Prebiotic fructans have greater impact on luminal microbiology and CD3+ T cells in healthy siblings than patients with Crohn’s disease : a pilot study investigating the potential for primary prevention of inflammatory bowel disease

Funding This work was supported by a clinical research fellowship granted by the charity Core (Guts UK) (CRH). FMF and PL received financial support from the Scottish Government Rural and Environment Science and Analytical Services. Acknowledgments The authors would like to acknowledge BENEO-Orafti, Teinen, Belgium who provided the oligofructose-enriched inulin. The authors would like to thank the patients and the siblings who generously participated in this study.Peer reviewedPostprin

Dietary intake of inulin-type fructans in active and inactive Crohn’s disease and healthy controls: a case-control study

Background and Aims: Prebiotic inulin-type fructans are widely consumed in the diet and may have contrasting effects in Crohn’s disease by stimulating gut microbiota and/or by generating functional gastrointestinal symptoms. The aim of this study was to measure fructan and oligofructose intakes in patients with active and inactive Crohn’s disease compared with healthy controls. Methods: Patients with active Crohn’s disease (n=98), inactive Crohn’s (n=99) and healthy controls (n=106) were recruited to a case-control study. Dietary intake of inulin-type fructans was measured using a specific food frequency questionnaire and was compared between the three groups and between patients with different disease phenotypes (Montreal classification). Associations between intakes and disease activity (Harvey Bradshaw Index, HBI) were also undertaken. Results: Patients with active Crohn’s disease had lower fructan intakes (median 2.9 g/d, IQR 1.8) than those with inactive Crohn’s (3.6 g/d, 2.1, P=0.036) or controls (3.9 g/d, 2.1, P=0.003) and lower oligofructose intakes (2.8 g/d, 1.8) than inactive Crohn’s (3.5 g/d, 2.2, P=0.048) or controls (3.8 g/d, 2.1, P=0.003). There were no differences in intakes related to disease site or behaviour. There were negative correlations between HBI wellbeing score and fructan intake (ρ=-0.154, P=0.03) and oligofructose intake (ρ=-0.156, P=0.028) and for the HBI abdominal pain score and fructan (ρ=-0.164, P=0.021) and oligofructose intake (ρ=-0.157, P=0.027). Conclusions: Patients with active Crohn’s disease consume lower quantities of fructans and oligofructose than their inactive counterparts and healthy controls. The impact of lower intakes of prebiotic fructans on gut microbiota are unknown and warrant further research

Siblings of patients with Crohn's disease exhibit a biologically relevant dysbiosis in mucosal microbial metacommunities

© 2016, BMJ Publishing Group. All rights reserved. Objective: To determine the existence of mucosal dysbiosis in siblings of patients with Crohn's disease (CD) using 454 pyrosequencing and to comprehensively characterise and determine the influence of genotypical and phenotypical factors, on that dysbiosis. Siblings of patients with CD have elevated risk of developing CD and display aspects of disease phenotype, including faecal dysbiosis. Whether the mucosal microbiota is disrupted in these at-risk individuals is unknown. Design: Rectal biopsy DNA was extracted from 21 patients with quiescent CD, 17 of their healthy siblings and 19 unrelated healthy controls. Mucosal microbiota was analysed by 16S rRNA gene pyrosequencing and were classified into core and rare species. Genotypical risk was determined using Illumina Immuno BeadChip, faecal calprotectin by ELISA and blood T-cell phenotype by flow cytometry. Results: Core microbiota of both patients with CD and healthy siblings was significantly less diverse than controls. Metacommunity profiling (Bray-Curtis (SBC) index) showed the sibling core microbial composition to be more similar to CD (SBC=0.70) than to healthy controls, whereas the sibling rare microbiota was more similar to healthy controls (SBC=0.42). Faecalibacterium prausnitzii contributed most to core metacommunity dissimilarity both between siblings and controls, and between patients and controls. Phenotype/genotype markers of CD risk significantly influenced microbiota variation between and within groups, of which genotype had the largest effect. Conclusions: Individuals with elevated CD-risk display mucosal dysbiosis characterised by reduced diversity of core microbiota and lower abundance of F. prausnitzii. This dysbiosis in healthy people at risk of CD implicates microbiological processes in CD pathogenesis

Ustekinumab treatment in ulcerative colitis : Real-world data from the Swedish inflammatory bowel disease quality register

Background Real-world data on clinical outcomes of ustekinumab in ulcerative colitis are lacking. Objective To assess short- and long-term clinical outcomes of ustekinumab in ulcerative colitis. Methods Adult ulcerative colitis patients without previous colectomy starting ustekinumab treatment up until 11 December 2020 were identified through the Swedish Inflammatory Bowel Disease Register (SWIBREG). Prospectively recorded data were extracted from the SWIBREG. The primary outcome was persistence to ustekinumab 16 weeks after treatment initiation. Secondary outcomes included drug persistence beyond week 16, clinical remission (defined as a patient-reported Mayo rectal bleeding subscore = 0 and stool frequency subscore &amp;lt;= 1), biochemical remission (defined as faecal-calprotectin &amp;lt;250 mu g/g) and changes in health-related quality of life (HRQoL), as measured by the Short Health Scale (SHS). Logistic regression was used to identify potential predictors of ustekinumab persistence at 16 weeks. Results Of the 133 patients with ulcerative colitis, only three were naive to biologics and tofacitinib. The persistence rates of ustekinumab were 115/133 (86%) at 16 weeks and 89/133 (67%) at last follow-up, that is, after a median follow-up of 32 (interquartile range 19-56) weeks. The clinical remission rates were 17% at 16 weeks and 32% at the last follow-up. The corresponding rates for biochemical remission were 14% and 23%. The median faecal-calprotectin concentration decreased from 740 mu g/g at baseline to 98 mu g/g at the last follow-up (p &amp;lt; 0.01, n = 37). Improvement was seen in each dimension of the SHS between baseline and last follow-up (p &amp;lt; 0.01 for each dimension, n = 46). Male sex was associated with ustekinumab persistence at 16 weeks (adjusted odds ratio = 4.00, 95% confidence interval: 1.35-11.83). Conclusion In this nationwide real-world cohort of ulcerative colitis patients with prior drug failures, including other biologics and tofacitinib, ustekinumab was associated with high drug persistence rates and improvements in clinical, biochemical and HRQoL measures.Funding Agencies|Janssen Pharmaceuticals [CNTO1275UCO0001]</p

Identification and validation of a blood- based diagnostic lipidomic signature of pediatric inflammatory bowel disease

Improved biomarkers are needed for pediatric inflammatory bowel disease. Here we identify a diagnostic lipidomic signature for pediatric inflammatory bowel disease by analyzing blood samples from a discovery cohort of incident treatment-naïve pediatric patients and validating findings in an independent inception cohort. The lipidomic signature comprising of only lactosyl ceramide (d18:1/16:0) and phosphatidylcholine (18:0p/22:6) improves the diagnostic prediction compared with high-sensitivity C-reactive protein. Adding high-sensitivity C-reactive protein to the signature does not improve its performance. In patients providing a stool sample, the diagnostic performance of the lipidomic signature and fecal calprotectin, a marker of gastrointestinal inflammation, does not substantially differ. Upon investigation in a third pediatric cohort, the findings of increased lactosyl ceramide (d18:1/16:0) and decreased phosphatidylcholine (18:0p/22:6) absolute concentrations are confirmed. Translation of the lipidomic signature into a scalable diagnostic blood test for pediatric inflammatory bowel disease has the potential to support clinical decision making