Assessment of Histologic Disease Activity in Crohnʼs Disease

Mojtahed, Amirkaveh; Khanna, Reena; Sandborn, William J.; D’Haens, Geert; Feagan, Brian G.; Shackelton, Lisa M.; Baker, Kenneth A; Dubcenco, Elena; Valasek, Mark A.; Geboes, Karel; Levesque, Barrett G.

doi:10.1097/mib.0000000000000155

Cited by 45 publications

(28 citation statements)

References 56 publications

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“…Principal coordinate analysis (PCoA) based on the species-level Bray-Curtis [19] dissimilarity revealed overlap between the ME/CFS and control subjects (Fig. 2b).…”

Section: Resultsmentioning

confidence: 99%

Fecal metagenomic profiles in subgroups of patients with myalgic encephalomyelitis/chronic fatigue syndrome

et al. 2017

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BackgroundMyalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is characterized by unexplained persistent fatigue, commonly accompanied by cognitive dysfunction, sleeping disturbances, orthostatic intolerance, fever, lymphadenopathy, and irritable bowel syndrome (IBS). The extent to which the gastrointestinal microbiome and peripheral inflammation are associated with ME/CFS remains unclear. We pursued rigorous clinical characterization, fecal bacterial metagenomics, and plasma immune molecule analyses in 50 ME/CFS patients and 50 healthy controls frequency-matched for age, sex, race/ethnicity, geographic site, and season of sampling.ResultsTopological analysis revealed associations between IBS co-morbidity, body mass index, fecal bacterial composition, and bacterial metabolic pathways but not plasma immune molecules. IBS co-morbidity was the strongest driving factor in the separation of topological networks based on bacterial profiles and metabolic pathways. Predictive selection models based on bacterial profiles supported findings from topological analyses indicating that ME/CFS subgroups, defined by IBS status, could be distinguished from control subjects with high predictive accuracy. Bacterial taxa predictive of ME/CFS patients with IBS were distinct from taxa associated with ME/CFS patients without IBS. Increased abundance of unclassified Alistipes and decreased Faecalibacterium emerged as the top biomarkers of ME/CFS with IBS; while increased unclassified Bacteroides abundance and decreased Bacteroides vulgatus were the top biomarkers of ME/CFS without IBS. Despite findings of differences in bacterial taxa and metabolic pathways defining ME/CFS subgroups, decreased metabolic pathways associated with unsaturated fatty acid biosynthesis and increased atrazine degradation pathways were independent of IBS co-morbidity. Increased vitamin B6 biosynthesis/salvage and pyrimidine ribonucleoside degradation were the top metabolic pathways in ME/CFS without IBS as well as in the total ME/CFS cohort. In ME/CFS subgroups, symptom severity measures including pain, fatigue, and reduced motivation were correlated with the abundance of distinct bacterial taxa and metabolic pathways.ConclusionsIndependent of IBS, ME/CFS is associated with dysbiosis and distinct bacterial metabolic disturbances that may influence disease severity. However, our findings indicate that dysbiotic features that are uniquely ME/CFS-associated may be masked by disturbances arising from the high prevalence of IBS co-morbidity in ME/CFS. These insights may enable more accurate diagnosis and lead to insights that inform the development of specific therapeutic strategies in ME/CFS subgroups.Electronic supplementary materialThe online version of this article (doi:10.1186/s40168-017-0261-y) contains supplementary material, which is available to authorized users.

