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Studies in metabolic disease consistently report elevated systemic LPS levels associated with dysbiosis and metabolic endotoxemia (Dong et al., 2022), and these increases correlate with -cell transcriptional stress signatures observed in scRNA-seq analyses, including the expansion of ATF4 + and XBP1 + subclusters and the downregulation of maturity-related transcription factors such as PDX1 and MAFA under inflammatory conditions (Sokolowski et al., 2024)