Mesenteric lymph system constitutes the second route in gut-liver axis and transports metabolism-modulating gut microbial metabolites

The gut-liver axis denotes the intricate connection and interaction between gut microbiome and liver, in which compositional and functional shifts in gut microbiome affect host metabolism. Hepatic portal vein of the blood circulation system has been thought to be the major route for metabolite transportation in the gut-liver axis, but the existence and importance of other routes remain elusive. Here, we perform metabolome comparison in blood circulation and mesenteric lymph systems and identify significantly shifted metabolites in serum and mesentery. Using cellular assays, we find that the majority of decreased metabolites in lymph system under high-fat diet are effective in alleviating metabolic disorders, indicating a high potential of lymph system in regulating liver metabolism. Among those, a representative metabolite, L-carnitine, reduces diet-induced obesity in mice. Metabolic tracing analysis identifies that L-carnitine is independently transported by the mesenteric lymph system, serving as an example that lymph circulation comprises a second route in the gut-liver axis to modulate liver metabolism. Our study provides new insights into metabolite transportation via mesenteric lymph system in the gut-liver axis, offers an extended scope for the investigations in host-gut microbiota metabolic interactions and potentially new targets in the treatment of metabolic disorders.

The role of gut microbiota associated metabolites in digestive disorders

The gut has been a focal point in the research of digestive system disorders.The internal microbiota generates metabolites that function as signaling molecules and substrates,interacting with the intestinal wall and influ-encing host physiology and pathology.Besides,the gut microbiota and metabolites owe highly diverse types and quantities,posing challenges for quantitative analysis,and monitoring frequent interactions between diges-tive tract metabolites and the intestinal wall remains a challenge.However,research targeting gut microbiota metabolites has elucidated their relevance to digestive diseases.By modulating metabolites such as short-chain fatty acids,bile acids,and lipopolysaccharides,it is possible to intervene in the progression of diseases such as inflammatory bowel disease and non-alcoholic fatty liver disease.Currently,research on gut microbiota is advancing,and more work is required to explore the interactions between host,microbes and underlying mech-anisms.In this review,we have revisited the generation of gut microbiota-related metabolites,their impact on diseases,and modes of interaction,emphasizing the significant role of metabolites in digestive system disorders.It is believed that the linkage between gut microbiota and diseases in current research can be established through metabolites,providing a framework and foundation for research in the field of metabolomics and fundamental mechanisms.