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

15 Citations (Scopus)

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
Article number000739
Number of pages18
JournalMicrobial Genomics
Volume8
Issue number1
Early online date25 Jan 2022
DOIs
Publication statusPublished - Jan 2022

Bibliographical note

Funding information
PL, SHD, HJF, AWW and the Rowett Institute received core financial support from the Scottish Government Rural and Environmental Sciences and Analytical Services (SG674 RESAS). The work was also partly funded by Chr. Hansen, a global bioscience company that develops natural ingredient solutions for the food, nutritional, pharmaceutical and agricultural industries, who supported POS and ET. Chr. Hansen exerted no influence on results obtained and presented in this manuscript. This also does not alter our adherence to Microbial Genomics’
policies on sharing data and materials.
Acknowledgements

The authors would like to thank Donna Henderson (Rowett Institute, University of Aberdeen) for carrying out gas chromatography analysis of short-chain fatty acids, and also thank the Centre for Genome-Enabled Biology and Medicine (CGEBM) at the University of Aberdeen for carrying out the Illumina-based transcriptomics sequencing. We would also like to acknowledge the support of the Maxwell computer cluster funded by the University of Aberdeen.

Data Availability Statement

All supporting data, code and protocols have been provided within the article or through supplementary data files. Eighteen supplementary tables and one supplementary figure are available with the online version of this article.

Novel draft genomes generated for this study have been made available from GenBank (https://www.ncbi.nlm.nih.gov/bioproject/) under BioProject number PRJNA701799. RNA-seq data have been deposited in the ArrayExpress database at EMBL-EBI (www. ebi.ac.uk/arrayexpress) under accession number E-MTAB-10136. Further details of additional existing genomic data that were analysed in this project are given in Tables 1 and S2 (available in the online version of this article), and at https://github.com/ SheridanPO/Lactate-utilizing-bacteria. Supplementary Material can be found in Figshare: https://doi.org/10.6084/m9.figshare.16510344.v1[1].

Keywords

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

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