Association of intestinal inflammation and permeability markers with clinical manifestations of Parkinson's disease.

INTRODUCTION: Intestinal inflammation and gut microbiota dysbiosis can stimulate degeneration of dopaminergic neurons and development of Parkinson's disease (PD) via the gut-brain axis in certain patients. METHODS: In a case-control study, fecal markers of intestinal inflammation and permeability were measured using the ELISA method in PD patients and healthy controls. Motor and nonmotor symptoms were assessed using the Movement Disorder Society (MDS) Unified PD Rating Scale, Hoehn & Yahr scale, MDS Non-Motor Symptom Scale, Scales for Outcomes in PD - Autonomic Dysfunction, PD Sleep Scale - 2, Montreal Cognitive Assessment, Beck Anxiety Inventory, and Beck Depression Inventory-II. A correlation was established between the intestinal inflammation and permeability markers and PD symptoms. RESULTS: Higher levels of beta-defensin 2, zonulin and lactoferrin were recorded in PD patients compared to controls. Calprotectin and secretory immunoglobulin A showed no significant differences. Regression analysis indicated the roles of beta-defensin 2 and lactoferrin in predicting PD likelihood. Calprotectin yielded positive correlations with disease duration, depression, motor fluctuations, and gastrointestinal symptoms; beta defensin 2 with thermoregulation; and secretory immunoglobulin A with depression. Secretory immunoglobulin A showed negative correlation with age and age at disease onset, while zonulin showed negative correlation with the MDS Unified PD Rating Scale total score. CONCLUSIONS: Fecal markers differed in PD patients compared to controls and correlated with age, disease duration, and some nonmotor symptoms. Future studies should identify the subgroups of PD patients that are likely to develop intestinal inflammation.

Characterization of Early and Late Damage in a Mouse Model of Pelvic Radiation Disease.

Pelvic radiation disease (PRD), a frequent side effect in patients with abdominal/pelvic cancers treated with radiotherapy, remains an unmet medical need. Currently available preclinical models have limited applications for the investigation of PRD pathogenesis and possible therapeutic strategies. In order to select the most effective irradiation protocol for PRD induction in mice, we evaluated the efficacy of three different locally and fractionated X-ray exposures. Using the selected protocol (10 Gy/day × 4 days), we assessed PRD through tissue (number and length of colon crypts) and molecular (expression of genes involved in oxidative stress, cell damage, inflammation, and stem cell markers) analyses at short (3 h or 3 days after X-ray) and long (38 days after X-rays) post-irradiation times. The results show that a primary damage response in term of apoptosis, inflammation, and surrogate markers of oxidative stress was found, thus determining a consequent impairment of cell crypts differentiation and proliferation as well as a local inflammation and a bacterial translocation to mesenteric lymph nodes after several weeks post-irradiation. Changes were also found in microbiota composition, particularly in the relative abundance of dominant phyla, related families, and in alpha diversity indices, as an indication of dysbiotic conditions induced by irradiation. Fecal markers of intestinal inflammation, measured during the experimental timeline, identified lactoferrin, along with elastase, as useful non-invasive tools to monitor disease progression. Thus, our preclinical model may be useful to develop new therapeutic strategies for PRD treatment.

Alterations in circulating markers in HIV/AIDS patients with poor immune reconstitution: Novel insights from microbial translocation and innate immunity.

After long-term anti-retroviral therapy (ART) treatment, most human immunodeficiency virus (HIV)/Acquired Immure Deficiency Syndrome (AIDS) patients can achieve virological suppression and gradual recovery of CD4+ T-lymphocyte (CD4+ T cell) counts. However, some patients still fail to attain normal CD4+ T cell counts; this group of patients are called immune non-responders (INRs), and these patients show severe immune dysfunction. The potential mechanism of poor immune reconstitution (PIR) remains unclear and the identification of uniform biomarkers to predict the occurrence of PIR is particularly vital. But limited information is available on the relationship between circulating markers of INRs and immune recovery. Hence, this review summarises alterations in the intestine microbiota and associated markers in the setting of PIR to better understand host-microbiota-metabolite interactions in HIV immune reconstitution and to identify biomarkers that can predict recovery of CD4+ T cell counts in INRs.

Can the Prognosis of COVID-19 Disease Be Determined by Fecal Markers and Cytokines?

