{"doi":"10.1016/j.soard.2021.07.019","title":"Toll-like receptor 4 and myeloid differentiation factor 88 are required for gastric bypass-induced metabolic effects","abstract":"BACKGROUND: Toll-like receptor 4 (TLR4) has been suggested as one of the forefront cross-communicators between the intestinal bacteria and the host to regulate inflammatory signals and energy homeostasis. High-fat diet-induced inflammation is mediated by changes in gut microbiota and requires a functional TLR-4, the deficiency of which renders mice resistant to diet-induced obesity and its associated metabolic dysfunction. Furthermore, gut microbiota was suggested to play a key role in the beneficial effects of Roux-en-Y gastric bypass (RYGB), a commonly performed bariatric procedure. OBJECTIVES: To explore whether TLR4, myeloid differentiation factor 8 (MyD88; 1 of its key downstream signaling regulators) and gut microbiota play an integrative role in RYGB-induced metabolic outcomes. SETTING: Animal- based study. METHOD: We performed RYGB in TLR4 and MyD88 knock-out (KO) mice and used fecal microbiota transplant (FMT) from RYGB-operated animals to these genetic mouse models to address our questions. RESULTS: We demonstrate that RYGB reduces TLR4 expression explicitly in the small and large intestine of C57Blc/6J mice. We also show that TLR4 KO mice have an attenuated glucoregulatory response to RYGB. In addition, we reveal that MyD88 KO mice fail to respond to all RYGB-induced metabolic effects. Finally, fecal microbiota transplant from RYGB-operated mice into TLR4 KO and MyD88 KO naïve recipients fails to induce a metabolic phenotype similar to that of the donors, as it does in wild-type recipients. CONCLUSION: TLR4 and MyD88 are required for RYGB-induced metabolic response that is likely mediated by gut microbiome.","journal":"Surgery for Obesity and Related Diseases","year":2021,"id":200332,"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":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9615,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":462573,"name":"Yuanchao Ye","orcid":null,"position":1,"is_corresponding":false},{"id":697404,"name":"Yi Chu","orcid":null,"position":2,"is_corresponding":false},{"id":777987,"name":"Hussein Herz","orcid":"0000-0003-0549-6298","position":3,"is_corresponding":false},{"id":778671,"name":"Benjamin Linden","orcid":null,"position":4,"is_corresponding":false},{"id":456165,"name":"Shailesh K. Shahi","orcid":"0000-0002-8506-7655","position":5,"is_corresponding":false},{"id":461489,"name":"Kasra Zarei","orcid":"0000-0002-1531-0111","position":6,"is_corresponding":false},{"id":340390,"name":"Ashutosh K. Mangalam","orcid":"0000-0002-9926-2531","position":7,"is_corresponding":false},{"id":245816,"name":"Steven J. McElroy","orcid":"0000-0002-4321-723X","position":8,"is_corresponding":false},{"id":461496,"name":"Mohamad Mokadem","orcid":"0000-0003-1402-580X","position":9,"is_corresponding":false},{"id":461485,"name":"Marwa Abu El Haija","orcid":"0000-0003-1770-1367","position":0,"is_corresponding":true}],"reference_count":46,"raw_metadata":null,"created_at":"2026-07-18T23:50:48.624274Z","pmid":"34462225","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":[]}