biorxiv2026-09-03immunologycancermetabolism
Stool valerate marks CAR-T dysbiosis; the fatty acid itself opens chromatin differently than butyrate
Low stool valerate at CAR-T eligibility tracks a fiber-fermenter-poor, SCFA-poor microbiome. PIM antibiotics leave CD4-skewed, AP-1-high products that predict worse survival. Ex vivo valerate, unlike butyrate or propionate, engages KLF/SP/EGR, opens KLF4, and induces AP-1 and MHC II, while propionate prefers low-mitochondrial-content states. The organelle note is that propionate commitment, not valerate's main act.
Finding. Patients heading to CD19 CAR T with a valerate-poor stool already have a fiber-fermenter-poor, SCFA-poor gut. Rehman, Tanner and colleagues tie that state to worse products after anaerobe-killing antibiotics: CD4-skewed, AP-1-high cells that predict short progression-free survival. Feed CAR T cells valerate and the chromatin looks unlike butyrate or propionate (KLF/SP/EGR, KLF4 open, AP-1 and MHC II). Propionate, not valerate, steers cells into low-mitochondrial-content states.
Score 66. Microbiome-CAR T, a mitochondrial aside on propionate. Medium confidence.
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Source preprint
Microbial valerate is associated with CAR T dysbiosis and its supplementation enhances CAR T function in B-cell lymphoma
10.64898/2026.09.01.748711
Rehman L, Song W, Rehman A, Singh K, Rawat SG, Darbaniyan F, Le CC, Aletti FM, Weng J, Liu J, Cheng X, Tang Y, Patchva S, Richard MD, Chu F, Cao J, Flowers CR, Shpall EJ, Tanner MR, Fahrmann J, Elinav E, Stein-Thoeringer CK, Jain MD, Jenq RR, Jain A, Neelapu SS, Zheng Y, Saini NY.
