Ribo-TRAPseq identifies spacially distinct roles for the anterior and posterior intestine for metabolic regulation in C. elegans

Animals must couplefood-relatedcuesin the intestinetotheirphysiology, yetit is unclearwhether discrete intestinal segments specialize in this sensing.Here, we generatecelltype-resolved translatomes of the anterior intestinal ring (INT1) and the remaining intestine (INT2-9)inCaenorhabditis elegansusing celltype-specific TRAP-seq under acute and chronicfasting/refeedingconditions. Across states, INT1 shows adistinct identity enriched for immuneand stress-response programs, including C-type lectinsand ShKT-domain families. INT1-targeted perturbations alter bacterial avoidance and survival, indicating specialized immunefunctions. Fasting/refeeding elicit divergent regulatory dynamics; modulating INT1 undulatinggeneschangesthesecretiondynamicsof an INT1-derived enteroendocrine peptide, INS-7.Mechanosensation or bacterial supernatant fails to resetthesecretionof INS-7after fasting,whereasbacteria or pyruvate restore basal levels. Pyruvate requires mitochondrial import andmetabolism;anacute blockade of pyruvate processing prevents refeeding normalization.Thus,we identify INT1 as sentinel enteroendocrine sensors that couple pyruvate-dependentmitochondrial metabolism toenteroendocrine output, providing a resource for segment-specificintestinal biology. Overall design: Ribo-TRAPseq profiling of C. elegans intestinal cells (INT1 vs INT2-9) under fasting (acute/30min vs chronic/90min) and refeeding (acute/30min vs chronic/90min) conditions.