Chronic Idiopathic Diarrhea Research Articles

Late presentations and missed opportunities among newly diagnosed HIV patients presenting to a specialty clinic in Lebanon

Late presentation to medical care of individuals infected with the human immunodeficiency virus (HIV) is linked to poor outcomes and increased morbidity and mortality. Missed opportunities for a prompt diagnosis are frequently reported among late presenters. We aimed to estimate the proportion of late presenters and missed opportunities in diagnosis among newly diagnosed HIV-positive subjects presenting to a specialty clinic in Lebanon. This is a retrospective chart review of all newly diagnosed adult HIV-positive subjects presenting to clinic from 2012 to 2022. Demographic, laboratory, and clinical data were collected at initial HIV diagnosis or presentation to medical care. We defined late presentation as having a CD4 count < 350 or AIDS-defining event regardless of CD4 count. Advanced disease is defined as having a CD4 count below 200 cells/μL or the presence of an AIDS-defining illness, regardless of the CD4 count. A missed opportunity was defined as the presence of an indicator condition (IC) that suggests infection with HIV/AIDS during 3 years preceding the actual HIV diagnosis and not followed by a recommendation for HIV testing. The proportions for demographic, epidemiological, and clinical characteristics are calculated by excluding cases with missing information from the denominator. Our cohort included 150 subjects (92.7% males; 63.6% men who have sex with men (MSM); 33.3% heterosexuals; median age 30.5 years at diagnosis). 77 (51.3%) were late presenters and 53 (35.3% of all subjects, 68.8% of late presenters) had advanced HIV on presentation. Up to 76.5% of late presenters had a presentation with an HIV-related condition at a healthcare provider without getting HIV test within the previous 3 years. The most frequent ICs were weight loss, generalized lymphadenopathy, constitutional symptoms, and chronic idiopathic diarrhea. Overall mortality rate was 4% (6/150 individuals). All-cause mortality among those who presented with AIDS was 15.4% (6/39 subjects). In our setting, late presentations and missed opportunities for HIV diagnosis are common. In the Middle East, AIDS mortality remains high with a large gap in HIV testing. To effectively influence policies, comprehensive analyses should focus on estimating the preventable health and financial burdens of late HIV presentations. Another concern pertains to healthcare providers’ attitudes and competencies.

Opioids in the Treatment of Chronic Idiopathic Diarrhea in Humans—A Systematic Review and Treatment Guideline

In patients with chronic idiopathic diarrhea resistant to standard treatment, opioids are often used as rescue therapy. This systematic review investigated opioid effects on gut function in chronic diarrhea. PubMed and Embase were searched regarding effects of opioid agonists on the gastrointestinal tract in humans with chronic or experimentally induced diarrhea. A total of 1472 relevant articles were identified and, after thorough evaluation, 11 clinical trials were included. Generally, studies reported a reduction in stool frequency and an increase in transit time during treatment with the opioid receptor agonists loperamide, asimadoline, casokefamide, and codeine compared with placebo. Loperamide and diphenoxylate significantly improved stool consistency compared with placebo, whereas asimadoline showed no such effects. Compared with placebo, loperamide treatment caused less abdominal pain and urgency. Asimadoline showed no significant subjective improvements, but fedotozine was superior to placebo in reducing abdominal pain and bloating in selected patients. Only two relevant studies were published within the last 20 years, and standardized endpoint measures are lacking. Most trials included few participants, and further evidence is needed from larger, prospective studies. Likewise, consensus is needed to standardize endpoints for stool frequency, transit time, and consistency to conduct future meta-analyses on opioids in management of chronic idiopathic diarrhea.

The effect of photobiomodulation therapy on the management of chronic idiopathic large-bowel diarrhea in dogs.