The coronavirus disease 2019 (COVID-19) pandemic has affected the entire world, and has a variety of clinical presentations. The aim of this study is to determine the relationships of fecal cytokines and markers with the symptoms and prognosis of children with COVID-19 infection, and to identify noninvasive markers during follow-up. In a cohort of 40 COVID-19-positive children and 40 healthy controls, fecal cytokines and markers were examined in stool samples. A binary logistic model was used to assess the potential of cytokines as risk factors for hospitalization. Odds ratios (ORs) with 95% confidence intervals (CIs) were reported. A P-value <0.05 was accepted as statistically significant. Levels of fecal lysozyme, myeloperoxidase, hemoglobin, and interleukin-5 (IL-5) (P < 0.05) were significantly higher among the patients than controls. In a logistic regression analysis, fecal IL-2 (OR = 3.83; 95% CI: 1.44-15.92), IL-4 (OR = 2.96; 95% CI: 1.09-12.93), IL-5 (OR = 4.56; 95% CI: 1.18-27.88), IL-10 (OR = 2.71 95% CI: 1.19-7.94), interferon-gamma (IFN-γ) (OR = 4.03; 95% CI: 1.44-15.73), IFN-α (OR = 3.02; 95% CI: 1.08-11.65), calcium-binding protein B S100 (S100 B) (OR = 4.78; 95% CI: 1.31-27.82), neutrophil elastase (NE) 2 (OR = 4.07; 95% CI: 1.17-19.69), and matrix metalloproteinase 1 (MMP-1) (OR = 3.67; 95% CI: 1.1-18.82) levels were significantly higher in hospitalized patients with COVID-19 infection than outpatients. We demonstrated that various fecal cytokines and markers were increased in patients who had COVID-19. Fecal IL-2, IL-4, IL-5, IL-10, IFN-γ, IFN-α, S100 B, NE, and MMP-1 levels were significantly elevated in hospitalized patients. We suggest that the fecal and serum levels of cytokines could be used to predict the prognosis of COVID-19 disease, although more studies are needed to confirm this.

Fecal Lactoferrin and Other Putative Fecal Biomarkers in Crohn's Disease: Do They Still Have a Potential Clinical Role?

INTRODUCTION: The need for noninvasive markers of disease activity is mandatory in the assessment of Crohn's disease (CD). The most widely fecal biomarker in CD, despite several limits, is fecal calprotectin. This review aims to elucidate the role, if any, of all other fecal biomarkers, as alternative tools for assessing clinical and endoscopic disease activity, and predict capsule endoscopy findings, response to therapy, disease relapse, and postoperative recurrence. These fecal biomarkers included lactoferrin, S100A12, high mobility group box 1, neopterin, polymorphonuclear neutrophil elastase, fecal hemoglobin, alpha1-antitrypsin, lysozyme, human beta-defensin-2, neutrophil gelatinase-associated lipocalin, matrix metalloproteinase-9, chitinase 3-like-1, M2-pyruvate kinase, myeloperoxidase, and eosinophil proteins. METHODS: A systematic electronic search in the medical literature was performed up to April 2020. Seventy eligible studies were identified out of 859 citations. Data were grouped according to the assessment of clinical and endoscopic disease activity, capsule endoscopy findings, response to therapy, prediction of relapse, and postoperative recurrence. RESULTS: The overall correlation between lactoferrin and clinical indexes is poor, while performance is good with endoscopic scores. Lactoferrin seems to represent a reasonably good surrogate marker of response to therapy and to be potentially useful in identifying patients at high risk for endoscopic relapse or postoperative recurrence. The evaluation of the performance of all other fecal markers is limited by the lack of adequate data. CONCLUSIONS: None of the fecal markers so far represents an acceptable alternative to calprotectin in clinical practice. Fecal lactoferrin is the only possible exception, but a more extensive investigation is still required.

Disturbed microbial ecology in Alzheimer's disease: evidence from the gut microbiota and fecal metabolome.

