Gut lactate increases circulating L-Lac-Phe and key metabolites linked to GLP-1 and human health.

Lactate, a small organic acid related to short-chain fatty acids (SFCAs), is emerging as a key energy metabolite, although much remains unknown about its actions in the gut. In the current study, we specifically tested how oral (PO) and parenteral (IV) lactate affects lactoylation of amino acids (Lac-AA) in humans and whether these clinical results could be reproduced in a perfused rat intestine model. Furthermore, using targeted and untargeted metabolomics we globally investigated how PO and IV lactate impact the circulating metabolome to delineate potential circulating messengers and obtain additional mechanistic insight into how oral lactate may potentially induce GLP-1 secretion as well as alternative metabolites correlated to human health. Our findings provide a better understanding of the general effects of lactate in the gut and how it potentially signals to increase satiety in humans.