To evaluate photobiomodulation therapy's effectiveness (PBMT) in managing chronic idiopathic large-bowel diarrhea. Thirty dogs were selected and divided into a control (CG) and treatment group (TG). CG received psyllium husk at the dose of 4 tablespoons/day for 30days. TG received PBMT with a Class IV therapeutic laser, divided into three sessions on week 1, two sessions on week 2, and one session on week 3. A daily log of fecal characteristics was maintained, and on days 0, 8, 15, and 30, a canine inflammatory bowel disease index (CIBDAI) and body condition scores (BCS) were obtained. Results were compared using a Mann-Whitney test. Multiple regression was run to predict CIBDAI, Bristol stool scores, and diarrhea from different parameters. The Kaplan-Meier test was used to compare the occurrence rate of ≥ 1day of diarrhea and ≥ 2days of diarrhea by 30days. Cox regression analysis to investigate interest covariates influences the same outcome. A p < 0.05 was set. The sample included 15 Belgian Malinois Shepherd Dogs, 10 German Shepherd Dogs, and 5 Dutch Shepherd Dog, with a mean age of 3.6 ± 2.3years and a bodyweight of 24.6 ± 8.0kg. TG showed an improvement in all scores and clinical signs, increased body weight, and BCS. An increased time of appearance of a second episode of diarrhea was observed in both groups. Activity level contributed to the prediction of defecation frequency and CIBDAI. PBMT significantly improved clinical signs and frequency of diarrhea episodes compared to psyllium husk.

Fecal Bacterial Microbiota of Healthy Free-Ranging, Healthy Corralled, and Chronic Diarrheic Corralled Rhesus Macaques (Macaca mulatta).

A clinical challenge to nearly every primate facility in North America is chronic idiopathic diarrhea (CID), the pathogenesis of which has yet to be fully elucidated. However, wild macaques appear resistant to CID, a trend that we observed in the free-ranging population of the Caribbean Primate Research Center. The gastrointestinal microbiota has been shown to have a significant role in the pathogenesis of disease and in maintaining normal health and development of the gut. In humans, chronic diarrhea is associated with alteration of the gut microbiota, which has lower bacterial diversity than does the microbiota of healthy humans. The current study was designed to describe and compare the fecal bacterial microbiota of healthy corralled, CID corralled, and healthy, free-ranging macaques. Fresh fecal samples were collected from healthy corralled (HC; n = 30) and CID (n = 27) rhesus macaques and from healthy macaques from our free-ranging colony (HF; n = 43). We excluded macaques that had received antibiotics during the preceding 60 d (90 d for healthy animals). Bacterial DNA was extracted, and the V4 region of the 16S rRNA gene was sequenced and compared with known databases. The relative abundance of Proteobacteria was higher in CID animals than HC animals, but otherwise few differences were found between these 2 groups. HF macaques were differentially enriched with Christensenellaceae and Helicobacter, which are highly associated with a 'healthy' gut in humans, as compared to corralled animals, whereas CID animals were enriched with Proteobacteria, which are associated with dysbiosis in other species. These results indicate that environment has a greater influence than health status on the gut microbiota. Furthermore, the current data provided targets for future studies on potential clinical interventions, such as probiotics and fecal transplants.

Yield of Diagnostic Tests and Effects of Crofelemer for Chronic Idiopathic Diarrhea In Non-HIV Patients

Yield of Diagnostic Tests and Effects of Crofelemer for Chronic Idiopathic Diarrhea In Non-HIV Patients

Is irritable bowel syndrome also present in dogs?

Irritable bowel syndrome (IBS) in humans is described as the recurrent presence of gastrointestinal signs, without gross histopathologic evidence of inflammation and of other morphologic lesions; however, it is a syndrome not unanimously defined in veterinary medicine. There is some evidence that dysmotility could be related to stressors in some dogs that present with clinical signs (e.g. chronic idiopathic large-bowel diarrhea) that share overlapping aspects with human IBS. The authors hypothesize that an IBS-like condition, similar to that described in humans, might also be present in dogs. Nevertheless, the diagnostic path for canine IBS needs to be further elucidated and its pathogenesis better defined for a more rational therapeutic approach.

