Ferulic Acid Produced by Lactobacillus Fermentum Influences Developmental Growth Through a DTOR-Mediated Mechanism

Overview

Journal Mol Biotechnol

Publisher Springer

Specialties Biotechnology
Molecular Biology

Date 2018 Oct 29

PMID 30368647

Citations 11

Authors

Susan Westfall

Nikita Lomis

Satya Prakash

Affiliations

Soon will be listed here.

Abstract

The composition and activity of the gut microbiota impacts several energy-regulating conditions including diabetes, obesity and metabolic syndrome; however, the specific mechanisms linking the gut microbiota with the host's energy homeostasis remain elusive. Probiotics are health-promoting bacteria that when consumed, alter the composition and/or metabolism of resident microbiota conferring health benefits. To assess the role of a specific probiotic treatment on microbiota-derived impacts on energy homeostasis in the context of development, Drosophila melanogaster larvae were orally administered the probiotic Lactobacillus fermentum NCIMB 5221 or its metabolic product, ferulic acid: a potent anti-inflammatory and anti-oxidant hydroxycinnamic acid. In Drosophila larvae, both the probiotic and metabolite treatments advanced the nutritionally dependent stages of development in a dose-dependent manner while not affecting the hormonally controlled pupariation stage. These treatments correspondingly accelerated the developmental phase-dependent 20-hydroxyecdysone and insulin receptor gene expression surges and altered the phasic expression of downstream insulin signalling factors including dAkt, dTOR and dFOXO indicating a deep level of nutritionally dependent regulatory control. Administering Drosophila both ferulic acid and the TOR inhibitor rapamycin eliminated the physiological and molecular developmental advances indicating that microbial ferulic acid affects energy utilization in a dTOR-dependent manner outlining a potential mechanism of action of L. fermentum NCIMB 5221 on modulating microbiota dynamics to modulate energy homeostasis. TOR conservation from flies to humans indicates that probiotic therapy with L. fermentum NCIMB 5221 has a high therapeutic potential towards several human energy regulatory diseases such as obesity, diabetes and cancer.

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References

Brogiolo W, Stocker H, Ikeya T, RINTELEN F, Fernandez R, Hafen E . An evolutionarily conserved function of the Drosophila insulin receptor and insulin-like peptides in growth control. Curr Biol. 2001; 11(4):213-21. DOI: 10.1016/s0960-9822(01)00068-9. View

Kramer J, Davidge J, Lockyer J, Staveley B . Expression of Drosophila FOXO regulates growth and can phenocopy starvation. BMC Dev Biol. 2003; 3:5. PMC: 183841. DOI: 10.1186/1471-213X-3-5. View

Puig O, Marr M, Ruhf M, Tjian R . Control of cell number by Drosophila FOXO: downstream and feedback regulation of the insulin receptor pathway. Genes Dev. 2003; 17(16):2006-20. PMC: 196255. DOI: 10.1101/gad.1098703. View

Wheeler D, Nijhout H . A perspective for understanding the modes of juvenile hormone action as a lipid signaling system. Bioessays. 2003; 25(10):994-1001. DOI: 10.1002/bies.10337. View

Broughton S, Piper M, Ikeya T, Bass T, Jacobson J, Driege Y . Longer lifespan, altered metabolism, and stress resistance in Drosophila from ablation of cells making insulin-like ligands. Proc Natl Acad Sci U S A. 2005; 102(8):3105-10. PMC: 549445. DOI: 10.1073/pnas.0405775102. View

Shingleton A, Das J, Vinicius L, Stern D . The temporal requirements for insulin signaling during development in Drosophila. PLoS Biol. 2005; 3(9):e289. PMC: 1184592. DOI: 10.1371/journal.pbio.0030289. View

Colombani J, Bianchini L, Layalle S, Pondeville E, Dauphin-Villemant C, Antoniewski C . Antagonistic actions of ecdysone and insulins determine final size in Drosophila. Science. 2005; 310(5748):667-70. DOI: 10.1126/science.1119432. View

Warren J, Yerushalmi Y, Shimell M, OConnor M, Restifo L, Gilbert L . Discrete pulses of molting hormone, 20-hydroxyecdysone, during late larval development of Drosophila melanogaster: correlations with changes in gene activity. Dev Dyn. 2005; 235(2):315-26. PMC: 2613944. DOI: 10.1002/dvdy.20626. View

Wullschleger S, Loewith R, Hall M . TOR signaling in growth and metabolism. Cell. 2006; 124(3):471-84. DOI: 10.1016/j.cell.2006.01.016. View

10.

Ley R, Peterson D, Gordon J . Ecological and evolutionary forces shaping microbial diversity in the human intestine. Cell. 2006; 124(4):837-48. DOI: 10.1016/j.cell.2006.02.017. View

11.

Turnbaugh P, Ley R, Mahowald M, Magrini V, Mardis E, Gordon J . An obesity-associated gut microbiome with increased capacity for energy harvest. Nature. 2006; 444(7122):1027-31. DOI: 10.1038/nature05414. View

12.

Backhed F, Manchester J, Semenkovich C, Gordon J . Mechanisms underlying the resistance to diet-induced obesity in germ-free mice. Proc Natl Acad Sci U S A. 2007; 104(3):979-84. PMC: 1764762. DOI: 10.1073/pnas.0605374104. View

13.

Cani P, Hoste S, Guiot Y, Delzenne N . Dietary non-digestible carbohydrates promote L-cell differentiation in the proximal colon of rats. Br J Nutr. 2007; 98(1):32-7. DOI: 10.1017/S0007114507691648. View

14.

Hietakangas V, Cohen S . Re-evaluating AKT regulation: role of TOR complex 2 in tissue growth. Genes Dev. 2007; 21(6):632-7. PMC: 1820936. DOI: 10.1101/gad.416307. View

15.

Mirth C, Riddiford L . Size assessment and growth control: how adult size is determined in insects. Bioessays. 2007; 29(4):344-55. DOI: 10.1002/bies.20552. View

16.

Giannakou M, Partridge L . Role of insulin-like signalling in Drosophila lifespan. Trends Biochem Sci. 2007; 32(4):180-8. DOI: 10.1016/j.tibs.2007.02.007. View

17.

Salih D, Brunet A . FoxO transcription factors in the maintenance of cellular homeostasis during aging. Curr Opin Cell Biol. 2008; 20(2):126-36. PMC: 2387118. DOI: 10.1016/j.ceb.2008.02.005. View

18.

Layalle S, Arquier N, Leopold P . The TOR pathway couples nutrition and developmental timing in Drosophila. Dev Cell. 2008; 15(4):568-77. DOI: 10.1016/j.devcel.2008.08.003. View

19.

Grewal S . Insulin/TOR signaling in growth and homeostasis: a view from the fly world. Int J Biochem Cell Biol. 2008; 41(5):1006-10. DOI: 10.1016/j.biocel.2008.10.010. View

20.

Murphy E, Cotter P, Healy S, Marques T, OSullivan O, Fouhy F . Composition and energy harvesting capacity of the gut microbiota: relationship to diet, obesity and time in mouse models. Gut. 2010; 59(12):1635-42. DOI: 10.1136/gut.2010.215665. View