Colorectal Inflammation is Well Predicted by Fecal Calprotectin in Children with Gastrointestinal Symptoms

In cystic fibrosis (CF), cystic fibrosis transmembrane regulator (CFTR) dysfunction leads to digestive disorders that promote intestinal inflammation and dysbiosis enhancing gastrointestinal symptoms. In pancreatic insufficiency CF patients, both intestinal inflammation and dysbiosis, are associated with an increase in the fecal calprotectin (FC) level. However, associations between the FC level, gastrointestinal symptoms, and quality of life (QoL) remain poorly studied. We aimed to assess such associations in pancreatic insufficiency CF children. The FC level was measured in pancreatic insufficiency CF children’s stool samples. Children and their parents completed two questionnaires: The Gastrointestinal Symptoms Scales 3.0-PedsQLTM and the Quality of Life Pediatric Inventory 4.0-PedsQLTM. Lower scores indicated worse symptomatology or QoL. Thirty-seven CF children were included. A FC level above 250 µg/g was associated with worse gastrointestinal symptoms and QoL scores. The FC level was inversely correlated with several gastrointestinal scores assessed by children (i.e., Total, “Heart Burn Reflux”, “Nausea and Vomiting”, and “Gas and Bloating”). Several QoL scores were correlated with gastrointestinal scores. The FC level was weakly associated with clinical parameters. Some gastrointestinal and QoL scores were related to disease severity associated parameters. In CF, the FC level, biomarker previously related to intestinal inflammation and dysbiosis, was associated with worse digestive symptoms and QoL scores.

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Elevated fecal and serum calprotectin in COVID-19 are not consistent with gastrointestinal symptoms

Scientific Reports ◽

10.1038/s41598-021-01231-4 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Hajar Shokri-Afra ◽

Ahmad Alikhani ◽

Bahman Moradipoodeh ◽

Farshid Noorbakhsh ◽

Hafez Fakheri ◽

...

Keyword(s):

Intestinal Inflammation ◽

Cell Damage ◽

Gastrointestinal Symptoms ◽

Fecal Calprotectin ◽

Severe Illness ◽

Intestinal Epithelial ◽

Inflammation Marker ◽

Gi Symptoms ◽

The Relationship ◽

Patient Subgroups

AbstractIntestinal epithelial cell damage caused by SARS-CoV-2 infection was thought to be associated with gastrointestinal symptoms and decreased fecal consistency. The association of the gastrointestinal symptoms with the COVID-19-mediated inflammatory response triggered by the gastrointestinal immune system was investigated in this paper. Intestinal inflammation marker fecal calprotectin along with serum calprotectin and other inflammatory markers were measured in COVID-19 cases with and without GI manifestations as well as healthy individuals. Analyses were performed to compare COVID-19 patient subgroups and healthy controls and examine the relationship between fecal and serum calprotectin levels with gastrointestinal symptoms and disease severity. COVID-19 patients (n = 70) were found to have markedly elevated median levels of fecal (124.3 vs. 25.0 µg/g; P < 0/0001) and serum calprotectin (3500 vs. 1060 ng/mL; P < 0/0001) compared with uninfected controls. Fecal and serum calprotectin levels were not significantly different between COVID-19 patients who displayed GI symptoms and those who did not. Compared with other acute phase markers, both fecal and serum calprotectin were superior in identifying COVID-19 patients who progressed to severe illness. Although the progression of COVID-19 disease is marked by an elevation of fecal and serum calprotectin, gastrointestinal symptoms or diarrhea were not correlated with calprotectin increase level.

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The Therapeutic Effect of a Multistrain Probiotic on Diarrhea-Predominant Irritable Bowel Syndrome: A Pilot Study

Gastroenterology Research and Practice ◽

10.1155/2018/8791916 ◽

2018 ◽

Vol 2018 ◽

pp. 1-8 ◽

Cited By ~ 1

Author(s):

Seok-Hoon Lee ◽

Nam-Seok Joo ◽

Kwang-Min Kim ◽

Kyu-Nam Kim

Keyword(s):

