The gut mycobiome and healthy ageing: signatures of longevity and the effects of probiotic intervention

Scientific excellence

Recent evidence suggests that gut microbiome-targeted interventions may have therapeutic potential in age-related diseases, for retarding aspects of the ageing process, and in promoting longevity1. Healthy human centenarians have gut microbiome profiles that may be predictors of longevity2,3. An increase in the representation of bacterial species such as Akkermansia and Bifidobacterium within the aging gut microbiome has been specifically identified as a microbial signature of longevity, and suggests a potential target for therapeutic intervention as targeted modulation of gut microbiome composition could promote healthy ageing2,3. Interestingly, many of these ‘signature’ bacteria are promoted as probiotics and suggested to provide health benefits. A number of mechanisms by which the gut microbiome may favourably impact health and ageing have been investigated. For example, feeding mice with Bifidobacterium animalis isolated from the gut of centenarians has been found to improve a number of parameters typically related to ageing in those animals4. It is therefore possible that the isolation of gut microorganisms associated with exceptional longevity, and the development of probiotic interventions utilising such cultures, may have potential in terms of promoting ‘health-span’ and lifespan1. In terms of the analysis of the human gut microbiota, the focus to date has been overwhelmingly on the composition of the bacterial component, despite the fact that fungi are also an integral part of the gut microbiome. Accordingly, while bacteria have been intensively studied, little is known about the nature of the gut fungal community (mycobiome). Recent studies have highlighted that the gut mycobiome is much more diverse and abundant than previously thought, and there is increasing evidence of significant roles that fungi play in host homeostasis, and of their interactions with gut bacteria5. Given the growing challenges posed by an aging human population novel solutions are urgently needed, and a state-of-the–art investigation into the nature of our natural mycobiome, and its potential to influence on our health and lifespan, is thus both a fascinating and very timely subject. It offers considerable potential in terms of development of novel therapeutic interventions, easily warranting further study and increased public awareness.

Aim

To analyse gut mycobiome composition across a wide age-range of volunteers and identify potential fungal signatures of longevity and determine their probiotic potential. We will also establish an in vitro model of the human gut to assess interactions between gut fungi and other members of the gut microbiome in close-to-real situations.

Methodology

The mycobiome in faecal samples from a wide age-range of volunteers will be characterised using ITS1/ITS2-based deep-sequencing approaches6,7. The probiotic potential of fungal strains associated with longevity, isolated from those samples, will be assessed using standard methods8. An innovative in vitro model of the human gut will be engineered9, and challenged with fungal isolates to monitor their interaction with the remaining microbiome under distinct reproducible conditions.

Strategic relevance

The project brings together multidisciplinary and intersectoral partners with the aim of promoting healthy ageing, thereby generating considerable impact and value to society, and thus realising the strategic Healthy Futures vision of the University of Brighton.

Interdisciplinarity and fit with relevant DTA programme

The project will identify mycobiome signatures of longevity, and reveal possible probiotic interventions with potential to promote healthy ageing, aligning perfectly with the DTA programme. The PhD candidate will have access to a range of academic and industrial environments, and interdisciplinary expertise including: conventional and molecular microbiology (including metagenomics and metaproteomics) [JIS, LB, CE], bioinformatics [CE], and statistics [FG], needed to unveil the diversity of the gut mycobiome; probiotic interventions and industrial formulations [SP], to study the probiotic potential of gut fungi; and gut physiology [SB, FG] and engineering/modelling [SB], to develop an innovative in vitro human gut model

Applications

Applicants must apply using the online form on the University Alliance website at https://unialliance.ac.uk/dta/cofund/how-to-apply/. Full details of the programme, eligibility details and a list of available research projects can be seen at https://unialliance.ac.uk/dta/cofund/

The final deadline for application is Monday 8 October 2018. There will be another opportunity to apply for DTA3 projects in the spring of 2019. The list of available projects is likely to change for the second intake.