The TaxUMAP atlas: efficient display of large clinical microbiome data reveals ecological competition involved in protection against bacteremia

The microbiome is associated with health and disease, but causal effects are hard to quantify— especially in humans where controlled experiments are nearly impossible. Akin to natural experiments, closely monitored patients offer an alternative to characterize microbiome effects. We present TaxUMAP, a taxonomically-informed visualization method to effectively display diverse microbiome states. TaxUMAP charts a microbiome atlas from 1,870 cancer patients as they progress through therapy-induced perturbations, and quantifies the microbiome contribution to patients’ risk for life-threatening bacteremia. We find that the lowest diversity states (gut dominations) that follow antibiotic treatments are stable, and that diverse communities harbor more diverse antimicrobial resistance genes than dominations. We reveal that certain Klebsiella species are associated with reduced risk for bacteremia, an effect driven by bacterial competition that we validate experimentally in vitro and in vivo . TaxUMAP effectively maps longitudinal microbiome data that can facilitate research into causal microbiome effects on human health. HIGHLIGHTS ### Competing Interest Statement J.S. is cofounder of Postbiotics Plus Research LLC. J.U.P. reports research funding, intellectual property fees, and travel reimbursement from Seres Therapeutics, and consulting fees from DaVolterra, CSL Behring, and from MaaT Pharma, serves on an Advisory board of and holds equity in Postbiotics Plus Research LLC, has filed intellectual property applications related to the microbiome (reference numbers #62/843,849, #62/977,908, and #15/756,845). M.-A.P. received honoraria from AbbVie, Bellicum, Celgene, Bristol Myers Squibb, Incyte, Merck, Novartis, Nektar Therapeutics, Omeros, and Takeda, served on data safety monitoring boards for Cidara Therapeutics, Servier, and Medigene and scientific advisory boards for MolMed and NexImmune, has received research support for clinical trials from Incyte, Kite/Gilead, and Miltenyi Biotec, has served as a volunteer for and as a member of the Board of Directors of American Society for Transplantation and Cellular Therapy and Be The Match (National Marrow Donor Program), and on the Center for International Blood and Marrow Transplant Research Cellular Immunotherapy Data Resource Committee. A.S.B. is on the advisory board of Caribou Biosciences, and ArcBio, and has served as a paid consultant for BiomX and Guardant Health. M.R.M.v.d.B. has received research support and stock options from Seres Therapeutics and stock options from Notch Therapeutics and Pluto Therapeutics; has received royalties from Wolters Kluwer; has consulted, received honorarium from or participated in advisory boards for Seres Therapeutics, WindMIL Therapeutics, Rheos Medicines, Merck – Co, Inc., Magenta Therapeutics, Frazier Healthcare Partners, Nektar Therapeutics, Notch Therapeutics, Forty Seven Inc., Ceramedix, Lygenesis, Pluto Therapeutics, GlaskoSmithKline, Da Volterra, Novartis (Spouse), Synthekine (Spouse), and Beigene (Spouse), has IP Licensing with Seres Therapeutics and Juno Therapeutics, he holds a fiduciary role on the Foundation Board of DKMS (a nonprofit organization). E.G.P. has received speaker honoraria from Bristol Myers Squibb, Celgene, Seres Therapeutics, MedImmune, Novartis, and Ferring Pharmaceuticals and is an inventor on patent application #WPO2015179437A1 (entitled "Methods and compositions for reducing Clostridium difficile infection") and #WO2017091753A1 (entitled "Methods and compositions for reducing vancomycin-resistant enterococci infection or colonization") and holds patents that receive royalties from Seres Therapeutics. All other authors declare no competing interests.