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J Pharmacol Exp Ther 304:425432

Three key challenges persist: lack of core markers for highly efficient immune regulatory donors (specific bacterial genus combinations, metabolite profiles) leading to unstable transplantation effects

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Consequently, single-modality biomarkers frequently fail to generalize because they are sensitive to context (cycle phase, progesterone exposure timing, stimulation protocols, and tissue/cell-type composition), so an apparent signal in one layer may reflect unmeasured confounding rather than functional competence [447]