Diet-omics in the Study of Urban and Rural Crohn disease Evolution (SOURCE) cohort.

Crohn disease (CD) burden has increased with globalization/urbanization, and the rapid rise is attributed to environmental changes rather than genetic drift. The Study Of Urban and Rural CD Evolution (SOURCE, n = 380) has considered diet-omics domains simultaneously to detect complex interactions and identify potential beneficial and pathogenic factors linked with rural-urban transition and CD. We characterize exposures, diet, ileal transcriptomics, metabolomics, and microbiome in newly diagnosed CD patients and controls in rural and urban China and Israel. We show that time spent by rural residents in urban environments is linked with changes in gut microbial composition and metabolomics, which mirror those seen in CD. Ileal transcriptomics highlights personal metabolic and immune gene expression modules, that are directly linked to potential protective dietary exposures (coffee, manganese, vitamin D), fecal metabolites, and the microbiome. Bacteria-associated metabolites are primarily linked with host immune modules, whereas diet-linked metabolites are associated with host epithelial metabolic functions.

Change in bowel habits during menstruation: are IBD patients different?

BACKGROUND AND AIM: Many female inflammatory bowel disease (IBD) patients report symptoms exacerbation before and during menses. Our aim was to characterize their symptoms and specific risk factors in comparison with healthy controls. METHODS: Female IBD patients aged 18-50 years were asked to fill out a questionnaire recording their demographic and disease characteristics, menstruation history and symptoms. Disease activity was defined by Harvey-Bradshaw index (HBI) for Crohn's disease (CD) patients and modified mayo score for ulcerative colitis (UC) patients. Healthcare providers answering an internet survey assessing bowel symptoms during menstruation served as healthy controls. RESULTS: A total of 139 IBD patients, of whom 100 were CD patients, filled the questionnaire. The mean age was 30.4 [±7.7 standard deviation (SD)], mean disease duration was 7.8 (±6 SD), mean HBI was 4.7 (±3.8 SD), and mean Mayo score was 2.1 (±2.5 SD). A change in bowel habits during menstruation was reported by 72% of CD patients compared with 56% of UC patients (p = 0.07). Out of 258 healthy controls, 93% reported a change in bowel habits during menstruation compared with 68% of IBD patients (p < 0.001). However, other abdominal and constitutional symptoms were significantly more prevalent among IBD patients compared with healthy controls (p < 0.01 for most parameters). Smoking status, biologic treatment, and previous abdominal operation were found to significantly aggravate symptoms during menses in IBD patients. CONCLUSION: IBD patients experience various symptoms during menses significantly more commonly than healthy women. Smoking, biologic treatment, and previous abdominal operations are risk factors for higher symptomatic burden. Following future validation and research, these results can help in patients' risk stratification and possibly in risk reduction.

Lower adalimumab trough levels are associated with higher bowel wall thickness in Crohn's disease.

BACKGROUND: In Crohn's disease, higher adalimumab trough levels and negative anti-adalimumab-antibodies associate with better clinical and endoscopic outcomes. Intestinal ultrasound has become a relevant non-invasive method to monitor treatment. However, data on the association between adalimumab levels and bowel wall thickness measured with ultrasound is limited. OBJECTIVE: The purpose of this study was to examine the possible association between the sonographic transmural-thickness and adalimumab trough levels. METHODS: This prospective observational cohort study was conducted at Sheba Medical Center in 2014-2018. Crohn's disease patients on adalimumab maintenance therapy with intestinal ultrasound performed within <30 days of trough level measurement were included. Associations between terminal ileum and colonic thickness, adalimumab levels and therapy retention were assessed. RESULTS: Fifty events of ultrasound with concomitant adalimumab trough level measurements in 44 Crohn's disease patients were included. Patients with trough level <3 µg/ml had significantly higher bowel wall thickness, both for terminal ileum (p = 0.04) and colon (p = 0.02). Thirty-two patients continued adalimumab therapy over one year. The adalimumab retention rate was higher among those with terminal ileum thickness <4 mm (p = 0.03). CONCLUSION: Lower adalimumab trough levels were associated with higher bowel wall thickness indicating poorer therapy outcome. Transmural thickness measurement with ultrasound may be a useful target for guiding biologic therapy in Crohn's disease.

N-Acetyl-L-Cysteine inhibits the development of glucose intolerance and hepatic steatosis in diabetes-prone mice.

Oxidative stress is associated with different pathological conditions, including glucose intolerance and type 2 diabetes (T2D), however studies had failed to prove the benefits of antioxidants in T2D. AIM: On the assumption that the failure to demonstrate such anti-diabetic effects is a result of sub-optimal or excessive antioxidant dosage, we aimed to clarify the dose-response effect of the antioxidant N-Acetyl-L-Cysteine (NAC) on the progression of T2D in-vivo. METHODS: Experiments were conducted on KK-Ay mice and HFD-fed mice given NAC at different concentrations (200-1800 and 60-600 mg/kg/day, respectively). Glucose and insulin tolerance tests were performed and plasma insulin and lipid peroxidation were measured. Insulin signaling pathway was followed in muscle and liver. Hepatic TG accumulation and mRNA expression of genes involved in glucose metabolism were measured. RESULTS: While 600-1800 mg/kg/day NAC all improved glucose tolerance in KK-Ay mice, only the 1200 mg/kg/day treatment increased insulin sensitivity. Hepatic function was not affected, however; microsteatosis rather than macrosteatosis was observed in NAC-treated mice compared to control. Glucose tolerance was improved in NAC-treated HFD-fed mice as well; the best results obtained with a dose of 400 mg NAC/kg/day. This was followed by lower weight gain and hepatic TG. Plasma lipid peroxidation was not correlated with the glucose-lowering effects of NAC in either model. CONCLUSION: Identification of the optimal dose of NAC and the population that would benefit the most from such intervention is essential in order to apply preventive and/or therapeutic use of NAC and similar agents in the future.