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

Paul Sheridan, Petra Louis, Eleni Tsompanidou, Sophie Shaw, Hermie J. M. Harmsen, Sylvia Duncan, Harry J. Flint, Alan Walker* (Corresponding Author)

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

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, Anaerobutyricum soehngenii and Coprococcus catus, during growth on lactate, hexose sugar, or hexose plus lactate. In A. soehngenii L2-7 six genes of the lactate utilization (lct) cluster, including NAD-independent D-lactate dehydrogenase (i-LDH), 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 C. catus GD/7 included a six-gene cluster (lap) encoding propionyl CoA-transferase, a putative lactoyl35 CoA epimerase, lactoyl-CoA dehydratase and lactate permease, and two unlinked acyl-CoA dehydrogenase genes that are candidates for acryloyl-CoA reductase. An i-LDH homolog in
C. catus is encoded by a separate, partial lct, gene cluster, but not upregulated on lactate. While C. catus 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 lct cluster expression in A. soehngenii, there was no repression of lactate utilization genes by fructose in the non-glucose utilizer C. catus. 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.
Original languageEnglish
JournalMicrobial Genomics
Publication statusAccepted/In press - 2 Nov 2021

Keywords

  • Human gut microbiota
  • lactate-utilizing bacteria
  • anaerobic metabolism
  • upregulation by lactate
  • transcriptomics

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