Description:
<jats:p>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, <jats:italic>
<jats:named-content content-type="species">
<jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="http://doi.org/10.1601/nm.33224" xlink:type="simple">Anaerobutyricum soehngenii</jats:ext-link>
</jats:named-content>
</jats:italic> and <jats:italic>
<jats:named-content content-type="species">
<jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="http://doi.org/10.1601/nm.4139" xlink:type="simple">Coprococcus catus</jats:ext-link>
</jats:named-content>
</jats:italic>, during growth on lactate, hexose sugar or hexose plus lactate. In <jats:italic>
<jats:named-content content-type="species">
<jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="http://doi.org/10.1601/nm.33224" xlink:type="simple">A. soehngenii</jats:ext-link>
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</jats:italic> L2-7 six genes of the lactate utilization (<jats:italic>lct</jats:italic>) cluster, including NAD-independent <jats:sc>d</jats:sc>-lactate dehydrogenase (<jats:sc>d</jats:sc>-iLDH), were co-ordinately upregulated during growth on equimolar <jats:sc>d</jats:sc>- and <jats:sc>l</jats:sc>-lactate (<jats:sc>dl</jats:sc>-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 <jats:italic>
<jats:named-content content-type="species">
<jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="http://doi.org/10.1601/nm.4139" xlink:type="simple">C. catus</jats:ext-link>
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</jats:italic> GD/7 included a six-gene cluster (<jats:italic>lap</jats:italic>) encoding propionyl CoA-transferase, a putative lactoyl-CoA epimerase, lactoyl-CoA dehydratase and lactate permease, and two unlinked acyl-CoA dehydrogenase genes that are candidates for acryloyl-CoA reductase. A <jats:sc>d</jats:sc>-iLDH homologue in <jats:italic>
<jats:named-content content-type="species">
<jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="http://doi.org/10.1601/nm.4139" xlink:type="simple">C. catus</jats:ext-link>
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</jats:italic> is encoded by a separate, partial <jats:italic>lct,</jats:italic> gene cluster, but not upregulated on lactate. While <jats:italic>
<jats:named-content content-type="species">
<jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="http://doi.org/10.1601/nm.4139" xlink:type="simple">C. catus</jats:ext-link>
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</jats:italic> converts three mols of <jats:sc>dl</jats:sc>-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 <jats:italic>lct</jats:italic> cluster expression in <jats:italic>
<jats:named-content content-type="species">
<jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="http://doi.org/10.1601/nm.33224" xlink:type="simple">A. soehngenii</jats:ext-link>
</jats:named-content>
</jats:italic>, there was no repression of lactate-utilization genes by fructose in the non-glucose utilizer <jats:italic>
<jats:named-content content-type="species">
<jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="http://doi.org/10.1601/nm.4139" xlink:type="simple">C. catus</jats:ext-link>
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</jats:italic>. 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.</jats:p>