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Title: Host-microbiota interactions in C. elegans : investigating the role of dietary glucose in the probiotic effects of Bacillus subtilis lacking ATP synthase
Author: Hauke Ancell, Henry James Frédéric de
ISNI:       0000 0004 7967 5114
Awarding Body: University of Warwick
Current Institution: University of Warwick
Date of Award: 2018
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The intestinal microbiota plays a critical role at the interface between nutrient uptake and host metabolism, and the bacterivorous nematode Caenorhabditis elegans presents a simple system in which to understand these interactions. The soil bacterium Bacillus subtilis enhances health and stress resistance in C. elegans compared to the standard diet of E. coli. Glucose is usually toxic to C. elegans, but a glycolysis-dependent B. subtilis 168 mutant lacking F₁F₀ ATP synthase (B. s.Δatp) extends lifespan by up to 40% in the presence of 2% D-glucose, compared to animals fed on the master strain (B. s. MS). Glucose does not affect the lifespan of C. elegans fed on B. s. MS. This work presents two sets of novel findings; first, C. elegans fed on B. s. Δatp in the absence (-Glu) and the presence (+Glu) of glucose displays characteristic signs of dietary restriction (DR), a highly conserved response to reduced nutrition without malnutrition. B. s. Δatp(-Glu) delays development, improves health without longevity and regulates DR-related genes including PHA-4/FOXA. Extensive sporulation of B. s. Δatp(-Glu) appears to contribute to these phenotypes. In response to glucose, this diet develops a rudimentary biofilm which is likely to obstruct feeding and underlie a coordinated DR response - including larval arrest, small body size, longevity and delayed egg laying. Second, when these issues are overcome by limiting biofilm development and preventing bacterial sporulation, the mutant diet improves lifespan and health in C. elegans probably through a separate mechanism that is not yet identified. These findings demonstrate that microbial metabolism can dramatically alter the effects of dietary glucose on host physiology and highlight important challenges associated with the provision of non-standard diets to C. elegans. Moreover, this diet-mediated uncoupling of lifespan from health and stress resistance offers an opportunity to uncover conserved molecular determinants of sustained health.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: QL Zoology