Key result
Gut lymph demonstrates distinct proteomic and lipidomic enrichment, including selective CCL21 and IGFBP7 elevation versus plasma.
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Comprehensive multiomic profiling unveils selective biomolecular partitioning of proteins and lipids into lymphatic versus venous outflows in the gastrointestinal tract.
BACKGROUND: The venous and lymphatic outflows from organs may contain molecular signatures related to tissue function, but deep biomolecular analyses that compare outflow composition are lacking. Here, using blood and lymph samples from a piglet model system and mass spectrometry analysis, we compare protein and lipid cargo from 9 venous and 3 lymph depots centered on intestinal outflow. METHODS: We obtained venous blood and plasma from piglets using new methods for dissection and sample collection. We applied mass spectrometry–based proteomics and lipidomics, using both a low-volume method and an additional proteomics sample preparation method, the Seer Proteograph XT high coverage method for the proteomics. RESULTS: We detected 622 proteins and 1315 lipids across lymph and plasma. With the additional Seer proteomics method, we detected a further 7771 proteins across a subset of samples. We observed both expected and novel enrichments of proteins, including CCL21 and IGFBP (insulin-like growth factor-binding protein) 7 as proteins strongly enriched in lymph. When comparing lymph depots, we found that thoracic duct lymph is distinct from lymph draining the proximal and distal small intestine, especially in their lipidomic profiles, reflecting differences in dietary lipid uptake. By performing integrative multiomics of proteomics and lipidomics, we show that apos (apolipoproteins), such as the related apoA1 and apoA2 proteins, correlate with different lipid profiles and may associate with distinct functions across the plasma depots. CONCLUSIONS: These data identify molecules and biomarkers selectively enriched in adjacent lymph and venous drainage depots from the gastrointestinal tract. The analyses and figures present in this work are expanded upon in an interactive companion Web application at gutveinlymphomics.com, facilitating access to our integrated multiomics and advancing understanding of biomolecular trends across the intestinal tract.
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Anderson et al. (2026) studied Healthy female piglets (n=7). Lymphatic outflow from gastrointestinal tract vs. Venous blood outflow from adjacent gastrointestinal sites was evaluated on Proteomic and lipidomic differences between lymph and plasma depots. Mass spectrometry-based analysis identified 8351 proteins and 1315 lipids across distinct gut-associated depots, revealing selective enrichments of molecules such as CCL21 and IGFBP7 in lymph compared to venous plasma.
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