Evaluation of oral serum-derived bovine immunoglobulins in HIV-infected patients with chronic idiopathic diarrhea

ObjectivesTo evaluate serum-derived bovine immunoglobulin/protein isolate (SBI) for safety and impact on gastrointestinal (GI) symptoms in HIV patients with chronic idiopathic diarrhea.MethodsA multi-center trial comprised of a double-blind, placebo (PBO)-controlled lead-in phase, (participants received PBO or SBI at 2.5 or 5.0 g BID for 4 weeks) followed by a 20-week, PBO-free phase (SBI at either 2.5 or 5.0 g BID). Participants included HIV-infected patients who were virologically suppressed with a history of chronic idiopathic diarrhea, defined as > 3 loose stools per day for ≥ 3 months without an identifiable cause. Safety was evaluated by monitoring adverse events (AEs) and clinical laboratory testing. Health status and changes in GI symptoms were assessed using validated questionnaires.ResultsSBI was well tolerated by the 103 participants with only 2 withdrawals due to AEs potentially associated with SBI. Mean number of daily unformed stools decreased from about 4 at baseline to less than 2 by week 4 for all study groups. Improvements in several other GI symptoms were also reported. Comparison of the PBO group to SBI groups showed no significant differences, although both SBI cohorts reported significantly improved health status scores. GI symptom improvements were maintained throughout the 20-week PBO-free phase.ConclusionsOral SBI is safe and well tolerated at the doses studied in HIV patients with chronic diarrhea. No conclusions could be drawn regarding impact on GI symptoms. Additional studies are ongoing to examine the biological and immunologic effects of SBI in virologically suppressed HIV-infected patients.

Lanreotide Autogel in the Treatment of Idiopathic Refractory Diarrhea: Results of an Exploratory, Controlled, Before and After, Open-label, Multicenter, Prospective Clinical Trial

PurposeChronic idiopathic diarrhea is the passage of loose stools >3 times daily, or a stool weight >200 g/d, persisting for >4 weeks without clear clinical cause. Patients refractory to standard anti-diarrhetics have limited treatment options. Somatostatin analogues have the ability to reduce gastrointestinal secretions and motility. This study evaluated the efficacy and safety of lanreotide Autogel* 120 mg in chronic idiopathic diarrhea. MethodsOther anti-diarrhetics were not allowed during the study and were stopped at screening. Patients received lanreotide Autogel 120 mg at baseline and day 28. Stool frequency and consistency (Bristol Stool Scale) were recorded; quality of life (QoL) was assessed using the 36-item Short Form Health Survey and irritable bowel syndrome QoL questionnaires; adverse events were monitored. The primary outcome was the proportion of patients with a reduction of ≥50% or normalization to a mean of ≤3 stools/d at day 28. FindingsThirty-three patients with >3 stools/d at baseline were included; mean (SD) age was 55.2 (16.4) years. Fourteen patients (42.4%) had a response to lanreotide Autogel at day 28 and 17 (51.5%) at day 56. Mean (SD) number of stools decreased significantly from 5.7 (2.2) at baseline to 3.7 (2.2) at day 56 overall (n = 32; P < 0.001). Significant and clinically meaningful improvements in disease-specific QoL were found in the overall populations. No new safety signals emerged. ImplicationsLanreotide Autogel 120 mg decreased symptoms in these patients with chronic idiopathic refractory diarrhea, and meaningfully improved QoL. These finding have to be confirmed in further clinical trials. ClinicalTrials.gov Identification: NCT00891371; Eudract CT 2009-009356-20

Probiotics for Human and Poultry Use in the Control of Gastrointestinal Disease: A Review of Real-World Experiences

