Gut Microbiome and Metabonomic Profile Predict Early Remission to Anti-Integrin Therapy in Patients with Moderate to Severe Ulcerative Colitis

Liu, Jie; Fang, Huaying; Hong, Na; Lv, Chaolan; Zhu, Qi; Feng, Yinping; Wang, Bo; Tian, Jiashuang; Yu, Yue

doi:10.1128/spectrum.01457-23

Cited by 9 publications

(5 citation statements)

References 58 publications

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“…Verrucomicobiota has been reported to be one of the phyla present in the human gut, which has only one cultivated intestinal representative, Akkermansia muciniphila ( Derrien et al, 2017 ). Studies have shown that the abundance of Verrucomicrobiota was significantly lower in UC patients with active phase, while significantly higher in the remission phases than that of the healthy control group at the phylum level ( Zhu et al, 2022 ; Liu J. et al, 2023 ). Therefore, Verrucomicrobiota may offer potential prospects for future treatment of human UC.…”

Section: Discussionmentioning

confidence: 96%

Alterations in metabolome and microbiome: new clues on cathelicidin-related antimicrobial peptide alleviates acute ulcerative colitis

Jiang,

Liu,

Wang

et al. 2024

Front. Microbiol.

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Ulcerative colitis (UC) is a chronic and recurrent inflammatory disease of the gastrointestinal tract. This study aimed to determine the effect of cathelicidin-related antimicrobial peptide (Cramp) on dextran sulfate sodium (DSS)-induced acute experimental colitis in mice and to investigate the underlying mechanisms. Acute UC was induced in C57BL/6 mice with 3% DSS for 7 days, 4 mg/kg b.w. synthetic Cramp peptide was administrated once daily starting on day 4 of the experimental period. Mice were evaluated for body weight, colon length, colon histopathology, and inflammatory cytokines in colon tissue. Using 16 s rRNA sequencing, the composition structure of gut microbiota was characterized. Metabolomic profiling of the serum was performed. The results showed that DSS treatment significantly induced intestinal damage as reflected by disease activity index, histopathological features, and colon length, while Cramp treatment significantly prevented these trends. Meanwhile, Cramp treatment decreased the levels of inflammatory cytokines in both serum and colonic tissue on DSS-induced colitis. It was also observed that DSS damaged the integrity of the intestinal epithelial barrier, whereas Cramp also played a protective role by attenuating these deteriorated effects. Furthermore, Cramp treatment reversed the oxidative stress by increasing the antioxidant enzymes of GSH-PX and decreasing the oxidant content of MDA. Notably, compared to the DSS group, Cramp treatment significantly elevated the abundance of Verrucomicrobiota at the phylum level. Furthermore, at the genus level, Parasutterella and Mucispirllum abundance was increased significantly in response to Cramp treatment, although Roseburia and Enterorhabdus reduced remarkably. Metabolic pathway analysis of serum metabolomics showed that Cramp intervention can regulate various metabolic pathways such as α-linolenic acid, taurine and hypotaurine, sphingolipid, and arachidonic acid metabolism. The study concluded that Cramp significantly ameliorated DSS-induced colonic injury, colonic inflammation, and intestinal barrier dysfunction in mice. The underlying mechanism is closely related to the metabolic alterations derived from gut microbiota.

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Section: Discussionmentioning

confidence: 96%

Alterations in metabolome and microbiome: new clues on cathelicidin-related antimicrobial peptide alleviates acute ulcerative colitis

Jiang,

Liu,

Wang

et al. 2024

Front. Microbiol.

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“…Open access of stool showed significantly higher levels of SCFAs including butyrate in those achieving week 14 remission (defined as total Mayo score ≤2, all subscores ≤1) vs non-remitters. 19 Combining metabolite data (SCFA levels for butyrate and isobutyric acid) with microbial profile data predicted anti-integrin response with an AUC of 0.961. While these previous studies are important first steps to using gut microbial signatures in stratified treatment algorithms, they were mostly underpowered, examined single treatments, used different sequencing technologies and produced heterogeneous non-overlapping results.…”

Section: Strengths and Limitations Of This Studymentioning

confidence: 99%

Defining predictors of responsiveness to advanced therapies in Crohn’s disease and ulcerative colitis: protocol for the IBD-RESPONSE and nested CD-metaRESPONSE prospective, multicentre, observational cohort study in precision medicine

