The Role of MR Enterography in Assessing Crohn’s Disease Activity and Treatment Response

MR enterography (MRE) has become the primary imaging modality in the assessment of Crohn’s disease (CD) in both children and adults at many institutions in the United States and worldwide, primarily due to its noninvasiveness, superior soft tissue contrast, and lack of ionizing radiation. MRE technique includes distention of the small bowel with oral contrast media with the acquisition of T2-weighted, balanced steady-state free precession, and multiphase T1-weighted fat suppressed gadolinium contrast-enhanced sequences. With the introduction of molecule-targeted biologic agents into the clinical setting for CD and their potential to reverse the inflammatory process, MRE is increasingly utilized to evaluate disease activity and response to therapy as an imaging complement to clinical indices or optical endoscopy. New and emerging MRE techniques, such as diffusion-weighted imaging (DWI), magnetization transfer, ultrasmall superparamagnetic iron oxide- (USPIO-) enhanced MRI, and PET-MR, offer the potential for an expanded role of MRI in detecting occult disease activity, evaluating early treatment response/resistance, and differentiating inflammatory from fibrotic strictures. Familiarity with MR enterography is essential for radiologists and gastroenterologists as the technique evolves and is further incorporated into the clinical management of CD

Avoidant Restrictive Food Intake Disorder Prevalent Among Patients With Inflammatory Bowel Disease

Background & Aims Inflammatory bowel disease (IBD) patients alter their dietary behaviors to reduce disease-related symptoms, avoid feared food triggers, and control inflammation. This study aimed to estimate the prevalence of avoidant/restrictive food intake disorder (ARFID), evaluate risk factors, and examine the association with risk of malnutrition in patients with IBD. Methods This cross-sectional study recruited adult patients with IBD from an ambulatory clinic. ARFID risk was measured using the Nine-Item ARFID Screen. Nutritional risk was measured with the Patient Generated-Subjective Global Assessment. Logistic regression models were used to evaluate the association between clinical characteristics and a positive ARFID risk screen. Patient demographics, disease characteristics, and medical history were abstracted from medical records. Results Of the 161 participants (Crohn’s disease, 45.3%; ulcerative colitis, 51.6%; IBD-unclassified, 3.1%), 28 (17%) had a positive ARFID risk score (≥24). Most participants (92%) reported avoiding 1 or more foods while having active symptoms, and 74% continued to avoid 1 or more foods even in the absence of symptoms. Active symptoms (odds ratio, 5.35; 95% confidence interval, 1.91–15.01) and inflammation (odds ratio, 3.31; 95% confidence interval, 1.06–10.29) were significantly associated with positive ARFID risk. Patients with a positive ARFID risk screen were significantly more likely to be at risk for malnutrition (60.7% vs 15.8%; P \u3c .01). Conclusions Avoidant eating behaviors are common in IBD patients, even when in clinical remission. Patients who exhibit active symptoms and/or inflammation should be screened for ARFID risk, with referrals to registered dietitians to help monitor and address disordered eating behaviors and malnutrition risk

Inflammation and glucose intolerance. A prospective study of gestational diabetes mellitus