Over a century ago Eli Metchnikoff proposed the revolutionary idea to consume viable bacteria to promote health by modulating the intestinal microflora. The idea is more applicable now than ever, since bacterial antimicrobial resistance has become a serious worldwide problem both in medical and agricultural fields. The interest in digestive physiology and the microbiome has generated data whereby well being of all living organisms with a digestive tract can be enhanced and the risk of disease reduced. Given the recent international legislation and domestic consumer pressures to withdraw growth-promoting antibiotics and limit antibiotics available for treatment of bacterial infections, probiotics can offer alternative options. Probiotics are live microorganisms that, when administered in adequate amounts, confer a health benefit on the host. Current indications are that mechanism of action involves a number of possibilities like rapid activation of innate host immune responses, assisting in the digestion of food materials etc. In this review, we focused on applying probiotic concept to alleviate chronic constipation and idiopathic diarrhea in humans or for specific pathogen reduction and improvement of GIT diseases in poultry. Based on this review, it is clear that the probiotic concept can be further explored to impact various areas of health and well being in both humans and animals

Common biostructure of the colonic microbiota in neuroendocrine tumors and Crohnʼs disease and the effect of therapy

The aims were to comparatively investigate the biostructure of colonic microbiota in patients with neuroendocrine tumors and Crohn's disease (CD) and to study the response of the microbiota to therapy. Sections of fecal cylinders from 66 patients with neuroendocrine tumors (NET; 25 foregut, 30 midgut, 11 hindgut), 50 patients with CD (Crohn's Disease Activity Index [CDAI] ≥150), and 30 patients with chronic idiopathic diarrhea seen at the Charité Hospital and 25 healthy controls were investigated using fluorescence in situ hybridization with probes specific for five bacterial groups: Faecalibacterium prausnitzii, Clostridium group XIVa / Roseburia group, Bacteroides, Enterobacteriaceae, and Bifidobacteriaceae. We found a striking F. prausnitzii (Fprau) depletion in the stool of patients with NET of the midgut and patients with CD. The changes of the microbiota in the two other NET groups were uncharacteristic and similar to those observed in patients with chronic idiopathic diarrhea. Fprau depletion was reversible with chemotherapy and with interferon alpha-2b treatment in patients with midgut NET. Somatostatin analogs had no influence on Fprau concentrations. Patients with NET and CD show similarities in their abnormalities of the fecal biostructure. Interferon alpha and systemic chemotherapy significantly improved the fecal biostructure in patients with midgut NET.

Functional biostructure of colonic microbiota (central fermenting area, germinal stock area and separating mucus layer) in healthy subjects and patients with diarrhea treated with Saccharomyces boulardii

The colonic content can be compared to a spatially structured high output bioreactor composed of three functionally different regions: a separating mucus layer, a germinal stock area, and a central fermenting area. The stool mirrors this structure and can be used for diagnosis in health and disease. In a first part, we introduce a novel method based on fluorescence in situ hybridization (FISH) of sections of punched-out stool cylinders, which allows quantitatively monitor microbiota in the mucus, the germinal stock and the central fermenting areas. in a second part, we demonstrate the practical implementation of this method, describing the biostructure of stool microbiota in healthy subjects and patients with chronic idiopathic diarrhea treated with Saccharomyces boulardii. Punched stool cylinders from 20 patients with chronic idiopathic diarrhea and 20 healthy controls were investigated using fluorescence in situ hybridization. Seventy-three bacterial groups were evaluated. Fluctuations in assembly of 11 constitutive bacterial groups were monitored weekly for 3 weeks prior to, 3 weeks during, and 3 weeks after oral Saccharomyces boulardii supplementation. Typical findings in healthy subjects were a 5-60 μm mucus separating layer; homogeneous distribution and fluorescence, high concentrations (>10 × 10(10) bacterial/mL) of the three habitual bacterial groups: Bacteroides, Roseburia and Faecalibacterium prausnitzii; and low concentrations of the occasional bacterial groups. The diarrhea could be described in terms of increased separating effort, purging, decontamination, bacterial substitution. Typical findings in diarrhea were: increased thickness of the protective mucus layer, its incorporation in the stool, absolute reduction in concentrations of the habitual bacterial groups, suppression of bacterial metabolism in the central fermenting area (hybridization silence), stratification of the stool structure by watery ingredients, and substitutive increase in the concentrations of occasional bacterial groups. The microbial and clinical symptoms of diarrhea were reversible with Saccharomyces boulardii therapy. The structure-functional analysis of stool microbiota allows to quantitatively monitor colonic malfunction and its response to therapy. Saccharomyces boulardii significantly improves the stool biostructure in patients with chronic idiopathic diarrhea and has no influence on the stool microbiota in healthy subjects.

