Associations of NOD2 polymorphisms with Erysipelotrichaceae in stool of in healthy first degree relatives of Crohn's disease subjects.

BACKGROUND: Genetic analyses have identified many variants associated with the risk of inflammatory bowel disease (IBD) development. Among these variants, the ones located within the NOD2 gene have the highest odds ratio of all IBD genetic risk variants. Also, patients with Crohn's disease (CD) have been shown to have an altered gut microbiome, which might be a reflection of inflammation itself or an effect of other parameters that contribute to the risk of the disease. Since NOD2 is an intracellular pattern recognition receptor that senses bacterial peptidoglycan in the cytosol and stimulates the host immune response (Al Nabhani et al., PLoS Pathog 13:e1006177, 2017), it is hypothesized that NOD2 variants represent perfect candidates for influencing host-microbiome interactions. We hypothesized that NOD2 risk variants affect the microbiome composition of healthy first degree relative (FDR) of CD patients and thus potentially contribute to an altered microbiome state before disease onset. METHODS: Based on this, we studied a large cohort of 1546 healthy FDR of CD patients and performed a focused analysis of the association of three major CD SNPs in the coding region of the NOD2 gene, which are known to confer a 15-40-fold increased risk of developing CD in homozygous or compound heterozygous individuals. RESULTS: Our results show that carriers of the C allele at rs2066845 was significantly associated with an increase in relative abundance in the fecal bacterial family Erysipelotrichaceae. CONCLUSIONS: This result suggests that NOD2 polymorphisms contribute to fecal microbiome composition in asymptomatic individuals. Whether this modulation of the microbiome influences the future development of CD remains to be assessed.

Associations between quantitative evaluation of bowel wall microvascular flow by contrast-enhanced ultrasound and indices of disease activity in Crohn's disease patients using both bolus and infusion techniques.

PURPOSE: The aim is to investigate whether baseline contrast-enhanced ultrasound (CEUS) correlates with indices of activity in Crohn's disease (CD) and can predict response to medical treatment. METHODS: In this prospective study, symptomatic CD patients underwent baseline CEUS performed with Definity using both bolus and infusion methods. Time-intensity curves (TIC), peak intensity (PI), and area under curve (AUC) from a region of interest over the diseased bowel were calculated for both bolus and infusion acquisitions. We used Mann-Whitney U test for continuous and chi-square/two-tailed Fisher's exact test for categorical variable comparison and Spearman's correlation coefficient to correlate clinical score and CEUS kinetic parameters. RESULTS: Twenty-one patients (9 men, 12 women, median age 32 years) were accrued. Fifteen patients had clinically active disease defined as Harvey-Bradshaw Index (HBI) score ≥5. Median values of baseline CEUS parameters PI (bolus: 26 vs 8.86; P = .023 and perfusion: 7.6 vs 3.2; P = .009) and AUC (bolus: 769 vs 248.8; P = .036 and perfusion: 188.9 vs 73.9; P = .012) differed significantly in patients with active vs inactive disease. Nine patients with active disease underwent escalated or new treatment. Five were nonresponders. Responders had higher median values of baseline parameters (PI, bolus: 35 vs 18.8; P = .556, and perfusion: 7.6 vs 3.9; P = 190), (AUC, bolus: 1473.9 vs 314; P = .111, and perfusion: 154.7 vs 74.4, P = .286). CONCLUSIONS: CEUS kinetic parameters correlate with clinical and laboratory indices and are significantly higher in patients with active disease. The responders had higher CEUS kinetic parameters than nonresponders that did not reach statistical significance in our small cohort.

Evaluation of Stool frequency and stool form as measures of HIV-related diarrhea.

PURPOSE: In the highly active antiretroviral therapy (HAART) era, HIV-related diarrhea remains common. Our aim was to evaluate stool frequency and form as measures of HIV-related diarrhea. METHOD: Forty-eight HIV-infected persons with self-reported diarrhea were studied. In Analysis 1, self-reported retrospective and 7-day prospective measurement of stool frequency and form were compared using Spearman's correlation coefficient. In Analysis 2, diarrhea was measured during two 8-hour study periods in a subgroup (n = 20) using stool weight (Wt), diarrhea symptom score (Sx Score), stool frequency (SP-freq), and stool form using the Bristol Stool Form Scale (SP-BSFS). SP-freq and SP-BSFS were modeled alone and in combination to predict Wt and Sx Score. RESULTS: In Analysis 1, correlation between measures of stool frequency was rs = 0.62 (p < .0001) but was rs = 0.16 (p = .26) between measures of stool form. In Analysis 2, the two-predictor model best predicted Wt, whereas the model using SP-freq only performed as well as the two-predictor model to predict Sx Score. CONCLUSION: Prospective measurement of stool frequency performed well; in some situations, it may be used alone to measure severity of HIV-related diarrhea. Our findings may be used to design more rigorous clinical trials in HIV.

Systematic review of strategies to measure HIV-related diarrhea.

INTRODUCTION: In the highly active antiretroviral therapy (HAART) era, HIV-related diarrhea remains common. There is no gold standard to measure diarrhea, making comparison across trials difficult. We conducted a systematic review to determine current research practice in measuring HIV-related diarrhea. METHOD: MEDLINE was searched from 1980 to 2006 for clinical trials of treatment for HIV-related diarrhea. The following data were abstracted: type of trial, treatment studied, definition of diarrhea, and definition of improvement in diarrhea. RESULTS: We reviewed 384 articles; 46 met our inclusion criteria. Forty-two trials were prospective: 25 were open-label and 17 were controlled trials. Antimicrobials were studied most often (15 trials): octreotide was studied in 10 trials, and HAART in 5. Presence of diarrhea was most often defined by duration (33 trials, 72%), stool frequency (29 trials, 63%), and/or stool form (23 trials, 50%); often, more than one parameter was used. Stool frequency was used most often to measure diarrhea improvement (28 trials, 61%). Only one trial used a measure validated for HIV-related diarrhea. CONCLUSION: Investigators rely on non-validated and disparate measures of HIV-related diarrhea. An easy-to-use, well-accepted, and valid tool to measure HIV-related diarrhea would enhance research in this field.