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pmid:36544093
Markers of immune dysregulation in response to the ageing gut: insights from aged murine gut microbiota transplants.
Panagiotis Giannos · Konstantinos Prokopidis · Masoud Isanejad · Helen L Wright
BMC gastroenterology · 2022 doi:10.1186/s12876-022-02613-2
Paper
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Experiment
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Analysis
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Complete file
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Genetic insights into the interaction between age-related alterations in the gut microbiota and immune function remain largely unexplored.\nMETHODS: We investigated publicly available transcriptomic gut profiles of young germ-free mouse hosts transplanted with old donor gut microbiota to identify immune-associated differentially expressed genes (DEGs). Literature screening of the Gene Expression Omnibus and PubMed identified one murine (Mus musculus) gene expression dataset (GSE130026) that included small intestine tissues from young (5-6 weeks old) germ-free mice hosts that were compared following 8 weeks after transplantation with either old (~ 24-month old; n = 5) or young (5-6 weeks old; n = 4) mouse donor gut microbiota.\nRESULTS: A total of 112 differentially expressed genes (DEGs) were identified and used to construct a gut network of encoded proteins, in which DEGs were functionally annotated as being involved in an immune process based on gene ontology. The association between the expression of immune-process DEGs and abundance of immune infiltrates from gene signatures in normal colorectal tissues was estimated from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) project. The analysis revealed a 25-gene signature of immune-associated DEGs and their expression profile was positively correlated with naïve T-cell, effector memory T-cell, central memory T-cell, resident memory T-cell, exhausted T-cell, resting Treg T-cell, effector Treg T-cell and Th1-like colorectal gene signatures. Conclusions These genes may have a potential role as candidate markers of immune dysregulation during gut microbiota ageing. Moreover, these DEGs may provide insights into the altered immune response to microbiota in the ageing gut, including reduced antigen presentation and alterations in cytokine and chemokine production.", "claims": [{"id": "claim-method", "statement": "Differentially expressed genes were retrieved using GEO2R according to the linear models for microarray analysis.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36544093", "locator": "sections[4] \"Identification of differentially expressed genes\" paragraph 2", "quote": "Differentially expressed genes were retrieved using GEO2R according to the linear models for microarray analysis."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets analysed during the current study are available in the NCBI Gene Expression Omnibus repository (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE130026).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36544093", "locator": "sections[25] \"Data availability\" paragraph 2", "quote": "The datasets analysed during the current study are available in the NCBI Gene Expression Omnibus repository (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE130026)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The analysis revealed a 25-gene signature of immune-associated DEGs and their expression profile was positively correlated with naïve T-cell, effector memory T-cell, central memory T-cell, resident memory T-cell, exhausted T-cell, resting Treg T-cell, effector Treg T-cell and Th1-like colorectal gene signatures.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:36544093", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "The analysis revealed a 25-gene signature of immune-associated DEGs and their expression profile was positively correlated with naïve T-cell, effector memory T-cell, central memory T-cell, resident memory T-cell, exhausted T-cell, resting Treg T-cell, effector Treg T-cell and Th1-like colorectal gene signatures."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The analysis revealed a 25-gene signature of immune-associated DEGs and their expression profile was positively correlated with naïve T-cell, effector memory T-cell, central memory T-cell, resident memory T-cell, exhausted T-cell, resting Treg T-cell, effector Treg T-cell and Th1-like colorectal gene signatures.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:36544093"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE130026"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE130026"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:36544093", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1186/s12876-022-02613-2", "sha256": "sha256:b9a87dab05bff969056d10bfa6f34ff53eacc6ddbb70af37c491e3f204d64565", "bytes": 54694, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1186/s12876-022-02613-2", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC9773626", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE130026", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE130026", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE130026", "version": null, "note": "The datasets analysed during the current study are available in the NCBI Gene Expression Omnibus repository (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE130026).", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets analysed during the current study are available in the NCBI Gene Expression Omnibus repository (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE130026).", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM3730319", "GSM3730320", "GSM3730321", "GSM3730322", "GSM3730323", "GSM3730324", "GSM3730325", "GSM3730326", "GSM3730327", "GSM3730328", "GSM3730329", "GSM3730330", "GSM3730331", "GSM3730332", "GSM3730333", "GSM3730334", "GSM3730335", "GSM3730336"], "sample_count": 18, "group_sizes": null, "group_sizes_basis": null, "platform": "17400", "taxon": "Mus musculus", "title": "Gut microbiota from old mice confers neurogenic and pro-longevity signatures in young germ-free mice", "resolution_checked_at": "2026-11-01T18:46:34Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE130026 not downloaded", "asset:data:geo:GSE130026 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": null, "specific": null, "label": "linear models for microarray analysis", "dsl_operations": [], "missing_operations": [], "expressible": null, "parameters": {}, "data_shapes": [], "evidence": {"score": 1.0, "band": "verbatim", "quote": "Differentially expressed genes were retrieved using GEO2R according to the linear models for microarray analysis."}}], "targets": [], "gaps": ["method.reader_named_unmapped"]}, "capability": {"state": "complete", "requirements": [{"capability_id": "capability:computational_analysis", "label": "Computational analysis platform", "assay_families": ["meta_analysis", "machine_learning", "survival_analysis", "statistical_regression", "pca", "molecular_docking", "network_analysis", "differential_expression", "gwas"], "availability_state": "owned", "tier_unlocked": "R1", "candidate": "Automated Assays Laravel application and simulated adapters"}], "gaps": []}, "readiness": {"state": "blocked", "tier": "R4", "blocking_axis": "method", "blocked_on": "method:not_determinable", "axes": {"method": {"tier": "R4", "expressible": false, "required_operations": [], "missing_operations": [], "basis": "The reader quoted the method the paper names (linear models for microarray analysis), but the corpus's method extractor could not map it onto a DSL operation, so the method is published but not expressible."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. 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