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Ultra-performance liquid chromatographytandem mass spectrometry (UPLC-MS/MS) enables precise quantification of structurally diverse BA species (175, 176), facilitating detailed characterization of the bile acid-ome. The emerging field of reverse metabolomics further accelerates the discovery of novel bioactive BA derivatives, including previously unannotated microbial metabolites, directly detected in human-derived biospecimens ( Beyond bulk analyses, single-cell technologies such as single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics/metabolomics are now providing unprecedented resolution of cellular heterogeneity and spatio-temporal BA signaling within the TIME and associated mucosal tissues (177)

Furthermore, low levels of BDNF inhibit the effective translocation of Nrf2 to the nucleus, impairing Nrf2 pathway functionality and limiting the activation of antioxidant mechanisms, ultimately resulting in persistent oxidative stress (Bouvier et al., 2017)