Bacterial gut dysbiosis is associated with Crohn’s disease symptoms but not with elevated fecal calprotectin

Abstract Background This multicenter prospective study (UMIN000019958) aimed to evaluate the usefulness of serum leucin-rich alpha-2 glycoprotein (LRG) levels in monitoring disease activity in inflammatory bowel disease (IBD). Methods Patients with moderate-to-severe IBD initiated on adalimumab therapy were enrolled herein. Serum LRG, C-reactive protein (CRP), and fecal calprotectin (fCal) levels were measured at week 0, 12, 24, and 52. Colonoscopy was performed at week 0, 12, and 52 for ulcerative colitis (UC), and at week 0, 24, and 52 for Crohn’s disease (CD). Endoscopic activity was assessed using the Simple Endoscopic Score for Crohn’s Disease (SES-CD) for CD and the Mayo endoscopic subscore (MES) for UC. Results A total of 81 patients was enrolled. Serum LRG levels decreased along with improvements in clinical and endoscopic outcomes upon adalimumab treatment (27.4 ± 12.6 μg/ml at week 0, 15.5 ± 7.7 μg/ml at week 12, 15.7 ± 9.6 μg/ml at week 24, and 14.5 ± 6.8 μg/ml at week 52), being correlated with endoscopic activity at each time point (SES-CD: r = 0.391 at week 0, r = 0.563 at week 24, r = 0.697 at week 52; MES: r = 0.534 at week 0, r = 0.429 at week 12, r = 0.335 at week 52). Endoscopic activity better correlated with LRG compared to CRP and fCal on pooled analysis at all time points (SES-CD: LRG: r = 0.636, CRP: r = 0.402, fCal: r = 0.435; MES: LRG: r = 0.568, CRP: 0.389, fCal: r = 0.426). Conclusions Serum LRG is a useful biomarker of endoscopic activity both in CD and UC during the adalimumab treatment.

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Combined evaluation of fecal calprotectin and C-reactive protein as a therapeutic target in the management of patients with Crohn's disease

Gastroenterología y Hepatología (English Edition) ◽

10.1016/j.gastre.2020.04.010 ◽

2021 ◽

Vol 44 (2) ◽

pp. 87-95

Author(s):

Francisco Guilherme Cancela Penna ◽

Rodrigo Macedo Rosa ◽

Fernando H. Pereira ◽

Pedro Ferrari Sales Cunha ◽

Stella Cristina S. Sousa ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Therapeutic Target ◽

Fecal Calprotectin ◽

C Reactive Protein ◽

Reactive Protein ◽

Combined Evaluation

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The Role of Laboratory Tests in Crohn's Disease

Clinical Medicine Insights Gastroenterology ◽

10.4137/cgast.s38203 ◽

2016 ◽

Vol 9 ◽

pp. CGast.S38203 ◽

Cited By ~ 8

Author(s):

Maria Cappello ◽

Gaetano Cristian Morreale

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Laboratory Tests ◽

Molecular Mechanisms ◽

Latent Tuberculosis ◽

Fecal Calprotectin ◽

Screening Tests ◽

Hematological Toxicity ◽

Therapeutic Drug ◽

Personalized Care

In the past, laboratory tests were considered of limited value in Crohn's disease (CD). In the era of biologics, laboratory tests have become essential to evaluate the inflammatory burden of the disease (C-reactive protein, fecal calprotectin) since symptoms-based scores are subjective, to predict the response to pharmacological options and the risk of relapse, to discriminate CD from ulcerative colitis, to select candidates to anti-tumor necrosis factors [screening tests looking for hepatitis B virus and hepatitis C virus status and latent tuberculosis], to assess the risk of adverse events (testing for thiopurine metabolites and thiopurine-methyltransferase activity), and to personalize and optimize therapy (therapeutic drug monitoring). Pharmacogenetics, though presently confined to the assessment of thiopurineme methyltransferase polymorphisms and hematological toxicity associated with thiopurine treatment, is a promising field that will contribute to a better understanding of the molecular mechanisms of the variability in response to the drugs used in CD with the attempt to expand personalized care and precision medicine strategies.

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FECAL CALPROTECTIN: levels for the ethiological diagnosis in Brazilian patients with gastrointestinal symptoms

Arquivos de Gastroenterologia ◽

10.1590/s0004-28032015000100011 ◽

2015 ◽

Vol 52 (1) ◽

pp. 50-54 ◽

Cited By ~ 8

Author(s):

Lorete Maria da Silva KOTZE ◽

Renato Mitsunori NISIHARA ◽

Sandra Beatriz MARION ◽

Murilo Franco CAVASSANI ◽

Paulo Gustavo KOTZE

Keyword(s):

Ulcerative Colitis ◽

Irritable Bowel Syndrome ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Inflammatory Bowel Diseases ◽