BACKGROUND: Gut microbiota (GMB) alteration has been reported to influence the Alzheimer's disease (AD) pathogenesis through immune, endocrine, and metabolic pathways. This study aims to investigate metabolic output of the dysbiosis of GMB in AD pathogenesis. In this study, the fecal microbiota and metabolome from 21 AD participants and 44 cognitively normal control participants were measured. Untargeted GMB taxa was analyzed through 16S ribosomal RNA gene profiling based on next-generation sequencing and fecal metabolites were quantified by using ultrahigh performance liquid chromatography-mass spectrometry (UPLC-MS). RESULTS: Our analysis revealed that AD was characterized by 15 altered gut bacterial genera, of which 46.7% (7/15 general) was significantly associated with a series of metabolite markers. The predicted metabolic profile of altered gut microbial composition included steroid hormone biosynthesis, N-Acyl amino acid metabolism and piperidine metabolism. Moreover, a combination of 2 gut bacterial genera (Faecalibacterium and Pseudomonas) and 4 metabolites (N-Docosahexaenoyl GABA, 19-Oxoandrost-4-ene-3,17-dione, Trigofoenoside F and 22-Angeloylbarringtogenol C) was able to discriminate AD from NC with AUC of 0.955 in these 65 subjects. CONCLUSIONS: These findings demonstrate that gut microbial alterations and related metabolic output changes may be associated with pathogenesis of AD, and suggest that fecal markers might be used as a non-invasive examination to assist screening and diagnosis of AD.

Is fecal calprotectin an accurate marker in the management of Crohn's disease?

Although lacking validated cutoff values, fecal calprotectin (FC), besides C-reactive protein, is considered the standard test for assessing disease activity in Crohn's disease (CD). The aim of the present review is to provide a general overview of the literature addressing the role of FC in the clinical and endoscopic assessment of disease activity in CD, seeking correlations with capsule endoscopy, response to therapy, prediction of relapse, and postoperative recurrence. A systematic search of the literature up to September 2019 was performed using Medline, Embase, and the Cochrane Library. Only papers written in English concerning FC in adult patients affected by CD were included. Pediatric studies, in vitro studies, animal studies, studies on blood/serum samples, and studies analyzing FC in ulcerative colitis or in both CD and ulcerative colitis were excluded. Out of 713 citations, 65 eligible studies were identified. FC showed high accuracy in the assessment of intestinal inflammation and response to therapy, in particular in colonic disease, thus proving a good surrogate marker for these aims. FC is useful in identifying patients at high risk for endoscopic relapse or postoperative recurrence, for optimizing or downstage therapy. Unfortunately, FC performs less well in small bowel CD. FC is an effective fecal marker in the management of CD patients, optimizing the use of endoscopic procedures. Owing to its diagnostic accuracy, FC may represent a cornerstone of the "treat-to-target" management strategy of CD patients.

Urbanization Impacts the Physicochemical Characteristics and Abundance of Fecal Markers and Bacterial Pathogens in Surface Water.

Urbanization is increasing worldwide and is happening at a rapid rate in China in line with economic development. Urbanization can lead to major changes in freshwater environments through multiple chemical and microbial contaminants. We assessed the impact of urbanization on physicochemical characteristics and microbial loading in canals in Suzhou, a city that has experienced rapid urbanization in recent decades. Nine sampling locations covering three urban intensity classes (high, medium and low) in Suzhou were selected for field studies and three locations in Huangshan (natural reserve) were included as pristine control locations. Water samples were collected for physicochemical, microbiological and molecular analyses. Compared to medium and low urbanization sites, there were statistically significant higher levels of nutrients and total and thermotolerant coliforms (or fecal coliforms) in highly urbanized locations. The effect of urbanization was also apparent in the abundances of human-associated fecal markers and bacterial pathogens in water samples from highly urbanized locations. These results correlated well with land use types and anthropogenic activities at the sampling sites. The overall results indicate that urbanization negatively impacts water quality, providing high levels of nutrients and a microbial load that includes fecal markers and pathogens.

Fecal markers in the management of inflammatory bowel disease.

Inflammatory bowel disease (IBD) is characterized by periods of symptomatic remission and relapse. Diagnosis and assessment of IBD are based on clinical evaluation, serum parameters, radiology, and endoscopy. Fecal markers have emerged as new diagnostic tools to detect and monitor intestinal inflammation. Fecal calprotectin (FC) and lactoferrin (FL) were identified decades ago as potentially revolutionary markers for IBD. Following these discoveries numerous additional markers, including S100A12, M2-PK, metalloproteinases, hemoglobin, myeloperoxidase, lysozyme, polymorphonuclear elastase, neopterin, and nitric oxide, have also been suggested as novel markers of IBD. But only FC and FL are used for the management of clinical IBD patients. The objective of this review is to introduce the clinical applications of fecal markers in the diagnosis, monitoring and prediction of outcomes of inflammatory bowel disease.

