Correlation Between the Gut Microbiome and Immunotherapy Response in Inflammatory Bowel Disease: A Systematic Review of the Literature

Karpinska-Leydier, Katarzyna; Amirthalingam, Jashvini; Alshowaikh, Khadija; Jayarathna, Anuruddhika I Iroshani; Salibindla, Divya Bala Anthony Manisha R; Paidi, Gokul; Ergin, Huseyin Ekin

doi:10.7759/cureus.16808

Cited by 2 publications

(2 citation statements)

References 37 publications

(74 reference statements)

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“…Weak links have been found between CSTB and UC neoplastic progression 44 , and between PDCD6 and in iximab responses and brosis in CD 45,46 . Upregulation of PDCD6 interacting protein (PDCD6IP) has also been linked with UC 47 . PDGFRB has several approved drugs with indications including colorectal cancer and gastrointestinal stromal tumor which are major sequelae of IBD, and it forms heterodimers with PDGFRA which has been linked with colitis susceptibility 48 and postnatal intestinal epithelial stemness 49 .…”

Section: Discussionmentioning

confidence: 99%

Multiomics-based causal inference identifies novel therapeutic targets for inflammatory bowel disease in East Asians

Kim,

Lee,

Kim

et al. 2023

Preprint

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Multiomics-based efforts to identify therapeutic targets for IBD have been limited to European populations. Prior reports on heterogeneity between East Asians and Europeans in clinical manifestations of IBD and genetic architectures of IBD-related variants warrant a separate investigation in East Asians. Using the East Asian genome and proteome data, we applied two multiomics-based causal inference methods, proteome-wide Mendelian randomization and causal proteome-wide association study. For IBD, Crohn’s disease (CD), and ulcerative colitis (UC), we found 30 potential drug targets with proteomic evidence. IL18R1, IL1RL1, KIR3DL1, and MEP1B had consistent associations with across IBD, CD, and UC. Fifteen targets were CD-specific, while eight were UC-specific. Among the candidate targets, thirteen and eight had supportive MR evidence in the plasma transcriptome data and the multi-tissue transcriptome data of European ancestry, respectively. IL18R1, IL6R, IL16, TNFRSF14 or their direct interactors were currently targeted by drugs being developed to treat IBD. IL1RL1 and PDGFRB had existing drugs that may be repurposed for IBD. Crucially, we identified six previously unreported target genes, opening new avenues for therapeutic interventions in IBD that warrant immediate validation in upcoming experiments and clinical trials.

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Section: Discussionmentioning

confidence: 99%

Multiomics-based causal inference identifies novel therapeutic targets for inflammatory bowel disease in East Asians

Kim,

Lee,

Kim

et al. 2023

Preprint

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“…These alterations trigger local and systemic host inflammatory responses that progressively damage the intestines over time [5-6]. A hypothesis of how alterations in gut microbiota drive chronic inflammation in Crohn’s Disease and Ulcerative Colitis is through the gut metabolome which may act as an interface between the host and microbiome [7]. However, these mechanisms of metabolome-mediated host-microbiome interactions are poorly understood.…”

Section: Introductionmentioning

confidence: 99%

Latent Interacting Variable-Effects Modeling of Gut Microbiome Multi-Omics in Inflammatory Bowel Disease

Munoz

Brubaker

2022

Preprint

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Latent Interacting Variable Effects (LIVE) modeling is a framework to integrate different types of microbiome multi-omics data by combining latent variables from single-omic models into a structured meta-model to determine discriminative, interacting multi-omics features driving disease status. We implemented and tested LIVE modeling in publicly available metagenomics and metabolomics datasets from Crohns Disease and Ulcerative Colitis patients. Here, LIVE modeling reduced the number of feature correlations from the original data set for CD and UC to tractable numbers and facilitated prioritization of biological associations between microbes, metabolites, enzymes and IBD status through the application of stringent thresholds on generated inferential statistics. We determined LIVE modeling confirmed previously reported IBD biomarkers and uncovered potentially novel disease mechanisms in IBD. LIVE modeling makes a distinct and complementary contribution to the current methods to integrate microbiome data to predict IBD status because of its flexibility to adapt to different types of microbiome multi-omics data, scalability for large and small cohort studies via reliance on latent variables and dimensionality reduction, and the intuitive interpretability of the linear meta-model integrating -omic data types. The results of LIVE modeling and the biological relationships can be represented in networks that connect local correlation structure of single omic data types with global community and omic structure in the latent variable VIP scores. This model arises as novel tool that allows researchers to be more selective about omic feature interaction without disrupting the structural correlation framework provided by sPLS-DA interaction effects modeling. It will lead to form testable hypothesis by identifying potential and unique interactions between metabolome and microbiome that must be considered for future studies.

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Correlation Between the Gut Microbiome and Immunotherapy Response in Inflammatory Bowel Disease: A Systematic Review of the Literature

Cited by 2 publications

References 37 publications

Multiomics-based causal inference identifies novel therapeutic targets for inflammatory bowel disease in East Asians

Multiomics-based causal inference identifies novel therapeutic targets for inflammatory bowel disease in East Asians

Latent Interacting Variable-Effects Modeling of Gut Microbiome Multi-Omics in Inflammatory Bowel Disease

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