Treatment of chronic idiopathic large-bowel diarrhea in dogs with a highly digestible diet and soluble fiber: a retrospective review of 37 cases.

The medical records of 37 dogs diagnosed with chronic idiopathic large-bowel diarrhea were reviewed. The median age of affected dogs was 6 years. The median body weight was 13.9 kg. The median duration of clinical signs before diagnosis was 32 weeks. Diarrhea usually was intermittent and characterized by increasing frequency, fecal mucus, hematochezia, and tenesmus. Vomiting was common but usually much less frequent and severe than the diarrhea. A variety of stressful factors and abnormal personality traits were identified. CBC and serum biochemistry usually were normal. Fecal examination rarely identified parasites. Rectal cytology specimens were most often normal, but some dogs had increased numbers of neutrophils. The colonic mucosa often was normal during colonoscopy, but decreased numbers of lymphoid follicles were found in some dogs. Histopathologic evaluation found that colonic mucosa was within normal limits. Treatment with soluble fiber (Metamucil) added to a highly digestible diet (Hills i/d) resulted in a very good to excellent response in most dogs. The median initial dosage of Metamucil was 2 tablespoons (2 T) per day. In some dogs, the fiber dosage was reduced or eliminated, or a grocery store brand of dog food was substituted, without causing diarrhea to return.

Biostructure of Fecal Microbiota in Healthy Subjects and Patients With Chronic Idiopathic Diarrhea

Dysbiosis is a key component of intestinal disorders. Our aim was to quantitatively access the biostructure of fecal microbiota in healthy subjects and patients with chronic idiopathic diarrhea and evaluate the responses to Saccharomyces boulardii treatment. We investigated punched fecal cylinders from 20 patients with chronic idiopathic diarrhea and 20 healthy controls using fluorescence in situ hybridization. Fluctuations in assembly of 11 bacterial groups were monitored weekly for 3 weeks before, during, and after oral S boulardii supplementation. The structural organization of fecal microbiota in healthy subjects was stable and unaffected by S boulardii. The assembly of fecal microbiota in idiopathic diarrhea was markedly different, characterized by mucus depositions within feces; mucus septa and striae; marked reduction in concentrations of habitual Eubacterium rectale, Bacteroides, and Faecalibacterium prausnitzii groups; suppression of bacterial fluorescence in the center of the feces; increased concentrations and spatial shift of mucotrop bacteria to the fecal core; and increased concentrations of occasional bacteria. Except for elevated concentrations of some occasional bacterial groups, all parameters typical for diarrhea improved significantly with S boulardii treatment and most changes persisted after cessation of therapy. The improvement of the fecal microbiota was accompanied by partial (40%) and complete normalization (30%) of the diarrheal symptoms. The fecal microbiota is highly structured. Fluorescence in situ hybridization analysis allowed us to quantitatively study the dysbiotic changes. S boulardii significantly improved the fecal biostructure in patients with diarrhea but had no influence on the feces in healthy subjects.

