{"doi":"10.1101/2020.07.02.185082","title":"Primary human colonic mucosal barrier crosstalk with super oxygen-sensitive <i>Faecalibacterium prausnitzii</i> in continuous culture","abstract":"Abstract The gut microbiome plays an important role in human health and disease. Gnotobiotic animal and in vitro cell-based models provide some informative insights into mechanistic crosstalk. However, there is no existing system for a chronic co-culture of a human colonic mucosal barrier with super oxygen-sensitive commensal microbes, hindering the study of human-microbe interactions in a controlled manner. Here, we investigated the effects of an abundant super oxygen-sensitive commensal anaerobe, Faecalibacterium prausnitzii , on a primary human mucosal barrier using a Gut-MIcrobiome (GuMI) physiome platform that we designed and fabricated. Chronic continuous co-culture of F. prausnitzii for two days with colon epithelia, enabled by continuous flow of completely anoxic apical media and aerobic basal media, resulted in a strictly anaerobic apical environment fostering growth of and butyrate production by F. prausnitzii , while maintaining a stable colon epithelial barrier. We identified elevated differentiation and hypoxia-responsive genes and pathways in the platform compared with conventional aerobic static culture of the colon epithelia, attributable to a combination of anaerobic environment and continuous medium replenishment. Furthermore, we demonstrated anti-inflammatory effects of F. prausnitzii through HDAC and the TLR-NFKB axis. Finally, we identified that butyrate largely contributes to the anti-inflammatory effects by downregulating TLR3 and TLR4. Our results are consistent with some clinical observations regarding F. prausnitzii , thus motivating further studies employing this platform with more complex engineered colon tissues for understanding the interaction between the human colonic mucosal barrier and microbiota, pathogens, or engineered bacteria.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":130286,"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":0.9619,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":244105,"name":"Yu-Ja Huang","orcid":null,"position":1,"is_corresponding":false},{"id":582996,"name":"Jun–Young Yoon","orcid":null,"position":2,"is_corresponding":false},{"id":267209,"name":"John Kemmitt","orcid":"0000-0003-3523-3384","position":3,"is_corresponding":false},{"id":244107,"name":"Charles Wright","orcid":null,"position":4,"is_corresponding":false},{"id":244106,"name":"Kirsten Schneider","orcid":null,"position":5,"is_corresponding":false},{"id":267210,"name":"Pierre Sphabmixay","orcid":"0000-0003-0119-9173","position":6,"is_corresponding":false},{"id":253825,"name":"Victor Hernandez‐Gordillo","orcid":"0000-0003-4403-2541","position":7,"is_corresponding":false},{"id":267211,"name":"Steven J. Holcomb","orcid":"0000-0003-1100-4982","position":8,"is_corresponding":false},{"id":267212,"name":"Brij M. Bhushan","orcid":"0000-0003-3351-0990","position":9,"is_corresponding":false},{"id":269274,"name":"Gar Rohatgi","orcid":null,"position":10,"is_corresponding":false},{"id":267213,"name":"Kyle Benton","orcid":"0000-0002-2964-2627","position":11,"is_corresponding":false},{"id":267214,"name":"David Carpenter","orcid":"0000-0002-9261-7168","position":12,"is_corresponding":false},{"id":267215,"name":"Jemila C. Kester","orcid":"0000-0001-8639-284X","position":13,"is_corresponding":false},{"id":43383,"name":"George Eng","orcid":"0000-0003-4960-4705","position":14,"is_corresponding":false},{"id":253830,"name":"David T. Breault","orcid":"0000-0002-0402-4857","position":15,"is_corresponding":false},{"id":39713,"name":"Ömer Yılmaz","orcid":"0000-0002-0962-2725","position":16,"is_corresponding":false},{"id":269275,"name":"Mao Taketani","orcid":null,"position":17,"is_corresponding":false},{"id":267216,"name":"Christopher A. Voigt","orcid":"0000-0003-0844-4776","position":18,"is_corresponding":false},{"id":253831,"name":"Rebecca L. Carrier","orcid":"0000-0003-3002-7098","position":19,"is_corresponding":false},{"id":242599,"name":"David L. Trumper","orcid":"0000-0001-5358-5450","position":20,"is_corresponding":false},{"id":228222,"name":"Linda G. 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