Fecal Calprotectin ◽

Bowel Diseases ◽

Inflammatory Bowel ◽

Irritable Bowel ◽

Active Disease

Background Determination of fecal calprotectin can provide an important guidance for the physician, also in primary care, in the differential diagnosis of gastrointestinal disorders, meanly between inflammatory bowel diseases and irritable bowel syndrome. Objectives The aims of the present study were to prospectively investigate, in Brazilian adults with gastrointestinal complaints, the value of fecal calprotectin as a biomarker for the differential diagnosis between functional and organic disorders and to correlate the concentrations with the activity of inflammatory bowel diseases. Methods The study included consecutive patients who had gastrointestinal complaints in which the measurement levels of fecal calprotectin were recommended. Fecal calprotectin was measured using a Bühlmann (Basel, Switzerland) ELISA kit Results A total of 279 patients were included in the study, with median age of 39 years (range, 18 to 78 years). After clinical and laboratorial evaluation and considering the final diagnosis, patients were allocated into the following groups: a) Irritable Bowel Syndrome: 154 patients (102 female and 52 male subjects). b) Inflammatory Bowel Diseases group: 112 patients; 73 with Crohn’s disease; 38 female and 35 male patients; 52.1% (38/73) presented active disease, and 47.9% (35/73) had disease in remission and 39 patients with ulcerative colitis;19 female and 20 male patients; 48.7% (19/39) classified with active disease and 49.3% (20/39) with disease in remission. A significant difference (P<0.001) was observed between the median value of fecal calprotectin in Irritable Bowel Syndrome group that was 50.5 µg/g (IQR=16 - 294 µg/g); 405 µg/g (IQR=29 - 1980 µg/g) in Crohn’s disease patients and 457 µg/g (IQR=25 - 1430 µg/g) in ulcerative colitis patients. No difference was observed between the values found in the patients with Crohn’s disease and ulcerative colitis. Levels of fecal calprotectin were significantly lower in patients with inflammatory bowel diseases in remission when compared with active disease (P<0.001). Conclusions The present study showed that the determination of fecal calprotectin assists to differentiate between active and inactive inflammatory bowel diseases and between inflammatory bowel diseases and irritable bowel syndrome.

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Fecal calprotectin and contrast enhanced transabdominal ultrasonography in assessment of Crohn's disease patients

Digestive and Liver Disease ◽

10.1016/s1590-8658(06)80032-0 ◽

2006 ◽

Vol 38 ◽

pp. S13-S14

Author(s):

F. Morace ◽

V. D'Angelo ◽

G. Amalfi ◽

M. Di Pierro ◽

C. Farinato ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Fecal Calprotectin ◽

Transabdominal Ultrasonography ◽

Contrast Enhanced

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Upper Gastrointestinal Crohn’s Disease: Literature Review and Case Presentation

Case Reports in Gastrointestinal Medicine ◽

10.1155/2019/2708909 ◽

2019 ◽

Vol 2019 ◽

pp. 1-5 ◽

Cited By ~ 1

Author(s):

Soorya N. Aggarwal ◽

Yana Cavanagh ◽

Lan Wang ◽

Amer Akmal ◽

Matthew A. Grossman

Keyword(s):

Crohn’S Disease ◽

Gastrointestinal Tract ◽

Iron Deficiency ◽

Crohn's Disease ◽

Fecal Calprotectin ◽

Upper Gastrointestinal Tract ◽

Laboratory Evaluation ◽

Deficiency Anemia ◽

Endoscopic Evaluation ◽

Upper Gastrointestinal

Upper gastrointestinal tract predominant Crohn’s Disease (CD) remains an elusive clinical entity, manifesting limited or vague symptomatology, eluding clinical suspicion, and delaying subsequent diagnostic evaluation. As a result, it has not been widely described and there is a lack of clear recommendations for diagnosis or management. Standard IBD evaluation including serologic testing, imaging, and endoscopy may initially not be fruitful. Furthermore, endoscopic evaluation may be grossly normal in patients without long standing-disease. We describe an 18-year-old male who presented with only unexplained, persistent iron-deficiency anemia. Extensive outpatient testing including multiple endoscopic evaluations with standard biopsies was unfruitful. Ultimately, a positive fecal calprotectin prompted enteroscopy with endoscopic mucosal resection (EMR) in an effort to obtain a larger, deeper tissue specimen. Grossly cobblestoned mucosa along with histopathology revealing focal crypt abscesses, chronic inflammation in the lamina propria, and superficial foveolar epithelial regenerative changes were consistent with CD. This patient’s case illustrates the need for a high degree of suspicion for CD in patients with unexplained or persistent iron deficiency anemias. Persistent investigation yielded an elevation in fecal calprotectin suggesting underlying gastrointestinal inflammation and prompted advanced endoscopic evaluation with EMR. Waxing and waning tissue findings are characteristic of CD and pose a unique challenge in patients with upper gastrointestinal predominant pathology. As such, diligent workup including laboratory evaluation, imaging, and serial endoscopy is critical to establish pathology and dictate subsequent management in IBD, especially upper gastrointestinal tract predominant CD.

