Metabolomic alteration in the mouse distal colonic mucosa after oral gavage with oxalobacter formigenes

Abstract

Oxalobacter formigenes has been investigated for years due to its proposed ability to produce a secretagogue compound that initiates net intestinal oxalate secretion, thereby theoretically reducing circulating oxalate and risk of kidney stone formation. Strains which have been shown to exhibit this function in vivo across native tissue include the human strain, HC1, and the wild rat strain, OxWR. While previous work on these secretagogue-relevant strains has focused on profiling their metabolome and lipidome in vitro, efforts to characterize their influence on host intestinal mucosal biochemistry in vivo are yet to be reported. Much work has been done over the years with O. formigenes in relation to the secretagogue hypothesis, but it has never been clearly demonstrated that this microorganism is capable of inducing metabolic changes in native host tissue, which would be expected with the production of a transport-inducing compound. In this work, we show how the distal colonic mucosal metabolomic profile in a mouse model exhibited significant changes in the levels of a variety of metabolites as a result of oral gavage with O. formigenes HC1. Among these significant metabolites was nicotinic acid, an essential nutrient shown in past work to be produced in the gut by the native microbiome. Our finding that the in vivo biochemical state of the distal colon was altered with O. formigenes lends support to the secretagogue hypothesis and serves as a pioneering step in characterizing the biochemical interplay between O. formigenes and the mammalian host.