoms were significantly greater in IBS patients than in controls (p > 0.05). Moreover, the increase in total symptom score between the higher and lower dose mixtures was of a greater magnitude (p = 0.01) in IBS patients than in controls. No significant correlation was observed between the increase in symptom score and the increase in peak hydrogen concentration or the increase in integrated hydrogen response between lower and higher dose mixtures, although these latter increases were at times substantial. We conclude that in patients with IBS who ingest fructose and sorbitol simultaneously, the degree of symptom provocation is related to the amounts present in such a mixture but is not related directly to the extent of colonic hydrogen production.     

Manipulation of dietary short chain carbohydrates alters the pattern of gas production and genesis of symptoms in irritable bowel syndrome

Background and Aim: Reduction of short‐chain poorly absorbed carbohydrates (FODMAPs) in the diet reduces symptoms of irritable bowel syndrome (IBS). In the present study, we aimed to compare the patterns of breath hydrogen and methane and symptoms produced in response to diets that differed only in FODMAP content. Methods: Fifteen healthy subjects and 15 with IBS (Rome III criteria) undertook a single‐blind, crossover intervention trial involving consuming provided diets that were either low (9 g/day) or high (50 g/day) in FODMAPs for 2 days. Food and gastrointestinal symptom diaries were kept and breath samples collected hourly over 14 h on day 2 of each diet. Results: Higher levels of breath hydrogen were produced over the entire day with the high FODMAP diet for healthy volunteers (181 ± 77 ppm.14 h vs 43 ± 18; mean ± SD P < 0.0001) and patients with IBS (242 ± 79 vs 62 ± 23; P < 0.0001), who had higher levels during each dietary period than the controls (P < 0.05). Breath methane, produced by 10 subjects within each group, was reduced with the high FODMAP intake in healthy subjects (47 ± 29 vs 109 ± 77; P = 0.043), but was not different in patients with IBS (126 ± 153 vs 86 ± 72). Gastrointestinal symptoms and lethargy were significantly induced by the high FODMAP diet in patients with IBS, while only increased flatus production was reported by healthy volunteers. Conclusions: Dietary FODMAPs induce prolonged hydrogen production in the intestine that is greater in IBS, influence the amount of methane produced, and induce gastrointestinal and systemic symptoms experienced by patients with IBS. The results offer mechanisms underlying the efficacy of the low FODMAP diet in IBS.     

Cross‐cultural and psychological issues in irritable bowel syndrome

Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal disorders encountered by gastroenterologists worldwide. Of all the etiological factors that had been postulated to explain the pathophysiology of IBS, cultural and psychological factors are unique and difficult to understand. Culture plays an important role in coloring the presentation of IBS, and many a times, it has a significant role in several treatment aspects too. Psychological aspects like personality profiles, family relationships, societal myths, and abuse in any form are equally important in the management perspectives of IBS. In this brief review, we had tried to specifically focus on these aspects in IBS and have explained the evidences in favor of these factors. Knowledge about various cross‐cultural aspects and psychological factors in patients with IBS is essential for taking an appropriate history and for undertaking a holistic approach for the management of the same. A collaborative team effort by psychiatrists and gastroenterologists could help in reducing the burden of this difficult to treat functional bowel disorder.     

Bugs and irritable bowel syndrome: The good,the bad and the ugly

Recently, there has been strong interest in the therapeutic potential of probiotics for irritable bowel syndrome (IBS). At the same time, there is a rapidly growing body of evidence to support an etiological role for gastrointestinal infection and the associated immune activation in the development of post‐infectious IBS. In a more controversial area, small intestinal bacterial overgrowth has been associated with a subset of patients with IBS; the issue of whether it is appropriate to treat a subset of IBS patients with antibiotics and probiotics is currently a matter for debate. Thus, it appears that the gastrointestinal microbial flora may exert beneficial effects for symptoms of IBS under some circumstances, while in other situations gut microbes could give rise to symptoms of IBS. How do we make sense of the apparently diverse roles that ‘bugs’ may play in IBS? To address this question, we have conducted an in‐depth review, attempting where possible to draw lessons from Asian studies.     

Associations among gut permeability,inflammatory markers,and symptoms in patients with irritable bowel syndrome

Background

Alterations in gastrointestinal (GI) permeability and immune measures are present in some patients with irritable bowel syndrome (IBS) but the relationship to symptoms is poorly defined. In adults with IBS, we compared permeability, unstimulated peripheral blood monocyte (PBMC) interleukin-10 (IL-10) levels, IBS life interference, and GI and psychological distress symptoms.

