The role of lactate metabolism in shaping intestinal microbiota and health

Carlos Sabater; Xenia Vázquez; Sylvia H. Duncan; Carlos Sabater; Xenia Vázquez; Sylvia H. Duncan

doi:10.3934/microbiol.2026020

AIMS Microbiology

2026, Volume 12, Issue 3: 472-485. doi: 10.3934/microbiol.2026020

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Review

The role of lactate metabolism in shaping intestinal microbiota and health

1.
Rowett Institute, University of Aberdeen, Foresterhill, Aberdeen, Scotland, AB25 2ZD, UK
2.
Group of Functionality and Ecology of Beneficial Microorganisms (MicroHealth), Dairy Research Institute of Asturias (IPLA-CSIC), Francisco Pintado Fe nº 26, 33011, Oviedo, Asturias, Spain
3.
Health Research Institute of Asturias (ISPA), Avenida Hospital Universitario s/n, 33011 Oviedo, Asturias, Spain

Received: 03 February 2026 Revised: 30 June 2026 Accepted: 15 July 2026 Published: 23 July 2026

Lactate, particularly the D-isomer, which is produced exclusively by microbial fermentation, is usually low or undetectable in the healthy colon but can accumulate when there is a microbial imbalance, contributing to low pH and inflammation. Intestinal lactate-utilizing bacteria, such as Anaerobutyricum soehngenii, Anaerostipes species, and Coprococcus catus, convert lactate to short-chain fatty acids, including butyrate, potentially important for health. Here, we mined genomes of lactate utilizers for genes involved in propionate formation and conducted metabolic network modeling to investigate the cross-feeding mechanism. Genomes were also mined for antibiotic resistance genes, important when considering strains for biotherapeutics. Metabolic models were computed to elucidate the potential cross-feeding mechanisms between lactate utilizers in the human gut. Bioinformatics analysis revealed that the butyryl CoA:acetate CoA-transferase route was the dominant pathway for butyrate formation. The propanediol utilization compartment was annotated in A. halli, A. soehngenii, Eubacterium limosum, and C. catus. Of the genomes of key lactate utilizers assessed for antibiotic resistance genes, several possessed genes for multidrug resistance; however, other strains of Anaerostipes, C. catus, and Megasphaera elsdenii exhibited no antibiotic resistance genes. Metabolic modeling revealed that lactate-utilizing strains, including Anaerotignum, Eubacterium, and Anaerostipes, are key symbionts in maximizing the metabolic capabilities of the gut microbial community. Clinical interest in lactate-utilizers as next-generation probiotics is developing, and these data underscore the exciting therapeutic potential of targeting lactate metabolism to restore microbial and metabolic balance, in addition to potentially mitigating inflammatory diseases.
- lactate,
- probiotics,
- butyrate,
- propionate,
- Anaerobutyricum,
- microbial metabolism,
- gut health
Citation: Carlos Sabater, Xenia Vázquez, Sylvia H. Duncan. The role of lactate metabolism in shaping intestinal microbiota and health[J]. AIMS Microbiology, 2026, 12(3): 472-485. doi: 10.3934/microbiol.2026020

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Abstract

Lactate, particularly the D-isomer, which is produced exclusively by microbial fermentation, is usually low or undetectable in the healthy colon but can accumulate when there is a microbial imbalance, contributing to low pH and inflammation. Intestinal lactate-utilizing bacteria, such as Anaerobutyricum soehngenii, Anaerostipes species, and Coprococcus catus, convert lactate to short-chain fatty acids, including butyrate, potentially important for health. Here, we mined genomes of lactate utilizers for genes involved in propionate formation and conducted metabolic network modeling to investigate the cross-feeding mechanism. Genomes were also mined for antibiotic resistance genes, important when considering strains for biotherapeutics. Metabolic models were computed to elucidate the potential cross-feeding mechanisms between lactate utilizers in the human gut. Bioinformatics analysis revealed that the butyryl CoA:acetate CoA-transferase route was the dominant pathway for butyrate formation. The propanediol utilization compartment was annotated in A. halli, A. soehngenii, Eubacterium limosum, and C. catus. Of the genomes of key lactate utilizers assessed for antibiotic resistance genes, several possessed genes for multidrug resistance; however, other strains of Anaerostipes, C. catus, and Megasphaera elsdenii exhibited no antibiotic resistance genes. Metabolic modeling revealed that lactate-utilizing strains, including Anaerotignum, Eubacterium, and Anaerostipes, are key symbionts in maximizing the metabolic capabilities of the gut microbial community. Clinical interest in lactate-utilizers as next-generation probiotics is developing, and these data underscore the exciting therapeutic potential of targeting lactate metabolism to restore microbial and metabolic balance, in addition to potentially mitigating inflammatory diseases.

Acknowledgments

Carlos Sabater is funded by UKRI Engineering and Physical Sciences Research Council (EP/Z001064/1). Xenia Vázquez acknowledges her postdoctoral research contract ITM-POSTDOC-23-05 to ISPA. For the purpose of open access, the authors have applied a Creative Commons Attribution (CC BY) licence to any Author Accepted Manuscript version arising from this submission.

Conflicts of interest

The authors declare no conflict of interest.

Author contributions

Research conception: SHD and CS. Data analysis and figure configuration: CS and XV. Manuscript writing: CS, XV and SHD. Funding acquisition: CS and SHD. All authors reviewed and commented on the manuscript.

Data availability

Genomes used in Sheridan et al. [26] paper Distribution, organization and expression of genes concerned with anaerobic lactate utilization in human intestinal bacteria Microbial genomics https://doi.org/10.1099/mgen.0.000739.

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