WSTĘP. Podwyższony poziom leukocytów w surowicy krwi jest wskaźnikiem procesu zapalenia, który, jak wykazują badania prospektywne, wiąże się z rozwojem cukrzycy typu 2. Chociaż cukrzyca ciążowa oraz cukrzyca typu 2 mają dużo wspólnych mechanizmów patofizjologicznych, w niewielu pracach badano związek zapalenia z rozwojem cukrzycy ciążowej. MATERIAŁ I METODY. W badaniu oceniano w sposób prospektywny liczbę leukocytów w próbkach krwi pobranych podczas pierwszej rutynowej wizyty kontrolnej w grupie 2753 kobiet w ciąży &#8212; wieloródek z prawidłową wartością glikemii. U 98 (3,6%) z nich wystąpiła później cukrzyca ciążowa. Pacjentki podzielono na podgrupy w zależności od kwartyla liczby leukocytów i porównano wyniki przeprowadzanego w trzecim trymestrze przesiewowego testu tolerancji glukozy oraz częstość cukrzycy ciążowej wśród kobiet należących do poszczególnych kwartyli. Zastosowano test regresji logistycznej, aby obliczyć skorygowane względem jednego i wielu czynników względne ryzyko wystąpienia cukrzycy ciążowej w zależności od kwartyla leukocytozy. WYNIKI. U kobiet, u których doszło do rozwoju cukrzycy ciążowej, stężenie leukocytów w surowicy krwi było wyższe (10,5 &plusmn; 2,2 vs. 9,2 &plusmn; 2,2 × 103 komórek/ml; p < 0,01) niż u pacjentek, u których metabolizm węglowodanów pozostał prawidłowy. Wraz ze wzrostem kwartyla leukocytozy obserwowano liniowy wzrost glikemii po obciążeniu glukozą (p < 0,01), pola pod krzywą testu tolerancji glukozy (p < 0,01) oraz częstości cukrzycy ciążowej (kwartyl 1. &#8212; 1,1%; kwartyl 2. &#8212; 2,5%; kwartyl 3. &#8212; 4,2% i kwartyl 4. &#8212; 6,4%; p < 0,01). W analizie wieloczynnikowej, wraz ze wzrostem kwartyla leukocytozy, liniowy trend względnego ryzyka (RR, relative risk) rozwoju cukrzycy ciążowej pozostał statystycznie istotny [kwartyl 1. &#8212; referencyjny, kwartyl 2. &#8212; RR 2,3 (95% CI 0,9-5,7), kwartyl 3. &#8212; RR 3,3 (1,4&#8211;7,8), kwartyl 4. &#8212; RR 4,9 (2,1&#8211;11,2); p < 0,01]. WNIOSKI. Podwyższony poziom leukocytów we wczesnym okresie ciąży jest w sposób niezależny, liniowy związany z wynikami testów przesiewowych w kierunku cukrzycy ciążowej oraz ryzykiem wystąpienia tej choroby. Brak wyraźnej granicy w rozkładzie liczby leukocytów sprawia, że wskaźnik ten nie może mieć zastosowania klinicznego, chociaż dane sugerują, że proces zapalenia wiąże się z rozwojem cukrzycy ciążowej. Może to być kolejny mechanizm patofizjologiczny, łączący występowanie cukrzycy ciążowej z rozwojem w przyszłości cukrzycy typu 2.INTRODUCTION. Increased leukocyte count is a marker of inflammation that has been associated with the development of type 2 diabetes in prospective studies. Although gestational diabetes mellitus (GDM) and type 2 diabetes share certain pathophysiological mechanisms, few studies have examined inflammation and risk of GDM. MATERIAL AND METHODS. We prospectively examined routine leukocyte counts collected at the first prenatal visit in a cohort of 2,753 nulliparous euglycemic women, 98 (3.6%) of whom were later diagnosed with GDM. Subjects were divided into quartiles of leukocyte count, and the results of third-trimester glucose screening tests and the incidence of GDM among these quartiles were compared. Logistic regression was used to calculate univariate and multivariable-adjusted relative risks (RRs) of GDM according to leukocyte quartiles. RESULTS. Leukocyte counts were increased among women who subsequently developed GDM compared with those who remained free of GDM (10.5 &#177; &#177; 2.2 vs. 9.2 &#177; 2.2 × 103 cells/ml; P < 0.01). There was a linear increase in postloading mean glucose levels (P for trend < 0.01), the area under the glucose tolerance test curves (P for trend < 0.01), and the incidence of GDM (quartile 1, 1.1; quartile 2, 2.5; quartile 3, 4.2; and quartile 4, 6.4%; P for trend < 0.01) with increasing leukocyte quartiles. In the multivariable-adjusted analysis, the linear trend in the RR of GDM with increasing leukocyte quartiles remained statistically significant (quartile 1, reference; quartile 2, RR 2.3 [95% CI 0.9&#8211;5.7]; quartile 3, 3.3 [1.4&#8211;7.8]; quartile 4, 4.9 [2.1&#8211;11.2]; P for trend < 0.01). CONCLUSIONS. Increased leukocyte count early in pregnancy is independently and linearly associated with the results of GDM screening tests and the risk of GDM. Although overlap in the leukocyte count distributions precludes it from being a clinically useful biomarker, these data suggest that inflammation is associated with the development of GDM and may be another pathophysiological link between GDM and future type 2 diabetes