Surrogate Fecal Biomarkers in Inflammatory Bowel Disease: Rivals or Complementary Tools of Fecal Calprotectin?

Background: Current noninvasive methods for assessing intestinal inflammation in inflammatory bowel disease (IBD) remain unsatisfactory. Along with C-reactive protein and erythrocyte sedimentation rate, fecal calprotectin (FC) is the standard test for assessing IBD activity, even though its specificity and accuracy are not optimal and it lacks a validated cutoff. Over the past few decades, several fecal markers released from intestinal inflammatory cells have been investigated in IBD; they are the subject of this systematic review. Methods: A systematic electronic search of the English literature up to April 2017 was performed using Medline and the Cochrane Library. Only papers written in English that analyzed fecal biomarkers in IBD were included. In vitro studies, animal studies, studies on blood/serum samples, and studies analyzing FC or fecal lactoferrin alone were excluded. Results: Out of 1023 citations, 125 eligible studies were identified. Data were grouped according to each fecal marker including S100A12, high-mobility group box 1, neopterin, polymorphonuclear neutrophil elastase, fecal hemoglobin, alpha1-antitrypsin, human neutrophil peptides, neutrophil gelatinase-associated lipocalin, chitinase 3-like-1, matrix metalloproteinase 9, lysozyme, M2-pyruvate kinase, myeloperoxidase, fecal eosinophil proteins, human beta-defensin-2, and beta-glucuronidase. Some of these markers showed a high sensitivity and specificity and correlated with disease activity, response to therapy, and mucosal healing. Furthermore, they showed a potential utility in the prediction of clinical relapse. Conclusions: Several fecal biomarkers have the potential to become useful tools complementing FC in IBD diagnosis and monitoring. However, wide variability in their accuracy in assessment of intestinal inflammation suggests the need for further studies.

Fecal marker levels as predictors of need for endoscopic balloon dilation in Crohn's disease patients with anastomotic strictures.

AIM: To evaluate the accuracy and best cut-off value of fecal calprotectin (FC) and fecal lactoferrin (FL) to predict disease recurrence in asymptomatic patients presenting with anastomotic strictures. METHODS: This was a longitudinal single tertiary center study based on prospectively collected data (recorded in a clinical database created for this purpose) performed between March 2010 and November 2014. Crohn's disease (CD) patients with anastomotic stricture who submitted to postoperative endoscopic evaluation were included. Stools were collected on the day before bowel cleaning for FC and FL. Endoscopic balloon dilation (EBD) was performed if the patient presented an anastomotic stricture not traversed by the colonoscope, regardless of patients' symptoms. Successful dilation was defined as passage of the colonoscope through the dilated stricture into the neotermimal ileum. Postoperative recurrence was defined as a modified Rutgeerts score of ≥ i2b. RESULTS: In a total of 178 patients who underwent colonoscopy, 58 presented an anastomotic stricture, 86% were asymptomatic, and 48 (54% male; median age of 46.5 years) were successfully dilated. Immediate success rate was 92% and no complications were recorded. FC and FL levels correlated significantly with endoscopic recurrence (P < 0.001) with an optimal cut-off value of 90.85 µg/g (sensitivity of 95.5%, specificity of 69.2%, positive predictive value (PPV) of 72.4%, negative predictive value (NPV) of 94.7% and accuracy of 81%] for FC and of 5.6 µg/g (sensitivity of 77.3%, specificity of 69.2%, PPV of 68%, NPV of 78.4% and accuracy of 72.9%) for FL. CONCLUSION: Fecal markers are good predictors of CD endoscopic recurrence in patients with asymptomatic anastomotic stricture. FC and FL may guide the need for EBD in this context.

An update on diagnostic and prognostic biomarkers in inflammatory bowel disease.

INTRODUCTION: Diagnosis of the chronic inflammatory bowel diseases relies upon initial recognition of an inflammatory condition, followed by definitive endoscopic, histological and radiological investigations. Various biomarkers are available to assist with initial elucidation of an inflammatory process: these also have important roles after diagnosis in monitoring and ongoing assessment of progress. Areas covered: Various inflammatory markers, serological tests and genetic analyses may be helpful in predicting the course of disease in the coming months. This review provides an update on the current understanding and knowledge about these markers. It also highlights key gaps and identifies aspects that require further study. Expert commentary: Our current approach to the application of non-invasive biomarkers is rudimentary. Further work is required to elucidate the roles of the various markers.

