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Molecular Biotechnology

, Volume 61, Issue 1, pp 1–11 | Cite as

Ferulic Acid Produced by Lactobacillus fermentum Influences Developmental Growth Through a dTOR-Mediated Mechanism

  • Susan Westfall
  • Nikita Lomis
  • Satya PrakashEmail author
Original Paper

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.

Keywords

Lactobacillus fermentum Ferulic acid TOR Drosophila melanogaster Probiotics Gut microbiota Diabetes 

Notes

Funding

This work was supported by NSERC and CIHR.

Compliance with Ethical Standards

Conflict of interest

This publication includes data filed in a US provisional patent (62/629832) through a company which SW and SP are co-founders. The authors received no funding from the company for completing this work.

Supplementary material

12033_2018_119_MOESM1_ESM.pdf (89 kb)
Supplementary material 1 (PDF 89 KB)
12033_2018_119_MOESM2_ESM.docx (43 kb)
Supplementary material 2 (DOCX 43 KB)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Biomedical Technology and Cell Therapy Research Laboratory, Department of Biomedical Engineering, Faculty of MedicineMcGill UniversityMontrealCanada

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