{"doi":"10.1016/j.jtct.2021.12.015","title":"Antibiotic Exposure, Not Alloreactivity, Is the Major Driver of Microbiome Changes in Hematopoietic Cell Transplantation","abstract":"Both autologous hematopoietic cell transplantation (auto-HCT) and allogeneic hematopoietic cell transplantation (allo-HCT) are associated with significant alterations in the intestinal microbiome. The relative contributions of antibiotic use and alloreactivity to microbiome dynamics have not yet been elucidated, however. There is a lack of data on the kinetics of microbiome changes beyond 30 days post-transplantation and how they might differ between different transplantation modalities. A direct comparison of the differential effects of auto-HCT and allo-HCT on the microbiome may shed light on these dynamics. This study was conducted to compare intestinal microbial diversity between auto-HCT recipients and allo-HCT recipients from pre-transplantation to 100 days post-transplantation, and to examine the effect of antibiotics, transplant type (auto versus allo), and conditioning regimens on the dynamics of microbiome recovery. We conducted a longitudinal analysis of changes in the intestinal microbiome in 35 patients undergoing HCT (17 auto-HCT, 18 allo-HCT) at 4 time points: pre-conditioning and 14, 28, and 100 days post-transplantation. Granular data on antibiotic exposure from day -30 pre-transplantation to day +100 post-transplantation were collected. Pre-transplantation, allo-HCT recipients had lower α-diversity in the intestinal microbiome compared with auto-HCT recipients, which correlated with greater pre-transplantation antibiotic use in allo-HCT recipients. The microbiome diversity declined at days +14 and +28 post-transplantation in both cohorts but generally returned to baseline by day +100. Conditioning regimen intensity did not significantly affect post-transplantation α-diversity. Through differential abundance analysis, we show that commensal bacterial taxa involved with maintenance of gut epithelial integrity and production of short-chain fatty acids were depleted after both auto-HCT and allo-HCT. In our dataset, antibiotic exposure was the major driver of post-transplantation microbiome changes rather than alloreactivity, conditioning intensity, or immunosuppression. Our findings also suggest that interventions to limit microbiome injury, such as limiting the use of broad-spectrum antibiotics, should target the pre-transplantation period and not only the peri-transplantation period.","journal":"Transplantation and Cellular Therapy","year":2021,"id":174996,"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":23,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9501,"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":715278,"name":"Heekuk Park","orcid":"0000-0001-5815-9717","position":1,"is_corresponding":false},{"id":716075,"name":"Cristian Taborda","orcid":null,"position":2,"is_corresponding":false},{"id":703437,"name":"Christian Gordillo","orcid":"0000-0003-4829-1954","position":3,"is_corresponding":false},{"id":407166,"name":"Markus Y. Mapara","orcid":"0000-0002-8547-8905","position":4,"is_corresponding":false},{"id":339777,"name":"Amer Assal","orcid":"0000-0003-4707-9265","position":5,"is_corresponding":false},{"id":246804,"name":"Anne‐Catrin Uhlemann","orcid":"0000-0002-9798-4768","position":6,"is_corresponding":false},{"id":471089,"name":"Ran Reshef","orcid":"0000-0003-2185-9546","position":7,"is_corresponding":false},{"id":715277,"name":"Rajat Bansal","orcid":"0000-0003-1461-3900","position":0,"is_corresponding":true}],"reference_count":62,"raw_metadata":null,"created_at":"2026-07-18T23:47:11.249697Z","pmid":"34958974","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":[]}