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“…Principal coordinate analysis (PCoA) based on the species-level Bray-Curtis [19] dissimilarity revealed overlap between the ME/CFS and control subjects (Fig. 2b).…”

Section: Resultsmentioning

confidence: 99%

Fecal metagenomic profiles in subgroups of patients with myalgic encephalomyelitis/chronic fatigue syndrome

et al. 2017

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“…Accordingly, endoscopic remission, defined as resolution of ulcers at ileocolonoscopy has been proposed as a treatment target in the Selecting Therapeutic in Inflammatory Bowel Disease (STRIDE) consensus recommendations . However, persistent histological inflammation is present in up to one‐third of biopsies from Crohn's disease patients with endoscopically healed mucosa . Thus, a key question is whether endoscopic remission is sufficient to prevent disease relapse and future complications, or whether histological remission should additionally be used to define mucosal healing …”

Section: Introductionmentioning

confidence: 99%

“…To determine the potential value of histology in Crohn's disease management and assessment of response to therapy, endoscopic mucosal biopsies must be collected in a consistent and reproducible manner. Definition of an optimal biopsy location is confounded by the patchy nature of Crohn's disease, in which regions of normal‐appearing mucosa alternate between areas of inflammation and ulcers . The need for standardisation of biopsy procurement has been emphasised in the literature and is especially important during drug development to optimally define response to therapy, as demonstrated by recent clinical trials in Crohn's disease .…”

Section: Introductionmentioning

confidence: 99%

Evaluation of optimal biopsy location for assessment of histological activity, transcriptomic and immunohistochemical analyses in patients with active Crohn’s disease

Novak

Stevens

Viegen

et al. 2019

Aliment Pharmacol Ther

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Background:The appropriate location for biopsy procurement relative to an ulcer in active Crohn's disease is unknown.Aim: To explore the relationship between biopsy location, histological disease activity, proinflammatory gene expression and the presence of inflammatory cells.Methods: Fifty-one patients with Crohn's disease and ulcers >0.5 cm diameter in the colon and/or ileum were prospectively enrolled at three centres. Biopsies were obtained from 0 mm, 7 to 8 mm and 21 to 24 mm from the edge of the largest ulcer.Histological activity was blindly assessed with the Global Histological Disease Activity Score, the Robarts Histopathology and Nancy Histological indices. Messenger ribonucleic acid (mRNA) levels for interleukins-6, -8 and -23 (p19 and p40 subunits), CD31 and S100A9 were measured using quantitative polymerase chain reaction. The number of CD3+, CD68+ and myeloperoxidase-positive cells was quantified by immunohistochemistry. Data were analysed using mixed models with location and segment as fixed effects and patients as random effect to account for correlation among segments within a patient.Results: Histological disease activity scores (P < 0.0001), proinflammatory gene expression levels (P < 0.005) and numbers of myeloperoxidase-positive cells (P < 0.0001) were highest in biopsies from the ulcer edge in the colon and ileum, with decreasing gradients observed with distance from the edge (P < 0.05). No differences between colonic and ileal samples were detected for the parameters measured at any location. Conclusions:Biopsies from the ulcer edge in patients with Crohn's disease yielded the greatest histological disease activity and mRNA levels and had similar readouts in the colon and ileum. Research is needed to confirm this conclusion for other measures.

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“…The latter is defined as endoscopic remission and complete resolution of microscopic inflammation on biopsy [23]. Although clinical experience with these new definitions is limited [24][25][26], their use in clinical trials has stimulated a shift in treatment algorithms with more emphasis being placed on reaching goals of therapy that can prevent long-term complications [5,6].…”

Section: Introductionmentioning

confidence: 99%

Combination therapy for the treatment of Crohn’s disease

Mosli

Feagan

2015

Expert Opinion on Biological Therapy

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Assessment of Histologic Disease Activity in Crohnʼs Disease

Abstract: Measurement of histologic disease activity has potential value in CD; however, no validated measures are available. Additional research is needed to develop a methodologically rigorous instrument for use in clinical investigation and potentially for clinical practice.

Cited by 45 publications

References 56 publications

Fecal metagenomic profiles in subgroups of patients with myalgic encephalomyelitis/chronic fatigue syndrome

Fecal metagenomic profiles in subgroups of patients with myalgic encephalomyelitis/chronic fatigue syndrome

Evaluation of optimal biopsy location for assessment of histological activity, transcriptomic and immunohistochemical analyses in patients with active Crohn’s disease

Combination therapy for the treatment of Crohn’s disease

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