ID: 2017-026 A method to increase animal lifespan by using bacterial methionine metabolism.
Principal Investigator: John Chaston
The effect of dietary restriction on Drosophila melanogaster (fruit fly) lifespan has been intensely studied. More recently, interest has grown in the microbiome's interaction with its host. This interaction has been shown to influence lifespan but the pathway by which this takes place is not known. Running a metagenome wide association study allowed the researchers at BYU to predict bacterial genes that were causing lifespan effects. After testing E. coli mutants, their predictions were confirmed that microbes were influencing Drosophila lifespan by altering flux through the transulfuration pathway.
The key discovery is that reducing the function of bacterial methionine metabolism genes (including E. coli: metE, metA, luxS, cobW, glyA) can extend the lifespan of animals associated with the mutant bacteria. The eliminating function of vitamin B6 genes in the bacteria decreases lifespan of the associated host. These findings are relevant to the passive production of methionine as well as to the creation of bacterial strains that are designed to actively consume methionine through increased transulfuration, for example by overexpression of cystathionine gamma lyase (CGL) and / or cystathionine beta synthase (CBS).
The researchers demonstrated that a bacterial strain that catabolizes methionine from the diet through transsulfuration decreases methionine content of the fly diet and the fly itself, and increases fly lifespan. A probiotic strain of Acetobacter that expresses bacterial CBS and CGL from K. variicola on a plasmid lowers the methionine content of fruit fly diet and extend D. melanogaster lifespan, relative to a strain that expresses no plasmid (‘control’, Fig 1A). Additionally, the methionine content of diets inoculated with the probiotic have lower methionine content than diets inoculated with the control strain, revealing that the bacteria lower the methionine content (Fig 1B). Together, these findings reveal a correlated effect of the probiotic strain on dietary methionine content and fly lifespan that is consistent with the effects of a fly fed on a methionine-restricted dietary regime. Our working model is that bacterial transsulfuration extends fruit fly lifespan by catabolizing some of the dietary methionine before the fly can consume it, effectively enacting a methionine restriction regime on the flies.
About the Market:
The invention could be used as a probiotic, and it could be especially useful if taken late in life. Companies are investing significantly in R&D activities for the development of efficient strains aimed at improving animal health. The probiotics global market (food & beverages, dietary supplements, animal feed) was estimated to be valued at $45.64 billion in 2017 and projected to grow at a CAGR of 7% to reach $64.02 billion by 2022 driven by the growing awareness about the benefits of probiotics among customers, rising demand for nutrient-rich feed for animals, and increasing demand for probiotic dietary supplements.
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