Irritable Bowel Syndrome ◽

Statistical Significance ◽

Information Service ◽

Gastrointestinal Symptoms ◽

Bacterial Overgrowth ◽

Fecal Calprotectin ◽

Beneficial Bacteria ◽

Research Information ◽

Fecal Microbiome ◽

Irritable Bowel

Backgrounds. Recent studies suggest that diarrhea-predominant irritable bowel syndrome (IBS) is associated with intestinal bacterial microflora, colonic inflammation, and small intestinal bacterial overgrowth (SIBO). The purpose of this study was to evaluate the effect of a multistrain probiotic intake on these associated factors in patients with diarrhea-predominant IBS. Methods. The recruited volunteers were adults who were diagnosed with diarrhea-predominant IBS according to the Rome III criteria. After 8 weeks of probiotic ingestion, changes in gastrointestinal symptoms, fecal microbiome, SIBO, and fecal calprotectin were determined. Results. There was an increase in beneficial bacteria (41.2 ± 16.8% vs. 53.7 ± 15.3%, P=0.018) and a decrease in harmful bacteria (13.0 ± 13.9% vs. 4.7 ± 4.0%, P=0.010) in the microbial stool analysis. The SIBO prevalence also decreased at the end of treatment. However, the average levels of fecal calprotectin showed a decreasing tendency, without reaching statistical significance (364.4 ± 729.1 mg/kg vs. 200.9 ± 347.6 mg/kg, P=0.375). Conclusion. Treatment with a multistrain probiotic for 8 weeks led to significant increases in beneficial bacteria in the gut as well as the improvement of gastrointestinal symptoms. This study is registered at the Clinical Research Information Service (KCT0002906).

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Normal fecal calprotectin levels in healthy children are higher than in adults and decrease with age

Paediatrics & Child Health ◽

10.1093/pch/pxz070 ◽

2019 ◽

Vol 25 (5) ◽

pp. 286-292

Author(s):

Marta Velasco Rodríguez-Belvís ◽

Javier Francisco Viada Bris ◽

Carmen Plata Fernández ◽

Alberto García-Salido ◽

Julia Asensio Antón ◽

...

Keyword(s):

Negative Correlation ◽

Gastrointestinal Disease ◽

Gastrointestinal Symptoms ◽

Fecal Calprotectin ◽

Primary Health Care Centre ◽

Positive Finding ◽

Healthy Children ◽

Anthropometric Data ◽

Health Care Centre ◽

Cross Sectional

Abstract Background/Objectives The paediatric reference range of fecal calprotectin (FC) has not been decisively established and previous studies show a wide within-age variability, suggesting that other factors like anthropometric data or type of feeding can influence FC. Our aims were to establish the normal levels of FC in healthy children grouped by age and analyze whether sex, gestational age, birth weight, type of delivery, type of feeding, or anthropometric data influence FC values. Methods This multicentre, cross-sectional, and observational study enrolled healthy donors under 18 years of age who attended their Primary Health Care Centre for their routine Healthy Child Program visits. The exclusion criteria were: (i) immunodeficiency, (ii) autoimmune or (iii) gastrointestinal disease; (iv) medication usage; (v) gastrointestinal symptoms; or (vi) positive finding in the microbiological study. Results We enrolled 395 subjects, mean age was 4.2 years (range 3 days to 16.9 years), and 204 were male. The median FC was 77.0 mcg/g (interquartile range 246). A negative correlation between age and FC was observed (Spearman’s rho = −0.603, P<0.01), and none of the other factors analyzed were found to influence FC levels. Conclusions Normal FC values in healthy children (particularly in infants) are higher than those considered to be altered in adults and show a negative correlation with age. It is necessary to reconsider the upper limits of FC levels for paediatric patients according to age, with further studies required to determine other factors that influence FC during infancy.

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Fecal Calprotectin Levels for the Ethiological Diagnosis in Brazilian Patients With Gastrointestinal Symptoms

The American Journal of Gastroenterology ◽

10.14309/00000434-201410002-01689 ◽

2014 ◽

Vol 109 ◽

pp. S500

Author(s):

Lorete Kotze ◽

Renato Nisihara ◽

Murilo Cavassani ◽

Sandra Valarini ◽

Paulo Kotze

Keyword(s):

Gastrointestinal Symptoms ◽

Fecal Calprotectin

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Utility of Fecal Calprotectin in Evaluation of Chronic Gastrointestinal Symptoms in Primary Care

Clinical Pediatrics ◽

10.1177/0009922817744607 ◽

2017 ◽

Vol 57 (9) ◽

pp. 1058-1063 ◽

Cited By ~ 4

Author(s):

Ramya Ramraj ◽

Amy Garcia ◽

David Mosen ◽

Lisa Waiwaiole ◽

Ning Smith

Keyword(s):

Primary Care ◽

Care Setting ◽

Primary Care Setting ◽

Intestinal Inflammation ◽

Gastrointestinal Symptoms ◽

Fecal Calprotectin ◽

Primary Indication ◽

Inflammatory Bowel ◽

Excellent Tool

Fecal calprotectin (FC) is a marker of intestinal inflammation. Data are limited on utility of routine FC testing in pediatric primary care. Participants 0 to 18 years old who had an FC test in the years 2010-2014 were retrospectively identified. Those with less than a year of follow-up or a prior diagnosis of inflammatory bowel disease (IBD) were excluded. In all, 84% (689/822) had normal FC; no participant with normal FC was diagnosed with IBD in the subsequent 12 months. Also, 16% (133/822) had elevated FC, and 31% of those (42/133) were diagnosed with IBD. FC values for IBD and non-IBD groups were 1084 µg/g (interquartile range [IQR] = 514.4-2000) and 27.05 µg/g (IQR = 15.6-62.6; P < .001), respectively. Abdominal pain was the primary indication. In this cohort, sensitivity of FC for IBD is 100%, and specificity is 88%. The FC test can be an excellent tool in the primary care setting to exclude IBD and avoid unnecessary referrals and colonoscopies.