Tethered capsule endomicroscopy enables less-invasive imaging of gastrointestinal tract microstructure

Here, we introduce “tethered capsule endomicroscopy,” that involves swallowing an optomechanically-engineered pill that captures cross-sectional, 30 μm (lateral) × 7 μm (axial) resolution, microscopic images of the gut wall as it travels through the digestive tract. Results in human subjects show that this technique rapidly provides three-dimensional, microstructural images of the upper gastrointestinal tract in a simple and painless procedure, opening up new opportunities for screening for internal diseases

Early life environment and natural history of inflammatory bowel diseases

Background: Early life exposures may modify risk of inflammatory bowel diseases (IBD; Crohn’s disease (CD), ulcerative colitis (UC)). However, the relationship between early life exposures and natural history of IBD has not been previously examined. Methods: This single center study included patients with CD or UC recruited in a prospective IBD registry. Enrolled patients completed a detailed environmental questionnaire that assessed various early life environmental exposures. Our primary outcome was requirement for disease-related surgery in CD and UC. Logistic regression models defined independent effect of early life exposures, adjusting for potential confounders. Results: Our study included 333 CD and 270 UC patients. Just over half were female with a median age at diagnosis of 25 years. One-third of the cohort had history of bowel surgery (31%) and nearly half had used at least one biologic agent (47%). Among those with CD, being breastfed was associated with reduced risk of CD-related surgery (34% vs. 55%), while childhood cigarette smoke exposure was associated with increased risk. On multivariate analysis, history of being breastfed (odds ratio (OR) 0.21, 95% confidence interval [CI] 0.09–0.46) and cigarette smoke exposure as a child (OR 2.17, 95% CI 1.10–4.29) remained independently associated with surgery. None of the early life variables influenced disease phenotype or outcome in UC. Conclusion: A history of being breastfed was associated with a decreased risk while childhood cigarette smoke exposure was associated with an increased risk of surgery in patients with CD. Further investigation to examine biological mechanisms is warranted. Electronic supplementary material The online version of this article (doi:10.1186/s12876-014-0216-8) contains supplementary material, which is available to authorized users

Multi-omics of the gut microbial ecosystem in inflammatory bowel diseases.

Inflammatory bowel diseases, which include Crohn's disease and ulcerative colitis, affect several million individuals worldwide. Crohn's disease and ulcerative colitis are complex diseases that are heterogeneous at the clinical, immunological, molecular, genetic, and microbial levels. Individual contributing factors have been the focus of extensive research. As part of the Integrative Human Microbiome Project (HMP2 or iHMP), we followed 132 subjects for one year each to generate integrated longitudinal molecular profiles of host and microbial activity during disease (up to 24 time points each; in total 2,965 stool, biopsy, and blood specimens). Here we present the results, which provide a comprehensive view of functional dysbiosis in the gut microbiome during inflammatory bowel disease activity. We demonstrate a characteristic increase in facultative anaerobes at the expense of obligate anaerobes, as well as molecular disruptions in microbial transcription (for example, among clostridia), metabolite pools (acylcarnitines, bile acids, and short-chain fatty acids), and levels of antibodies in host serum. Periods of disease activity were also marked by increases in temporal variability, with characteristic taxonomic, functional, and biochemical shifts. Finally, integrative analysis identified microbial, biochemical, and host factors central to this dysregulation. The study's infrastructure resources, results, and data, which are available through the Inflammatory Bowel Disease Multi'omics Database ( http://ibdmdb.org ), provide the most comprehensive description to date of host and microbial activities in inflammatory bowel diseases