Wyatt,

Watson,

Anderson

et al. 2024

BMJ Open

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IntroductionCharacterised by chronic inflammation of the gastrointestinal tract, inflammatory bowel disease (IBD) symptoms including diarrhoea, abdominal pain and fatigue can significantly impact patient’s quality of life. Therapeutic developments in the last 20 years have revolutionised treatment. However, clinical trials and real-world data show primary non-response rates up to 40%. A significant challenge is an inability to predict which treatment will benefit individual patients.Current understanding of IBD pathogenesis implicates complex interactions between host genetics and the gut microbiome. Most cohorts studying the gut microbiota to date have been underpowered, examined single treatments and produced heterogeneous results. Lack of cross-treatment comparisons and well-powered independent replication cohorts hampers the ability to infer real-world utility of predictive signatures.IBD-RESPONSE will use multi-omic data to create a predictive tool for treatment response. Future patient benefit may include development of biomarker-based treatment stratification or manipulation of intestinal microbial targets. IBD-RESPONSE and downstream studies have the potential to improve quality of life, reduce patient risk and reduce expenditure on ineffective treatments.Methods and analysisThis prospective, multicentre, observational study will identify and validate a predictive model for response to advanced IBD therapies, incorporating gut microbiome, metabolome, single-cell transcriptome, human genome, dietary and clinical data. 1325 participants commencing advanced therapies will be recruited from ~40 UK sites. Data will be collected at baseline, week 14 and week 54. The primary outcome is week 14 clinical response. Secondary outcomes include clinical remission, loss of response in week 14 responders, corticosteroid-free response/remission, time to treatment escalation and change in patient-reported outcome measures.Ethics and disseminationEthical approval was obtained from the Wales Research Ethics Committee 5 (ref: 21/WA/0228). Recruitment is ongoing. Following study completion, results will be submitted for publication in peer-reviewed journals and presented at scientific meetings. Publications will be summarised at www.ibd-response.co.uk.Trial registration numberISRCTN96296121.

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“…Regardless of relapse status, IBD patients have lower isobutyrate levels than healthy individuals ( 106 ). Furthermore, isobutyrate and Verrucomicrobiota could serve as markers for diagnosing UC remission ( 108 ). Additionally, hexanoate might serve as a predictive indicator for CD patient relapse risk ( 25 ).…”

Section: Short-chain Fatty Acidsmentioning

confidence: 99%

“…Levels of butyrate and substrates are correlated with the remission outcomes of Infliximab treatment ( 214 ). Similarly, butyric acid and isobutyric acid can serve as biomarkers for patient responses to Vedolizumab ( 108 ). Furthermore, glucocorticoids, such as prednisolone, can directly reduce luminal lipid mediators like PGE2 and LTB4, improving IBD symptoms ( 215 , 216 ).…”

Section: Therapeutic Approaches Based On Fatty Acidsmentioning

confidence: 99%

Fatty acids and lipid mediators in inflammatory bowel disease: from mechanism to treatment

Yan,

Ye,

et al. 2023

Front. Immunol.

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Inflammatory Bowel Disease (IBD) is a chronic, relapsing inflammatory disorder of the gastrointestinal tract. Though the pathogenesis of IBD remains unclear, diet is increasingly recognized as a pivotal factor influencing its onset and progression. Fatty acids, essential components of dietary lipids, play diverse roles in IBD, ranging from anti-inflammatory and immune-regulatory functions to gut-microbiota modulation and barrier maintenance. Short-chain fatty acids (SCFAs), products of indigestible dietary fiber fermentation by gut microbiota, have strong anti-inflammatory properties and are seen as key protective factors against IBD. Among long-chain fatty acids, saturated fatty acids, trans fatty acids, and ω-6 polyunsaturated fatty acids exhibit pro-inflammatory effects, while oleic acid and ω-3 polyunsaturated fatty acids display anti-inflammatory actions. Lipid mediators derived from polyunsaturated fatty acids serve as bioactive molecules, influencing immune cell functions and offering both pro-inflammatory and anti-inflammatory benefits. Recent research has also highlighted the potential of medium- and very long-chain fatty acids in modulating inflammation, mucosal barriers, and gut microbiota in IBD. Given these insights, dietary intervention and supplementation with short-chain fatty acids are emerging as potential therapeutic strategies for IBD. This review elucidates the impact of various fatty acids and lipid mediators on IBD and delves into potential therapeutic avenues stemming from these compounds.

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Gut Microbiome and Metabonomic Profile Predict Early Remission to Anti-Integrin Therapy in Patients with Moderate to Severe Ulcerative Colitis

Cited by 9 publications

References 58 publications

Alterations in metabolome and microbiome: new clues on cathelicidin-related antimicrobial peptide alleviates acute ulcerative colitis

Alterations in metabolome and microbiome: new clues on cathelicidin-related antimicrobial peptide alleviates acute ulcerative colitis

Defining predictors of responsiveness to advanced therapies in Crohn’s disease and ulcerative colitis: protocol for the IBD-RESPONSE and nested CD-metaRESPONSE prospective, multicentre, observational cohort study in precision medicine

Fatty acids and lipid mediators in inflammatory bowel disease: from mechanism to treatment

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