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SAT0388 CHROMOENDOSCOPY AND MAGNIFICATION COLONOSCOPY: ANALYSIS OF THE MUCOSA OF THE COLON AND ILEUM IN PATIENTS WITH SPONDYLOARTRHITIS AND GASTROINTESTINAL SYMPTOMS WITHOUT INFLAMMATORY BOWEL DISEASE

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.3943 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1142.2-1143

Author(s):

C. Florez ◽

V. Parra-Izquierdo ◽

W. Bautista-Molano ◽

Y. M. Chamorro-Melo ◽

A. Beltrán-Ostos ◽

...

Keyword(s):

Intestinal Inflammation ◽

Gastrointestinal Symptoms ◽

Fecal Calprotectin ◽

Inflammatory Back Pain ◽

Vascular Pattern ◽

Gastrointestinal Involvement ◽

Histological Techniques ◽

Asas Criteria ◽

The Government ◽

Axial Involvement

Background:Digital chromoendoscopy with magnification is a technique that identify microscopic inflammation, with a better characterize, highlighting specific gastrointestinal findings showing a good correlation with histopathological features. Spondyloarthritis (SpA) patients with the presence of non-specific gastrointestinal symptoms, subclinical intestinal inflammation is defined by endoscopic and histological techniquesObjectives:To detect early structural inflammatory changes by chromoendoscopy and magnification colonoscopy in colonic/ileum digestive mucosa and establish its association with clinical variables in patients with SpA and gastrointestinal symptomsMethods:In total, 180 patients with SpA (ASAS/criteria) were assessed by rheumatologists, of which (n=35) (19.4%) had an indication by a gastroenterologist to perform the chromoendoscopy, magnification colonoscopy and histological analysis. The association between clinical and colonoscopy variables were evaluated using the Chi square or Fisher’s exact test. (Ethical/Code. 2017-023)Results:The average age of the patients included for colonoscopy was 45.4±10.3 years, 57.1% were men and 42.9% presented the HLA-B*27 allele. Axial involvement (91.4%), inflammatory back pain (68.6%) and use of biological therapy (71.4%). High levels of calprotectin (25.7%), CRP>3 (14.3%), positive ESR (22.9%) and positive ANCA (8.6%) was observed. Regarding outcome measures of function and activity, BASDAI >4 (60%) and ASDAS-PCR >2.1 (80.0%) was observedThe loss of vascular pattern in the ileum was associated with high levels of calprotectin levels (p=0.002). At microscopic level, 80% of the patients who presented acute inflammation in the ileum had elevated calprotectin (p=0.013). Cryptitis (77.8%) in the ileum was associated with axial involvement (p=0.017). Ulcers and erosion in the ileum were associated with positive ESR (p=0.003). All patients who presented ulcerations and inflammation (64.3%) in ileum were HLA-B27 positive (p=0.029) and (p=0.052) respectively. The 50% of patients with atrophy of villi in ileum were receiving biological treatment (p=0.035)Conclusion:Digital chromoendoscopy and augmentation colonoscopy provided an improved and detailed contrast of the surface of the gastrointestinal mucosa. The tissue sampling showed the loss of vascular pattern as main finding in ileum with interesting associations with fecal calprotectin levels in patients with SpA. The interest of proposing the active search for symptoms, signs and biomarkers of gastrointestinal involvement in patients with SpA without IBD is to define subclinical gastrointestinal involvement and early remission through an endoscopic evaluation and objective histological and propose a specific clinical and therapeutic treatment.Acknowledgments:The Government Institute of Science, Technology, and Innovation, Francisco Jose de Caldas—COLCIENCIAS(Grant No. 130877757442). Universidad El Bosque (PCI-2018-10091), Hospital Militar Central (Grant 2017-023), Clínicos IPS, Gastroadvanced, Fundación Instituto de Reumatología Fernando Chalem-Bogota, Colombia and Biomedicina de Chihuahua, MéxicoDisclosure of Interests:None declared

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Calprotectin as a marker of bowel inflammation

10.7287/peerj.preprints.65v1 ◽

2013 ◽

Author(s):

Gianluca Terrin ◽

Andrea Pietravalle

Keyword(s):

