Tungsten is utilized for lactate consumption and SCFA production by a dominant human gut microbe <i>Eubacterium limosum</i>

<i>Eubacterium limosum</i> is a dominant member of the human gut microbiome and produces short-chain fatty acids (SCFAs). These promote immune system function and inhibit inflammation, making this microbe important for human health. Lactate is a primary source of gut SCFAs but its utilization by <i>E. limosum</i> has not been explored. We show that <i>E. limosum</i> growing on lactate takes up added tungstate rather than molybdate and produces the SCFAs acetate and butyrate, but not propionate. The genes encoding an electron bifurcating, tungsten-containing oxidoreductase (WOR1) and a tungsten-containing formate dehydrogenase (FDH), along with an electron bifurcating lactate dehydrogenase (LCT), lactate permease, and enzymes of the propanediol pathway, are all up-regulated on lactate compared to growth on glucose. Lactate metabolism is controlled by a GntR-family repressor (LctR) and two global regulators, Rex and CcpA, where Rex in part controls W storage and tungstopyranopterin (Tuco) biosynthesis. Tuco-dependent riboswitches, along with CcpA, also control two iron transporters, consistent with the increased iron demand for many iron-containing enzymes, including WOR1 and FDH, involved in SCFA production. From intracellular aldehyde concentrations and the substrate specificity of WOR1, we propose that WOR1 is involved in detoxifying acetaldehyde produced during lactate degradation. Lactate to SCFA conversion by <i>E. limosum</i> is clearly highly tungstocentric and tungsten might be an overlooked micronutrient in the human microbiome and in overall human health.

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Publication Details

Journal
Proceedings of the National Academy of Sciences
Published
2024-12-30
DOI
https://doi.org/10.1073/pnas.2411809121
Citations
9
Primary Topic
Gut microbiota and health
Type
article
Field-Weighted Citation Impact
2.10

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article

Tungsten is utilized for lactate consumption and SCFA production by a dominant human gut microbe Eubacterium limosum

Michael P. Thorgersen, Michael W. W. Adams, Nana Shao, Dmitry A. Rodionov et al.
9 citations
Proceedings of the National Academy of Sciences
Gut microbiota and health
2.10
article

Tungsten is utilized for lactate consumption and SCFA production by a dominant human gut microbe Eubacterium limosum

Michael P. Thorgersen, Michael W. W. Adams, Nana Shao, Dmitry A. Rodionov, Farris L. Poole, Gerrit J. Schut, Saisuki Putumbaka
article en
9 citations

Abstract

<i>Eubacterium limosum</i> is a dominant member of the human gut microbiome and produces short-chain fatty acids (SCFAs). These promote immune system function and inhibit inflammation, making this microbe important for human health. Lactate is a primary source of gut SCFAs but its utilization by <i>E. limosum</i> has not been explored. We show that <i>E. limosum</i> growing on lactate takes up added tungstate rather than molybdate and produces the SCFAs acetate and butyrate, but not propionate. The genes encoding an electron bifurcating, tungsten-containing oxidoreductase (WOR1) and a tungsten-containing formate dehydrogenase (FDH), along with an electron bifurcating lactate dehydrogenase (LCT), lactate permease, and enzymes of the propanediol pathway, are all up-regulated on lactate compared to growth on glucose. Lactate metabolism is controlled by a GntR-family repressor (LctR) and two global regulators, Rex and CcpA, where Rex in part controls W storage and tungstopyranopterin (Tuco) biosynthesis. Tuco-dependent riboswitches, along with CcpA, also control two iron transporters, consistent with the increased iron demand for many iron-containing enzymes, including WOR1 and FDH, involved in SCFA production. From intracellular aldehyde concentrations and the substrate specificity of WOR1, we propose that WOR1 is involved in detoxifying acetaldehyde produced during lactate degradation. Lactate to SCFA conversion by <i>E. limosum</i> is clearly highly tungstocentric and tungsten might be an overlooked micronutrient in the human microbiome and in overall human health.

Proceedings of the National Academy of SciencesVol. 122(1)
University of Georgia (US), Sanford Burnham Prebys Medical Discovery Institute (US), Discovery Institute (US)
Korea Advanced Institute of Science and Technology, National Institutes of Health, Directorate for Biological Sciences
Zero hunger
Openalex Percentile: Top 12%
Gut microbiota and health
2.10
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