Fecal biomarkers in inflammatory bowel disease.

Over the last two decades, knowledge on fecal biomarkers has substantially increased. Nowadays, these non-invasive markers of inflammation have significant clinical utility in the management of inflammatory bowel disease. Their use informs the decision to perform endoscopy before diagnosis is made right through to influencing therapeutic choices and the need for interval endoscopic assessment. In this review, the roles of two S100 proteins, calprotectin, and S100A12 are described along with that of lactoferrin, in the context of inflammatory bowel disease.

Accuracies of fecal calprotectin, lactoferrin, M2-pyruvate kinase, neopterin and zonulin to predict the response to infliximab in ulcerative colitis.

BACKGROUND: Fecal markers might predict the response to anti-TNFα in ulcerative colitis (UC). AIMS: To compare the performance of fecal calprotectin (fCal), lactoferrin (fLact), M2-PK (fM2-PK), neopterin (fNeo), and zonulin (fZon) to predict the response to therapy in active UC patients. METHODS: Disease activity from 31 consecutive patients with an active UC, treated with infliximab (IFX) was assessed by the Mayo score at baseline and at week 14 and by the partial Mayo score at W52 and stool samples collected for fecal marker measurements at W0, W2, and W14. RESULTS: At W14, 19 patients (61%) were responders to IFX induction. The median levels of fCal, fLact and fM2-PK drop dramatically from baseline to W14 in clinical responders. At W2, fM2-PK, fLact and fCal levels predicted accurately the response to IFX induction. At W14, fLact, fCal, and fM2-PK were individually reliable markers to predict sustained response at W52. The performances of fNeo and fZon were weaker in this setting. CONCLUSIONS: The performance of fM2-PK at W2 to predict response to induction therapy with IFX was superior to that of fLact and fCal, whereas monitoring fLact was the best tool to predict adequately the course of the disease at one year under maintenance IFX in UC.

Progress in the treatment and outcome of pediatric inflammatory bowel disease patients.

INTRODUCTION: The number of pediatric patients with inflammatory bowel disease (IBD), namely Crohn´s disease, ulcerative colitis and unclassified colitis, has rapidly increased in Western countries. Areas covered: This review discusses how the treatment of pediatric IBD patients has improved,with attention given to therapeutic quality and cost. The literature search covers Medline-PubMed and the Cochrane Library, with February 2016 as the last search dates. Similarly to what has been the trend in the management of adult IBD, pediatric IBD therapy has become more active than before. High use of immunosuppressants and the availability of biological therapeutic agents has helped to control the extensive and aggressive course of pediatric IBD. Full disease control at an early phase has advantages such as preserving normal child growth and development, maintaining overall good health and quality of life, as well as decreasing the psychosocial burden of the disease. Expert commentary: A key research direction is to tailor treatment modalities according to anticipated individual phenotype and disease course. Another is to reduce healthcare costs by decreasing the so-far high rate of surgery of pediatric IBD patients, and, instead, to develop a more active approach to treatment than before.

Evaluation of biomarkers for ulcerative colitis comparing two sampling methods: fecal markers reflect colorectal inflammation both macroscopically and on a cellular level.

OBJECTIVE: Simple, objective and inexpensive tools for the assessment of mucosal inflammation in ulcerative colitis (UC) are highly desirable. The aim of this study was to evaluate a broad spectrum of activity markers comparing two sampling methods: fecal samples and the mucosal patch technique. METHODS: Twenty patients with active UC and 14 healthy controls were characterized by means of clinical indices and endoscopy together with histology and immunohistochemistry on colorectal sections. Neutrophil myeloperoxidase (MPO), calprotectin, eosinophil cationic protein (ECP), eosinophil protein X (EPX/EDN) and IL-1ß were analyzed in fecal samples and rectal fluid collected by the patch technique. Nitric oxide (NO) was analyzed in rectal gas samples. Expression of activity markers on colorectal neutrophils and eosinophils were analyzed by flow cytometry. RESULTS: All fecal and patch markers were increased in UC patients compared with healthy controls. Fecal markers and the level of neutrophil activation correlated to disease activity, whereas patch markers did not. The best markers in terms of discriminative power were fecal MPO and IL-1ß. Fecal marker levels were related to sigmoidal histology scores and to neutrophil number and activation. Patch markers were related to rectal inflammation only. CONCLUSIONS: The levels of inflammation markers in feces and patch fluid distinctly reflected active inflammation in UC. The degree of disease activity was however best assessed by fecal markers, particularly MPO and IL-1ß. Fecal markers reflect colorectal inflammation both macroscopically and on a cellular level, and may be useful for the evaluation of subclinical inflammation. The applicability of patch markers is restricted to rectal inflammation.