Inflammatory Process ◽

Intestinal Inflammation ◽

Inflammatory Diseases ◽

Functional Gastrointestinal Disorders ◽

Gastrointestinal Symptoms ◽

Fecal Calprotectin ◽

Bacterial Degradation ◽

Human Neutrophils ◽

Gastrointestinal Disorders ◽

Non Invasive

In the last years the need for a non-invasive diagnostic tool that would help to discriminate between organic and functional gastrointestinal disorders directed research towards potential immunological markers. A great number of non-invasive bio-markers has been proposed, including eosinophilic cationic protein, elastase, esterase, myeloperoxidase, lysozyme, lactoferrin, and calprotectin. Compared to other biomarkers, calprotectin (also called MRP8/14, calgranulin A/B , S100 A8/A9) may offer advantages based on its biological characteristics. Calprotectin is a 36.5-kDa, calcium and zinc binding polypeptide which constitutes about 60% of soluble cytosol proteins in human neutrophils. It is also found in monocytes, keratinocytes, muscle tissue and infiltrating tissue macrophages. When bound to calcium it becomes resistant to proteolysis and colonic bacterial degradation. This make is stable for up to 1 week at room temperature and facilitate its determination in feces. Calprotectin is involved in the regulation of the inflammatory process, participate to the early innate immune response and exert antimicrobial, anti-proliferative and apoptotic properties. Fecal calprotectin is a direct measure of mucosal inflammation activity and becomes detectable when intestinal inflammation is still at an insufficient level to cause an increase in serum inflammation markers. In the last decade fecal calprotectin has been proposed as a marker to rule out acute and chronic intestinal inflammatory diseases in children with typical gastrointestinal symptoms. Many studies demonstrated its diagnostic utility in identifying children and adults with inflammatory bowel disease and correlate with the degree of disease activity. The detection of elevated levels of fecal calprotectin in healthy infants during the first few weeks of age, limits their use as screening test for intestinal inflammatory diseases in early life. Despite this evidence, the measurement of calprotectin in the serum has been proposed to identify neonates with necrotizing enterocolitis. Recent studies have shown higher fecal calprotectin levels in infants with irritable bowel syndrome and colics, compared with healthy controls. Additionally, a correlation was found between fecal calprotectin concentration and IBS clinical presentation severity. However, these studies do not provide data on diagnostic accuracy in distinguish between organic and functional gastrointestinal disorders. Despite significant limitations, these evidences suggest the presence of a subtle inflammatory process underlying functional gastrointestinal disorders and open new perspectives on their pathogenesis. Fecal calprotectin may play a role that could be revealed in further, specifically designed, studies. Changes in microflora, permeability, calprotectin excretion and other inflammatory biomarkers, should be investigated to clarify if a continuum exists between inflammatory conditions and intestinal functional diseases.

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The Role of Fecal Calprotectin in Patients with Systemic Sclerosis and Small Intestinal Bacterial Overgrowth (SIBO)

Diagnostics ◽

10.3390/diagnostics10080587 ◽

2020 ◽

Vol 10 (8) ◽

pp. 587

Author(s):

Beata Polkowska-Pruszyńska ◽

Agnieszka Gerkowicz ◽

Karol Rawicz-Pruszyński ◽

Dorota Krasowska

Keyword(s):

Systemic Sclerosis ◽

Gastrointestinal Symptoms ◽

Bacterial Overgrowth ◽

Small Intestinal Bacterial Overgrowth ◽

Fecal Calprotectin ◽

Hydrogen Breath Test ◽

Noninvasive Test ◽

Intestinal Bacterial Overgrowth ◽

Small Intestinal

Fecal calprotectin (FC) is a quick, cost-effective, and noninvasive test, which is used to diagnose patients with active inflammatory bowel diseases (IBD). Recent studies suggest the possible predictive role of FC in the diagnosis of small intestinal bacterial overgrowth (SIBO) in patients with systemic sclerosis (SSc). This study aimed to assess the predictive value of FC in SSc patients and its’ possible use as a SIBO marker. A total of 40 SSc patients and 39 healthy volunteers were enrolled in the study. All subjects completed questionnaires evaluating gastrointestinal symptoms, FC measurements, and lactulose hydrogen breath test (LHBT) assessing SIBO presence. After rifaximin treatment, patients with SIBO underwent the same diagnostic procedures. Significantly higher FC values were observed in the study group compared to controls (97 vs. 20 μg/g; p < 0.0001) and in SSc patients diagnosed with SIBO compared to SSc patients without SIBO (206 vs. 24 μg/g; p = 0.0010). FC turned out to be a sensitive (94.12%) and specific (73.68%) marker in the detection of SIBO in patients with SSc (AUC = 0.82, 95% CI = 0.66–0.93; p < 0.0001). Our study suggests the potential value of FC in SSc in detecting gastrointestinal impairment and its promising role as an additional diagnostic tool for SIBO.

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