Factitious Diarrhea Induced by Stimulant Laxatives: Accuracy of Diagnosis by a Clinical Reference Laboratory Using Thin Layer Chromatography

Surreptitious ingestion of laxatives can lead to serious factitious diseases that are difficult to diagnose. Most cases involve ingestion of bisacodyl or senna. Thin layer chromatography (TLC) of urine or stool is the only commercially available test for these laxatives. Such testing is considered highly reliable, but its accuracy in clinical practice is unknown. Our aim was to evaluate the reliability of TLC laxative testing by a clinical reference laboratory in the United States. Diarrhea was induced in healthy volunteers by ingestion of bisacodyl, senna, or a control laxative (n = 11 for each laxative group). Samples of urine and diarrheal stool were sent in blinded fashion to the clinical reference laboratory for bisacodyl and senna analysis. TLC testing for bisacodyl-induced diarrhea revealed a sensitivity of 73% and specificity of 91% when urine was tested and sensitivity and specificity of 91% and 96%, respectively, when stool was analyzed. When diarrhea was induced by senna, the TLC assay for senna failed to identify even a single urine or stool specimen as positive (zero% sensitivity). Considering the expected prevalence of surreptitious laxative abuse in patients with chronic idiopathic diarrhea (2.4%-25%, depending on the clinical setting), TLC of urine or stool for bisacodyl by this reference laboratory would often produce misleading results, and testing for senna would have no clinical value. The major problems are false-positive tests for bisacodyl and false-negative tests for senna.

Chronic diarrhea

Chronic diarrhea

Treatment of Chronic Idiopathic Large‐Bowel Diarrhea in Dogs with a Highly Digestible Diet and Soluble Fiber: A Retrospective Review of 37 Cases

The medical records of 37 dogs diagnosed with chronic idiopathic large‐bowel diarrhea were reviewed. The median age of affected dogs was 6 years. The median body weight was 13.9 kg. The median duration of clinical signs before diagnosis was 32 weeks. Diarrhea usually was intermittent and characterized by increasing frequency, fecal mucus, hematochezia, and tenesmus. Vomiting was common but usually much less frequent and severe than the diarrhea. A variety of stressful factors and abnormal personality traits were identified. CBC and serum biochemistry usually were normal. Fecal examination rarely identified parasites. Rectal cytology specimens were most often normal, but some dogs had increased numbers of neutrophils. The colonic mucosa often was normal during colonoscopy, but decreased numbers of lymphoid follicles were found in some dogs. Histopathologic evaluation found that colonic mucosa was within normal limits. Treatment with soluble fiber (Metamucil) added to a highly digestible diet (Hills i/d) resulted in a very good to excellent response in most dogs. The median initial dosage of Metamucil was 2 tablespoons (2 T) per day. In some dogs, the fiber dosage was reduced or eliminated, or a grocery store brand of dog food was substituted, without causing diarrhea to return.

The Self-limited Nature of Chronic Idiopathic Diarrhea

The Self-limited Nature of Chronic Idiopathic Diarrhea

Chronic Idiopathic Diarrhea

Chronic diarrhea is defined as passage of loose stools for more than 4 weeks. In most instances the cause of chronic diarrhea can be discovered and treated effectively. A few less common causes also play a role: laxative abuse, small bowel bacterial overgrowth, and even bile acid malabsorption. Rarer syndromes account for a much smaller percentage of chronic diarrheas but may be more difficult to identify and treat. In a small number of patients, a cause for chronic diarrhea cannot be found and they are said to have chronic idiopathic secretory diarrhea, a fairly homogeneous disorder that can be sporadic or epidemic. This disorder can be diagnosed after excluding other causes of chronic diarrhea; it is associated with moderate weight loss and gradually subsides after 1.5–3 years. A sensible approach to the patient with chronic diarrhea of unexplained cause is based on a comprehensive history, focusing on the stool characteristics (watery, bloody, fatty), the occurrence of weight loss, aggravating and mitigating factors (with special emphasis on the diet); on a thorough physical examination and on the careful use of selected laboratory investigations such as complete blood count, comprehensive metabolic panel, thyroid tests, and of course stool tests such as bacterial cultures and extensive search for parasites; electrolytes, pH, occult blood test, leukocytes (or lactoferrin/calprotectin) and fat assessment. Subsequent analysis will depend on the findings from history, physical exam, and stool analysis and may or may not include more aggressive investigations such as CT enterography, small bowel follow-through radiograms, and videocapsule enteroscopy. Additional tests may have to be occasionally utilized, including plasma peptides (chromogranin, gastrin, calcitonin, VIP, somatostatin) and urine chemistry tests (5-HIAA, metanephrines, histamine).

