Pivotal roles for pH, lactate and lactate-utilizing bacteria in the stability of a human colonic microbial ecosystem

Shui Ping Wang, Luis A. Rubio, Sylvia H. Duncan, Gillian E. Donachie, Grietje Holtrop, Galiana Lo, Freda M. Farquharson, Josef Wagner, Julian Parkhill, Petra Louis, Alan Walker* (Corresponding Author), Harry J. Flint

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

53 Citations (Scopus)
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Lactate can be produced by many gut bacteria, but in adults its accumulation in the colon is often an indicator of microbiota perturbation. Using continuous culture anaerobic fermentor systems, we found that lactate concentrations remained low in communities of human colonic bacteria maintained at pH 6.5, even when dl-lactate was infused at 10 or 20 mM. In contrast, lower pH (5.5) led to periodic lactate accumulation following lactate infusion in three fecal microbial communities examined. Lactate accumulation was concomitant with greatly reduced butyrate and propionate production and major shifts in microbiota composition, with Bacteroidetes and anaerobic Firmicutes being replaced by Actinobacteria, lactobacilli, and Proteobacteria Pure-culture experiments confirmed that Bacteroides and Firmicutes isolates were susceptible to growth inhibition by relevant concentrations of lactate and acetate, whereas the lactate-producer Bifidobacterium adolescentis was resistant. To investigate system behavior further, we used a mathematical model (microPop) based on 10 microbial functional groups. By incorporating differential growth inhibition, our model reproduced the chaotic behavior of the system, including the potential for lactate infusion both to promote and to rescue the perturbed system. The modeling revealed that system behavior is critically dependent on the proportion of the community able to convert lactate into butyrate or propionate. Communities with low numbers of lactate-utilizing bacteria are inherently less stable and more prone to lactate-induced perturbations. These findings can help us to understand the consequences of interindividual microbiota variation for dietary responses and microbiota changes associated with disease states. IMPORTANCE Lactate is formed by many species of colonic bacteria, and can accumulate to high levels in the colons of inflammatory bowel disease subjects. Conversely, in healthy colons lactate is metabolized by lactate-utilizing species to the short-chain fatty acids butyrate and propionate, which are beneficial for the host. Here, we investigated the impact of continuous lactate infusions (up to 20 mM) at two pH values (6.5 and 5.5) on human colonic microbiota responsiveness and metabolic outputs. At pH 5.5 in particular, lactate tended to accumulate in tandem with decreases in butyrate and propionate and with corresponding changes in microbial composition. Moreover, microbial communities with low numbers of lactate-utilizing bacteria were inherently less stable and therefore more prone to lactate-induced perturbations. These investigations provide clear evidence of the important role these lactate utilizers may play in health maintenance. These should therefore be considered as potential new therapeutic probiotics to combat microbiota perturbations.

Original languageEnglish
Article numbere00645-20
Number of pages18
Issue number5
Publication statusPublished - 8 Sept 2020

Bibliographical note

The authors would like to thank Donna Henderson for carrying out GC analysis, and Dr Helen Kettle for help with microPop. Thanks also to the Wellcome Sanger Institute’s core sequencing team and CGEBM at the University of Aberdeen for carrying out the Illumina MiSeq sequencing of 16S rRNA genes. The authors would also like to acknowledge the support of the Maxwell compute cluster funded by the University of Aberdeen.


  • Lactate
  • Lactate-utilizing bacteria
  • pH
  • Short chain fatty acids
  • Mathematical modelling
  • Short-chain fatty acids
  • PH
  • Mathematical modeling
  • lactate-utilizing bacteria
  • mathematical modeling
  • lactate
  • short-chain fatty acids
  • TOOL


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