Gut microbe-derived lactic acid optimizes host energy metabolism during starvation
Millington, J. W.; Lopez, J. A.; Sajjadian, A. M.; Scheffler, R. J.; DeFelice, B. C.; Ludington, W. B.; Good, B. H.; O'Brien, L. E.; Huang, K. C.
Show abstract
Gut microbes convert dietary compounds into an array of metabolites that can directly provide energy to their host and indirectly impact host metabolism as systemic endocrine signals. Here, we show that gut microbe-derived metabolites can extend Drosophila melanogaster survival during starvation, despite minimal alteration of dietary energy intake. Combining survival assays with mathematical modeling and untargeted metabolomics, we identify a single, dominant mediator of starvation resilience: lactic acid produced by the commensal bacterium Lactiplantibacillus plantarum. We discover that the basis of starvation resilience is not catabolism of lactic acid using lactate dehydrogenase, but rather increased dietary energy yield through lactic acid-driven promotion of oxidative phosphorylation. Our findings emphasize the role of the microbiome as a source of endocrine cues coordinating host metabolism and underscore the potential of microbiome-derived metabolites as therapeutic molecules for manipulating metabolic health and preventing disease.
Matching journals
The top 3 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Intestinal GCN2 controls Drosophila systemic growth in response to Lactiplantibacillus plantarum symbiotic cues encoded by r/tRNA operons 95%
- Metabolite plasticity drives carbon-nitrogen resource budgeting to enable division of labor in a clonal community 95%
- Taste triggers a homeostatic temperature control in hungry flies 95%
Similar papers in this journal
- Developmental function and state transitions of a gene expression oscillator in C. elegans 94%
- Evaluating the Simple Arrhenius Equation for the Temperature Dependence of Complex Developmental Processes 93%
- Dormancy-to-death transition in yeast spores occurs due to gradual loss of gene-expressing ability 93%
Similar papers in this journal
- Behavior choices amongst grooming, feeding, and courting in Drosophila show contextual flexibility, not an absolute hierarchy of needs 94%
- Displacement experiments provide evidence for path integration in Drosophila 94%
- Social foraging extends associative odor-food memory expression in an automated learning assay for Drosophila melanogaster 94%
Similar papers in this journal
- Metabolic cross-feeding allows a gut microbial community to overcome detrimental diets and alter host behaviour 96%
- Neurofibromin regulates metabolic rate via neuronal mechanisms in Drosophila 94%
- Nutritional vitamin B12 regulates RAS/MAPK-mediated cell fate decisions through the one-carbon metabolism 94%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.