The self-limited nature of chronic idiopathic diarrhea.

Little is known about the clinical presentation and natural history of previously healthy patients in whom chronic idiopathic diarrhea develops. We reviewed the case records of 152 patients with chronic diarrhea who had no history of gastrointestinal surgery and who were evaluated in detail as part of a chronic-diarrhea protocol from 1985 to 1990. Patients were considered to have chronic idiopathic diarrhea if they had persistently loose stools for more than four weeks, no systemic illness, and no identifiable cause of diarrhea. Seventeen patients (10 men and 7 women) ranging in age from 33 to 72 years met the criteria for chronic idiopathic diarrhea. Each patient had a history of a relatively abrupt onset of symptoms, often soon after returning home from a trip, starting two to seven months before evaluation. Their diarrhea did not occur during a local outbreak of diarrhea, and other family members did not become ill. Stool frequency ranged from 5 to 25 movements per day, stool weights ranged from 417 to 1480 g per day, and fecal electrolyte and osmolality values were consistent with a diagnosis of secretory diarrhea. The results of biopsies of the small intestine and colon were normal, as were small-bowel roentgenograms. Extensive studies for infectious causes of diarrhea were negative, and no patient responded to antibiotic therapy. In every patient the diarrhea stopped without specific therapy after 7 to 31 months (mean, 15) and did not recur during a follow-up period averaging 38 months. Sporadic idiopathic chronic diarrhea is a recognizable syndrome that can last many months, but is self-limited.

An evaluation of the significance of microscopic colitis in patients with chronic diarrhea.

Some patients with chronic idiopathic diarrhea have an apparent nonspecific inflammation of colonic mucosa, even though their colons appear normal by barium enema and colonoscopy. This has been referred to as microscopic colitis. However, the significance of this finding is unclear, because the ability of pathologists to accurately distinguish mild degrees of abnormality has not been established. Furthermore, even if the mucosa of these patients is nonspecifically inflamed, it is not known whether this is associated with deranged colonic function that could contribute to the development of chronic diarrhea. To assess these questions, we first examined colonic biopsy specimens in a blinded fashion, comparing biopsy results from patients with microscopic colitis with biopsy specimens from subjects in two control groups. This analysis revealed that colonic mucosa from six patients with microscopic colitis was in fact abnormal. For example, their mucosa contained an excess of both neutrophiles and round cells in the lamina propria, cryptitis, and reactive changes. These and other differences were statistically significant. Second, colonic absorption, measured by the steady state nonabsorbable marker perfusion method, was severely depressed in the patients. For example, mean water absorption rate was 159 ml/h in normal subjects and was reduced to only 26 ml/h in six patients with microscopic colitis. Results of net and unidirectional electrolyte fluxes and of electrical potential difference suggested that colonic fluid absorption was abnormal because of reduced active and passive sodium and chloride absorption and because of reduced Cl/HCO3 exchange. Small intestinal fluid and electrolyte absorption was abnormally reduced in two of the six patients, suggesting the possibility of coexistent small intestinal involvement in some of these patients. We conclude that nonspecific inflammation of colonic mucosa is associated with a severe reduction of colonic fluid absorption, and that the latter probably contributes to the development of chronic diarrhea.