Assessment of disease activity in pediatric ulcerative colitis.

To date, we encounter more and more pediatric patients with ulcerative colitis (UC). For yet unclear reasons, UC in pediatric patients seems to be a more aggressive and extensive disease than in their adult counterparts. In the majority of pediatric patients, the disease presents as pancolitis. The severity of the disease is reflected in the high use of corticosteroids and immunosuppressants and a high rate of surgery for medically refractory patients. The means by which to assess disease activity or to accurately predict its course are far from optimal. This review summarizes the current knowledge on the means for assessing UC activity in children. Research for developing new tools by which to monitor and forecast disease activity, are needed in all areas including invasive endoscopy, clinical evaluation, and treatment follow-up.

Relevance of fecal calprotectin and lactoferrin in the post-operative management of inflammatory bowel diseases.

The role of fecal lactoferrin and calprotectin has been extensively studied in many areas of inflammatory bowel disease (IBD) patients' management. The post-operative setting in both Crohn's disease (CD) and ulcerative colitis (UC) patients has been less investigated although few promising results come from small, cross-sectional studies. Therefore, the current post-operative management still requires endoscopy 6-12 mo after intestinal resection for CD in order to exclude endoscopic recurrence and plan the therapeutic strategy. In patients who underwent restorative proctocolectomy, endoscopy is required whenever symptoms includes the possibility of pouchitis. There is emerging evidence that fecal calprotectin and lactoferrin are useful surrogate markers of inflammation in the post-operative setting, they correlate with the presence and severity of endoscopic recurrence according to Rutgeerts' score and possibly predict the subsequent clinical recurrence and response to therapy in CD patients. Similarly, fecal markers show a good correlation with the presence of pouchitis, as confirmed by endoscopy in operated UC patients. Fecal calprotectin seems to be able to predict the short-term development of pouchitis in asymptomatic patients and to vary according to response to medical treatment. The possibility of both fecal markers to used in the routine clinical practice for monitoring IBD patients in the post-operative setting should be confirmed in multicentric clinical trial with large sample set. An algorithm that can predict the optimal use and timing of fecal markers testing, the effective need and timing of endoscopy and the cost-effectiveness of these as a strategy of care would be of great interest.

Elevated fecal levels of eosinophil granule proteins predict collagenous colitis in patients referred to colonoscopy due to chronic non-bloody diarrhea.

OBJECTIVE: Colonoscopy with biopsy sampling is often performed to detect collagenous colitis (CC) and lymphocytic colitis (LC) in patients with chronic non-bloody diarrhea. However, the diagnostic yield is low and incurs high costs. Fecal calprotectin (FC) and myeloperoxidase (MPO) indicate intestinal inflammation in ulcerative colitis (UC) and Crohn's disease (CD). In CC, elevated fecal levels of eosinophil protein X (EPX) and eosinophil cationic protein (ECP) have been reported. We aimed to evaluate if F-EPX, F-ECP, FC, and F-MPO could predict the diagnostic outcome in patients with chronic non-bloody diarrhea referred to colonoscopy. We also evaluated serum (S) EPX and ECP in this regard. METHODS: Of 67 included patients, 63 (94%) underwent colonoscopy with biopsy sampling. Fecal EPX, F-ECP, FC, F-MPO, S-EPX, and S-ECP were analyzed. RESULTS: Diagnostic outcome: normal: n = 46 (73%), CC: n = 9 (14%), LC: n = 4 (6%), UC: n = 2 (3%), CD: n = 2 (3%). Higher levels of F-EPX and F-ECP were found in CC compared to a normal diagnostic outcome (p = 0.01). No change was noted in any of the fecal markers in LC. When all of the fecal markers were normal the probability of a normal diagnostic outcome was 92%. We found no differences in S-EPX and S-ECP between the groups. CONCLUSION: Elevated F-EPX and F-ECP could predict CC. None of the fecal markers predicted LC. Serum-EPX and S-ECP are not useful for the diagnosis of CC, LC, UC, or CD. With normal levels in all of the analyzed fecal markers, there is a low probability of a pathologic diagnostic outcome.