Transkingdom interactions between Lactobacilli and hepatic mitochondria attenuate western diet-induced diabetes

Richard R. Rodrigues, Manoj Gurung, Zhipeng Li, Manuel García-Jaramillo, Renee Greer, Christopher Gaulke, Franziska Bauchinger, Hyekyoung You, Jacob W. Pederson, Stephany Vasquez-Perez, Kimberly D. White, Briana Frink, Benjamin Philmus, Donald B. Jump, Giorgio Trinchieri, David Berry, Thomas J. Sharpton, Amiran Dzutsev, Andrey Morgun () and Natalia Shulzhenko ()
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Richard R. Rodrigues: Oregon State University
Manoj Gurung: Oregon State University
Zhipeng Li: Oregon State University
Manuel García-Jaramillo: Oregon State University
Renee Greer: Oregon State University
Christopher Gaulke: Oregon State University
Franziska Bauchinger: University of Vienna
Hyekyoung You: Oregon State University
Jacob W. Pederson: Oregon State University
Stephany Vasquez-Perez: Oregon State University
Kimberly D. White: Oregon State University
Briana Frink: Oregon State University
Benjamin Philmus: Oregon State University
Donald B. Jump: Oregon State University
Giorgio Trinchieri: National Institutes of Health
David Berry: University of Vienna
Thomas J. Sharpton: Oregon State University
Amiran Dzutsev: National Institutes of Health
Andrey Morgun: Oregon State University
Natalia Shulzhenko: Oregon State University

Nature Communications, 2021, vol. 12, issue 1, 1-15

Abstract: Abstract Western diet (WD) is one of the major culprits of metabolic disease including type 2 diabetes (T2D) with gut microbiota playing an important role in modulating effects of the diet. Herein, we use a data-driven approach (Transkingdom Network analysis) to model host-microbiome interactions under WD to infer which members of microbiota contribute to the altered host metabolism. Interrogation of this network pointed to taxa with potential beneficial or harmful effects on host’s metabolism. We then validate the functional role of the predicted bacteria in regulating metabolism and show that they act via different host pathways. Our gene expression and electron microscopy studies show that two species from Lactobacillus genus act upon mitochondria in the liver leading to the improvement of lipid metabolism. Metabolomics analyses revealed that reduced glutathione may mediate these effects. Our study identifies potential probiotic strains for T2D and provides important insights into mechanisms of their action.

Date: 2021
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DOI: 10.1038/s41467-020-20313-x

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