Methods

In 88 women and 18 men with IBS, GI permeability was quantitated as percent recovery of urinary sucrose and the lactulose/mannitol (L/M) ratio. IL-10 was measured in supernatants from 72-h incubated, unstimulated PBMCs. Participants completed a 4-week daily diary recording IBS life interference on daily activities and work, IBS symptoms, and psychological distress symptoms. They also completed the Brief Symptom Inventory.

Results

The L/M ratio but not percent sucrose recovery was significantly correlated with IBS interference with activities and work and retrospectively measured anxiety and depression. Unstimulated PBMC production of IL-10 correlated significantly with IBS interference with daily work, IBS symptom score, and abdominal pain. We identified a subgroup of IBS subjects with higher IL-10 and/or higher L/M ratio who had substantially higher IBS interference and IBS symptom scores.

Conclusions

Our findings suggest a distinct subgroup of IBS patients with alterations in gut barrier function. This subgroup is characterized by increased GI permeability and/or increased PBMC production of IL-10. These physiologic alterations reflect more severe IBS as measured by interference of IBS with daily activities and daily IBS symptoms.     

Prevalencia de síntomas de intestino irritable en población asistente a centros comerciales de Santiago de Chile

BackgroundIrritable bowel syndrome (IBS) is a functional gastrointestinal disorder characterized by abdominal pain or discomfort that is associated with altered bowel habit. Both its prevalence and clinical characteristics vary throughout Latin America. A percentage of patients does not seek medical attention, therefore a reliable prevalence figure can only be established by interviewing non-selected populations.AimsTo study the prevalence and clinical characteristics of IBS symptoms in non-selected subjects in Santiago, Chile.MethodsA total of 437 shopping mall visitors above the age of 15 years (246 women) participated in the study by answering the Rome II validated questionnaire for IBS. The demographic and socioeconomic backgrounds, comorbidities, and a family history of IBS were registered.ResultsA total of 64.1% subjects reported having gastrointestinal symptoms and 28.6% had symptoms suggestive of IBS. When the subjects with IBS symptoms were compared with the asymptomatic individuals, a predominance of women (65.6 vs. 42.9, P<.001) and a greater cholecystectomy frequency (33.6 vs. 12.9% P<.05) were observed in the former. The age of symptom onset was 30.4 years. An equal percentage of subjects (42.4%) presented with diarrhea and constipation and 15.2% presented with alternating IBS. Participants with a higher educational level reported a lower percentage of IBS (P<.05). A family history of the disease was present in 40% of the subjects with IBS, compared with 14.9% in the asymptomatic individuals (P<.05). Only 39.2% of the subjects had seen a physician for their symptoms and the treatment and tests ordered were inappropriate.ConclusionThe prevalence of IBS symptoms in the population studied is one of the highest described. Therefore, health teams should have the necessary knowledge and skill required for its management.     

Colonoscopy as an adjunctive method for the diagnosis of irritable bowel syndrome: Focus on pain perception

Background and Aim: Visceral hypersensitivity is an important component of the pathophysiology of irritable bowel syndrome (IBS). In the present study, we investigated differences in pain perception during colonoscopy between IBS patients and non‐IBS patients. We further assessed the sensitivity, specificity, and predictive values of pain scores to diagnose IBS. Methods: Patients who underwent colonoscopy for the evaluation of gastrointestinal symptoms or for screening purposes were included. All patients completed Rome III criteria questionnaires and reported pain scores on 0–100‐mm visual analog scales after colonoscopy. The patients were divided into three groups: (i) IBS; (ii) other functional gastrointestinal disorders (FGID), including functional bloating, functional diarrhea, and functional constipation; and (iii) healthy controls. Results: A total of 217 patients were included. The pain scores (median, interquartile range) of IBS patients (52, 34–71) were higher than those of the healthy controls (22, 12–35) or other FGID patients (18, 10–29) (P < 0.001). Upper gastrointestinal symptoms were observed more often in the IBS group than in the non‐IBS group (83.2% vs 34.5%, P < 0.001). At the pain score level of 31, the sensitivity, specificity, positive predictive value, and negative predictive value for IBS diagnosis were 86.1%, 75.9%, 75.7%, and 86.3%, respectively. Conclusions: The degree of pain perception during colonoscopy was higher in IBS patients than in non‐IBS patients. We concluded that colonoscopy can be useful in identifying IBS patients, with the additional benefit of excluding organic disorders of the lower gastrointestinal tract.