Complex host genetics influence the microbiome in inflammatory bowel disease

Background: Human genetics and host-associated microbial communities have been associated independently with a wide range of chronic diseases. One of the strongest associations in each case is inflammatory bowel disease (IBD), but disease risk cannot be explained fully by either factor individually. Recent findings point to interactions between host genetics and microbial exposures as important contributors to disease risk in IBD. These include evidence of the partial heritability of the gut microbiota and the conferral of gut mucosal inflammation by microbiome transplant even when the dysbiosis was initially genetically derived. Although there have been several tests for association of individual genetic loci with bacterial taxa, there has been no direct comparison of complex genome-microbiome associations in large cohorts of patients with an immunity-related disease. Methods: We obtained 16S ribosomal RNA (rRNA) gene sequences from intestinal biopsies as well as host genotype via Immunochip in three independent cohorts totaling 474 individuals. We tested for correlation between relative abundance of bacterial taxa and number of minor alleles at known IBD risk loci, including fine mapping of multiple risk alleles in the Nucleotide-binding oligomerization domain-containing protein 2 (NOD2) gene exon. We identified host polymorphisms whose associations with bacterial taxa were conserved across two or more cohorts, and we tested related genes for enrichment of host functional pathways. Results: We identified and confirmed in two cohorts a significant association between NOD2 risk allele count and increased relative abundance of Enterobacteriaceae, with directionality of the effect conserved in the third cohort. Forty-eight additional IBD-related SNPs have directionality of their associations with bacterial taxa significantly conserved across two or three cohorts, implicating genes enriched for regulation of innate immune response, the JAK-STAT cascade, and other immunity-related pathways. Conclusions: These results suggest complex interactions between genetically altered host functional pathways and the structure of the microbiome. Our findings demonstrate the ability to uncover novel associations from paired genome-microbiome data, and they suggest a complex link between host genetics and microbial dysbiosis in subjects with IBD across independent cohorts. Electronic supplementary material The online version of this article (doi:10.1186/s13073-014-0107-1) contains supplementary material, which is available to authorized users

Comprehensive confocal endomicroscopy of the esophagus in vivo

Background and study aims: Biopsy sampling error can be a problem for the diagnosis of certain gastrointestinal tract diseases. Spectrally-encoded confocal microscopy (SECM) is a high-speed reflectance confocal microscopy technology that has the potential to overcome sampling error by imaging large regions of gastrointestinal tract tissues. The aim of this study was to test a recently developed SECM endoscopic probe for comprehensively imaging large segments of the esophagus at the microscopic level in vivo. Methods: Topical acetic acid was endoscopically applied to the esophagus of a normal living swine. The 7 mm diameter SECM endoscopic probe was transorally introduced into the esophagus over a wire. Optics within the SECM probe were helically scanned over a 5 cm length of the esophagus. Confocal microscopy data was displayed and stored in real time. Results: Very large confocal microscopy images (length = 5 cm; circumference = 2.2 cm) of swine esophagus from three imaging depths, spanning a total area of 33 cm2, were obtained in about 2 minutes. SECM images enabled the visualization of cellular morphology of the swine esophagus, including stratified squamous cell nuclei, basal cells, and collagen within the lamina propria. Conclusions: The results from this study suggest that the SECM technology can rapidly provide large, contiguous confocal microscopy images of the esophagus in vivo. When applied to human subjects, the unique comprehensive, microscopic imaging capabilities of this technology may be utilized for improving the screening and surveillance of various esophageal diseases

A novel Ruminococcus gnavus clade enriched in inflammatory bowel disease patients

Background: Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the gastrointestinal tract that is associated with changes in the gut microbiome. Here, we sought to identify strain-specific functional correlates with IBD outcomes. Methods: We performed metagenomic sequencing of monthly stool samples from 20 IBD patients and 12 controls (266 total samples). These were taxonomically profiled with MetaPhlAn2 and functionally profiled using HUMAnN2. Differentially abundant species were identified using MaAsLin and strain-specific pangenome haplotypes were analyzed using PanPhlAn. Results: We found a significantly higher abundance in patients of facultative anaerobes that can tolerate the increased oxidative stress of the IBD gut. We also detected dramatic, yet transient, blooms of Ruminococcus gnavus in IBD patients, often co-occurring with increased disease activity. We identified two distinct clades of R. gnavus strains, one of which is enriched in IBD patients. To study functional differences between these two clades, we augmented the R. gnavus pangenome by sequencing nine isolates from IBD patients. We identified 199 IBD-specific, strain-specific genes involved in oxidative stress responses, adhesion, iron-acquisition, and mucus utilization, potentially conferring an adaptive advantage for this R. gnavus clade in the IBD gut. Conclusions: This study adds further evidence to the hypothesis that increased oxidative stress may be a major factor shaping the dysbiosis of the microbiome observed in IBD and suggests that R. gnavus may be an important member of the altered gut community in IBD. Electronic supplementary material The online version of this article (doi:10.1186/s13073-017-0490-5) contains supplementary material, which is available to authorized users