Catalyst Awardee

Project Description

Unraveling the Mycobiome: Fungi as a novel class of probiotics to target inflammaging

Douglas Kiel, MD, MPH; Shivani Sahni, PhD; and Eric Schott, PhD,

Competition Sponsor: US National Academy of Medicine

An aging population has led to a significant global increase in age-related diseases including cardiovascular disease, Alzheimer’s, and others. At the core of this is chronic low-grade inflammation known as inflammaging, and recent evidence describes the gut microbiome as a key regulator of the inflammaging process through direct impact on immune system development and function. Studies have demonstrated the efficacy of probiotic bacteria in treating inflammatory disorders through several biological processes (epigenetic alteration, mitochondrial dysfunction, others) known as hallmarks of aging. While the impact bacteria have on the immune system and human health is well described, fungi, a major component of the gut microbiome (mycobiome) have been largely overlooked due to multiple factors including fungi’s large, complex genomes that require deep sequencing and a hybrid assembly, lack of fungal genome databases for functional gene prediction, and underdeveloped bioinformatic tools to identify fungal metabolites important to human health. We hypothesize the mycobiome could offer a large, untapped reservoir of probiotic fungi with the ability to combat inflammaging. Given this, we propose to sequence a subset of our fungal collection with Nanopore technology and develop bioinformatic tools to complete hybrid assembly, annotation, and gene prediction to identify fungi with probiotic potential. Further, we will assess candidate strains with in vitro cell culture systems to identify fungi with anti-inflammatory properties to be tested in vivo. Here, we have the opportunity to discover safe and novel fungal agents and open an entirely new class of probiotics to specifically reduce inflammaging and related chronic illness.

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