{"doi":"10.1101/2025.10.26.683539","title":"Host transcriptional responses to gut microbiome variation arising from urbanism","abstract":"ABSTRACT Gut microbiomes of urban communities are compositionally different from their rural counterparts, and are associated with immune dysregulation and gastrointestinal disease. However, it is unknown whether these compositional differences impact host physiology, and through what mechanisms. Here, we used human colonic epithelial cells to directly compare host transcriptional changes induced by gut microbiomes from urban versus rural communities. We co-cultured host cells with live, stool-derived gut microbiomes from Rwanda, Ghana, Nigeria, Malaysia, and the United States, and quantified transcriptional responses using RNA-seq. We found that urban microbiomes affected innate immune pathways, including TNF signaling and bacterial antigen recognition. We also found that high-diversity microbiomes elicited a stronger host transcriptional response, while low-diversity microbiomes triggered epithelial restructuring and glycolysis. Finally, specific taxa driving these effects, including Bifidobacterium adolescentis and Bacteroides dorei , correlated with lifestyle factors such as diet. These findings demonstrate that urbanization-associated microbiome changes directly influence host epithelial gene expression.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":579163,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9445,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1204528,"name":"Shreya Nirmalan","orcid":"0000-0002-1946-0168","position":1,"is_corresponding":false},{"id":236860,"name":"Adnan Alazizi","orcid":"0000-0002-7599-8114","position":2,"is_corresponding":false},{"id":567476,"name":"Henriette Mair-Meijers","orcid":"0000-0002-2422-3650","position":3,"is_corresponding":false},{"id":1454088,"name":"Adwoa Agyei","orcid":null,"position":4,"is_corresponding":false},{"id":867428,"name":"Mary Afihene","orcid":"0000-0003-2318-4976","position":5,"is_corresponding":false},{"id":761791,"name":"Shadrack Osei Asibey","orcid":"0000-0002-4258-6885","position":6,"is_corresponding":false},{"id":1432454,"name":"Yaw Asante Awuku","orcid":"0000-0001-8307-2242","position":7,"is_corresponding":false},{"id":1432456,"name":"Amoako Duah","orcid":"0000-0001-8104-7393","position":8,"is_corresponding":false},{"id":1432460,"name":"Amelie Plymoth","orcid":"0000-0001-8686-3760","position":9,"is_corresponding":false},{"id":1432452,"name":"Yvonne Ayerki Nartey","orcid":"0000-0003-2891-3082","position":10,"is_corresponding":false},{"id":13968,"name":"Lewis R. Roberts","orcid":"0000-0001-7885-8574","position":11,"is_corresponding":false},{"id":510640,"name":"Kenneth Valles","orcid":"0000-0003-0311-5949","position":12,"is_corresponding":false},{"id":1453589,"name":"Fatimah Alibrahim","orcid":"0000-0002-4361-9984","position":13,"is_corresponding":false},{"id":281205,"name":"Yvonne Ai Lian Lim","orcid":"0000-0003-4050-6332","position":14,"is_corresponding":false},{"id":1489810,"name":"Tan Maw Pin","orcid":null,"position":15,"is_corresponding":false},{"id":1453592,"name":"Charles Onyekwere","orcid":"0000-0002-2777-1628","position":16,"is_corresponding":false},{"id":1454100,"name":"John Rusine","orcid":null,"position":17,"is_corresponding":false},{"id":1454097,"name":"Ivan E. Mwikarago","orcid":null,"position":18,"is_corresponding":false},{"id":29035,"name":"Eric J. Alm","orcid":"0000-0001-8294-9364","position":19,"is_corresponding":false},{"id":564934,"name":"Mathilde Poyet","orcid":"0000-0001-6905-9017","position":20,"is_corresponding":false},{"id":1329625,"name":"Mathieu Groussin","orcid":"0000-0002-0942-7217","position":21,"is_corresponding":false},{"id":236859,"name":"Francesca Luca","orcid":"0000-0001-8252-9052","position":22,"is_corresponding":false},{"id":20926,"name":"Ran Blekhman","orcid":"0000-0003-3218-613X","position":23,"is_corresponding":false},{"id":824963,"name":"Sabrina J. Arif","orcid":"0000-0002-4888-3215","position":0,"is_corresponding":true}],"reference_count":99,"raw_metadata":null,"created_at":"2026-07-19T02:58:30.282164Z","pmid":"41278623","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}