Distribution, organization and expression of genes concerned with anaerobic lactate utilization in human intestinal bacteria.

Lactate accumulation in the human gut is linked to a range of deleterious health impacts. However, lactate is consumed and converted to the beneficial short-chain fatty acids butyrate and propionate by indigenous lactate-utilizing bacteria. To better understand the underlying genetic basis for lactate utilization, transcriptomic analyses were performed for two prominent lactate-utilizing species from the human gut, and , during growth on lactate, hexose sugar or hexose plus lactate. In L2-7 six genes of the lactate utilization () cluster, including NAD-independent d-lactate dehydrogenase (d-iLDH), were co-ordinately upregulated during growth on equimolar d- and l-lactate (dl-lactate). Upregulated genes included an acyl-CoA dehydrogenase related to butyryl-CoA dehydrogenase, which may play a role in transferring reducing equivalents between reduction of crotonyl-CoA and oxidation of lactate. Genes upregulated in GD/7 included a six-gene cluster () encoding propionyl CoA-transferase, a putative lactoyl-CoA epimerase, lactoyl-CoA dehydratase and lactate permease, and two unlinked acyl-CoA dehydrogenase genes that are candidates for acryloyl-CoA reductase. A d-iLDH homologue in is encoded by a separate, partial gene cluster, but not upregulated on lactate. While converts three mols of dl-lactate via the acrylate pathway to two mols propionate and one mol acetate, some of the acetate can be re-used with additional lactate to produce butyrate. A key regulatory difference is that while glucose partially repressed cluster expression in , there was no repression of lactate-utilization genes by fructose in the non-glucose utilizer . This suggests that these species could occupy different ecological niches for lactate utilization in the gut, which may be important factors to consider when developing lactate-utilizing bacteria as novel candidate probiotics.