Multiomic features associated with mucosal healing and inflammation in paediatric Crohn’s disease

Taylor, Henry M.; Serrano-Contreras, José Iván; McDonald, Julie A. K.; Epstein, Jenny; Fell, J.; Seoane, R.; Li, Jia V.; Marchesi, Julian R.; Hart, Ailsa

doi:10.1111/apt.16086

Cited by 22 publications

(17 citation statements)

References 63 publications

(105 reference statements)

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“…Finally, most of the studies presented herein tackle the question of how the gut microbiota relate to IBD treatment by analysing “who is there,” not “what are they doing?” The absence of information on microbiome functional output, for example in the form of metabonomics or proteomics, limits the conclusions that can be drawn at this stage 73 . A recent publication has investigated both the microbiota and metabolic profile of CD patients, concluding that patients with a FC of <100 μg/g exhibited a higher relative abundance of the Dialister genus with higher relative concentrations of valerate 74 . Future work should also adopt a combined “multi‐omic” approach to analyses to fully investigate bacterial populations and their function.…”

Section: Discussion/conclusionmentioning

confidence: 99%

Systematic review: the association between the gut microbiota and medical therapies in inflammatory bowel disease

Radhakrishnan

Alexander

Mullish

et al. 2021

Aliment Pharmacol Ther

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Summary Background The gut microbiota has been implicated in the pathogenesis of inflammatory bowel disease (IBD), with Faecalibacterium prausnitizii associated with protection, and certain genera (including Shigella and Escherichia) associated with adverse features. The variability of patient response to medical therapies in IBD is incompletely understood. Given the recognised contribution of the microbiota to treatment efficacy in other conditions, there may be interplay between the gut microbiota, IBD medical therapy and IBD phenotype. Aims To evaluate the bidirectional relationship between IBD medical therapies and the gut microbiota. Methods We conducted a systematic search of MEDLINE and EMBASE. All original studies analysing interactions between the gut microbiota and established IBD medical therapies were included. Results We screened 1296 records; 19 studies were eligible. There was heterogeneity in terms of sample analysis, treatment protocols, and outcome reporting. Increased baseline α‐diversity was observed in responders versus non‐responders treated with exclusive enteral nutrition (EEN), infliximab, ustekinumab or vedolizumab. Higher baseline Faecalibacterium predicted response to infliximab and ustekinumab. A post‐treatment increase in Faecalibacterium prausnitzii was noted in responders to aminosalicylates, anti‐TNF medications and ustekinumab; conversely, this species decreased in responders to EEN. Escherichia was a consistent marker of unfavourable drug response, and its presence in the gut mucosa correlated with inflammation in aminosalicylate‐treated patients. Conclusions Both gut microbiota diversity and specific taxonomic features (including high abundance of Faecalibacterium) are associated with the efficacy of a range of IBD therapies. These findings hold promise for a potential role for the gut microbiota in explaining the heterogeneity of patient response to IBD treatments.

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Section: Discussion/conclusionmentioning

confidence: 99%

Systematic review: the association between the gut microbiota and medical therapies in inflammatory bowel disease

Radhakrishnan

Alexander

Mullish

et al. 2021

Aliment Pharmacol Ther

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“…We found it enriched in mucosa and feces of IBD patients, in agreement with recent study comparing rectal biopsies of IBD patients to healthy controls. 23 In contrast, reduction of Dialister has been reported in feces of newly diagnosed 62 and a small cohort of established pediatric CD patients, 63 where lower abundance of Dialister was associated with increased calprotectin levels. We also detected an increase of Propionibacterium acnes , a known member of skin microbiota, in mucosa of UC patients.…”

Section: Discussionmentioning

confidence: 93%

Gut microbiota in mucosa and feces of newly diagnosed, treatment-naïve adult inflammatory bowel disease and irritable bowel syndrome patients

et al. 2022

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The knowledge on how gut microbes contribute to the inflammatory bowel disease (IBD) at the onset of disease is still scarce. We compared gut microbiota in newly diagnosed, treatment-naïve adult IBD (Crohn’s disease (CD) and ulcerative colitis (UC)) to irritable bowel syndrome (IBS) patients and healthy group. Mucosal and fecal microbiota of 49 patients (13 UC, 10 CD, and 26 IBS) before treatment initiation, and fecal microbiota of 12 healthy subjects was characterized by 16S rRNA gene sequencing. Mucosa was sampled at six positions, from terminal ileum to rectum. We demonstrate that mucosal microbiota is spatially homogeneous, cannot be differentiated based on the local inflammation status and yet provides bacterial footprints superior to fecal in discriminating disease phenotypes. IBD groups showed decreased bacterial diversity in mucosa at all taxonomic levels compared to IBS. In CD and UC, Dialister was significantly increased, and expansion of Haemophilus and Propionibacterium characterized UC. Compared to healthy individuals, fecal microbiota of IBD and IBS patients had increased abundance of Proteobacteria, Enterobacteriaceae , in particular. Shift toward reduction of Adlercreutzia and butyrate-producing taxa was found in feces of IBD patients. Microbiota alterations detected in newly diagnosed treatment-naïve adult patients indicate that the microbiota changes are set and detectable at the disease onset and likely have a discerning role in IBD pathophysiology. Our results justify further investigation of the taxa discriminating between disease groups, such as H. parainfluenzae, R. gnavus, Turicibacteriaceae, Dialister , and Adlercreutzia as potential biomarkers of the disease.

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“…Furthermore, the association between fecal metabolites and mucosal healing (using calprotectin levels as a surrogate) in pediatric CD was explored in a recent study. 27 As a principal discriminator, fecal pentanoate was detected at higher concentrations in the low calprotectin group, while fecal lysine was upregulated in the high calprotectin group. A similar result was also reported in another study.…”

Section: Metabolomics For Assessing Disease Activity In Ibdmentioning

confidence: 96%

Metabolomics facilitate the personalized management in inflammatory bowel disease

Chen

Zheng

et al. 2021

Therap Adv Gastroenterol

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Inflammatory bowel disease (IBD) is a gastrointestinal disorder characterized by chronic relapsing inflammation and mucosal lesions. Reliable biomarkers for monitoring disease activity, predicting therapeutic response, and disease relapse are needed in the personalized management of IBD. Given the alterations in metabolomic profiles observed in patients with IBD, metabolomics, a new and developing technique for the qualitative and quantitative study of small metabolite molecules, offers another possibility for identifying candidate markers and promising predictive models. With increasing research on metabolomics, it is gradually considered that metabolomics will play a significant role in the management of IBD. In this review, we summarize the role of metabolomics in the assessment of disease activity, including endoscopic activity and histological activity, prediction of therapeutic response, prediction of relapse, and other aspects concerning disease management in IBD. Furthermore, we describe the limitations of metabolomics and highlight some solutions.

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Multiomic features associated with mucosal healing and inflammation in paediatric Crohn’s disease

Abstract: This is an open access article under the terms of the Creat ive Commo ns Attri bution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 22 publications

References 63 publications

Systematic review: the association between the gut microbiota and medical therapies in inflammatory bowel disease

Systematic review: the association between the gut microbiota and medical therapies in inflammatory bowel disease

Gut microbiota in mucosa and feces of newly diagnosed, treatment-naïve adult inflammatory bowel disease and irritable bowel syndrome patients

Metabolomics facilitate the personalized management in inflammatory bowel disease

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