Dynamic analysis of metabolomics reveals the potential associations between colonic peptides and serum appetite-related hormones

Gut signals, including hormones and metabolites are crucial zeitgebers that regulate the circadian rhythm of host metabolism, but the potential links have been explored more in rodents. Herein, we performed an hour-scale metabolomics analysis of serum and colonic digesta to characterize the circadian rhythmic metabolic patterns using a pig model under ad libitum feeding conditions. Importantly, our findings identified potential associations between colonic and body metabolism, revealing the potential relationships between colonic peptides and host appetite regulation. Concretely, amino acids accounted for the highest proportion in rhythmic serum metabolites, whereas lipids accounted for the highest proportion in rhythmic colonic metabolites. The diurnal difference analysis revealed that the levels of most amino acids and peptides were higher in the light phase, while the levels of most lipids were higher in the dark phase. And more correlations were be checked between serum amino acids, lipids, peptides and colonic metabolites in the light and more correlations were be checked between serum carbohydrates, cofactors and vitamins, energy, nucleotides, xenobiotics and colonic metabolites in the dark. Interestingly, peptides oscillated to a similar extent in serum and colonic digesta. Of note, colonic peptides composed of valine, proline and leucine were checked in positive associations to glucagon-like peptide-1 (GLP-1) in serum. And these peptides were positive with the genera Butyricicoccus, Streptococcus, Clostridioides, Bariatricus and Coriobacteriia_norank, and negative with Prevotella, and showed the potential relationships with colonic microbial biosynthesis of amino acids. Collectively, we mapped the rhythmic profiling on pig serum and colonic metabolites and revealed the relationships between host and gut metabolism. However, the underlying regulatory mechanisms remains to be further investigated.