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

Paul O. Sheridan, Petra Louis, Eleni Tsompanidou, Sophie Shaw, Hermie J. Harmsen, Sylvia H. Duncan, Harry J. Flint, Alan W. Walker*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

2 Citations (Scopus)
14 Downloads (Pure)

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 (Ict) 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 C. catus GD/7 included a six-gene cluster (lap) encoding propionyl CoA-transferase, a putative lactoyl-CoA, epimerase, lactoylCoA dehydratase and lactate permease, and two unlinked acyl-CoA dehydrogenase genes that are candidates for acryloyl-CoA reductase. A D-iLDH homologue in C. catus is encoded by a separate, partial 10, gene cluster, but not upregulated on lactate. While C. catus converts three mots of DL-lactate via the acrylate pathway to two mots 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
Article number000739
Number of pages18
JournalMicrobial genomics
Volume8
Issue number1
Early online date25-Jan-2022
DOIs
Publication statusPublished - 2022

Keywords

  • Human gut microbiota
  • lactate utilizing bacteria
  • anaerobic metabolism
  • upregulation by lactate
  • transcriptomics
  • BUTYRATE-PRODUCING BACTERIA
  • NADP-REDUCING HYDROGENASE
  • MEGASPHAERA-ELSDENII
  • COMB. NOV.
  • METABOLISM
  • RUMEN
  • FERMENTATION
  • COA
  • PROPIONATE
  • ALIGNMENT

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