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Sa1816 – Elevated Fecal Calprotectin in Healthy First Degree Relatives of Patients with Crohn's Disease is Associated with Future Diagnosis of Crohn's Disease

Gastroenterology ◽

10.1016/s0016-5085(19)37883-7 ◽

2019 ◽

Vol 156 (6) ◽

pp. S-413 ◽

Cited By ~ 2

Author(s):

Sun-Ho Lee ◽

Namita Power ◽

Williams Turpin ◽

Larbi Bedrani ◽

Juan Antonio Raygoza Garay ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Fecal Calprotectin ◽

First Degree Relatives

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The New Proactive Approach and Precision Medicine in Crohn’s Disease

Biomedicines ◽

10.3390/biomedicines8070193 ◽

2020 ◽

Vol 8 (7) ◽

pp. 193

Author(s):

Eran Zittan ◽

Ian M. Gralnek ◽

Marc S. Berns

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Personalized Medicine ◽

Precision Medicine ◽

Unmet Need ◽

Fecal Calprotectin ◽

Mucosal Inflammation ◽

Remission Induction ◽

Clinical Relapse ◽

Proactive Approach

The proactive approach to Crohn’s disease (CD) management advocates moving toward algorithmic tight-control scenarios that are designed for each CD phenotype to guide remission induction, maintenance therapy, active monitoring, and multidisciplinary care to manage the complexities of each inflammatory bowel disease (IBD) patient. This requires accurate initial clinical, laboratory, radiological, endoscopic, and/or tissue diagnosis for proper phenotypic stratification of each CD patient. A substantial proportion of patients in symptomatic remission have been reported to demonstrate evidence of active disease, with elevated fecal calprotectin(FC) and C-reactive protein (CRP) levels as a hallmark for mucosal inflammation. Active mucosal inflammation, and elevated CRP and fecal calprotectin (FC) have been shown to be good predictors of clinical relapse, disease progression, and complications in IBD patients. The next frontier of treatment is personalized medicine or precision medicine to help solve the problem of IBD heterogeneity and variable responses to treatment. Personalized medicine has the potential to increase the efficacy and/or reduce potential adverse effects of treatment for each CD phenotype. However, there is currently an unmet need for better elucidation of the inflammatory biopathways and genetic signatures of each IBD phenotype, so personalized medicine can specifically target the underlying cause of the disease and provide maximal efficacy to each patient.

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P319 Accurate cut-offs for predicting endoscopic activity and mucosal healing in Crohn's disease with fecal calprotectin

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjx002.444 ◽

2017 ◽

Vol 11 (suppl_1) ◽

pp. S239-S239 ◽

Cited By ~ 1

Author(s):

J.M. Vázquez-Morόn ◽

B. Benítez-Rodríguez ◽

H. Pallarés-Manrique ◽

F.H. Machancoses ◽

J.L. Robles Rodríguez ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Fecal Calprotectin ◽

Mucosal Healing

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Microbial Signature in Adipose Tissue of Crohn’s Disease Patients

Journal of Clinical Medicine ◽

10.3390/jcm9082448 ◽

2020 ◽

Vol 9 (8) ◽

pp. 2448

Author(s):

Carolina Serena ◽

Maribel Queipo-Ortuño ◽

Monica Millan ◽

Lidia Sanchez-Alcoholado ◽

Aleidis Caro ◽

...

Keyword(s):

Adipose Tissue ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Pathogenic Bacteria ◽

Sulfur Metabolism ◽

Clinical Status ◽

Subcutaneous Fat ◽

Intestinal Barrier ◽

Fecal Calprotectin ◽

Inactive Disease

Crohn’s disease (CD) is characterized by compromised immune tolerance to the intestinal commensal microbiota, intestinal barrier inflammation, and hyperplasia of creeping fat (CF) and mesenteric adipose tissue (AT), which seems to be directly related to disease activity. Gut microbiota dysbiosis might be a determining factor in CD etiology, manifesting as a low microbial diversity and a high abundance of potentially pathogenic bacteria. We tested the hypothesis that CF is a reservoir of bacteria through 16S-rRNA sequencing of several AT depots of patients with active and inactive disease and controls. We found a microbiome signature within CF and mesenteric AT from patients, but not in subcutaneous fat. We failed to detect bacterial DNA in any fat depot of controls. Proteobacteria was the most abundant phylum in both CF and mesenteric AT, and positively correlated with fecal calprotectin/C-reactive protein. Notably, the clinical status of patients seemed to be related to the microbiome signature, as those with the inactive disease showed a reduction in the abundance of pathogenic bacteria. Predictive functional profiling revealed many metabolic pathways including lipopolysaccharide biosynthesis and sulfur metabolism overrepresented in active CD relative to that in inactive CD. Our findings demonstrate that microbiota dysbiosis associated with CD pathophysiology is reflected in AT and might contribute to disease severity.

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