Universität zu Köln

Davila Aleman, Francisco Daniel ORCID: 0000-0001-7636-2778 (2022). Microbiome and aging: A study of microbial evolution and community structure across model organisms. Abtract and Metadata. PhD thesis, Universität zu Köln.

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Abstract

Section I : Evolution of commensal gut microbes during host aging The animal intestine contains a large number of resident microorganisms (gut micro- biota), which has a significant impact on host physiology. The gut microbiota composition changes dramatically throughout the host lifespan as the gut microbes face multiple changes in their ecological niche. Age-associated changes in the host environment exert strong selective pressures on the microbial community, and whether and how gut microbes evolve during host life span and how this affects host age-associated phenotype is an open question. Specifically, novel genetic variants in the microbiome can confer new adaptive traits to the host or follow a virulent trajectory that affects host-microbiota homeostasis and delimit host lifespan. Previous studies demonstrated that the gut microbiome could rapidly adapt and evolve in a short timescale. However, less is known about the evolutionary dynamics of this complex microbial community during host aging within the same individual host. My research project aims to survey how the gut microbiota evolves during the host́s life span and whether evolutionary processes in the gut microbial communities affect microbial fitness. I leverage three different metagenomic sequencing strategies to reassemble more than 200 different metagenomic-assembled genomes from three different individual hosts. Using this genome catalog, I identified and tracked single- nucleotide variants that show signatures of selection during host life. Overall, I found that most new variants detected are impacted by purifying selection. However, I found that genetic variants in outer membrane proteins, carbohydrate-activate enzymes, and transposase genes show signatures of positive selection with no obvious beneficial effect on microbial fitness. The results obtained in this thesis will help understand the impact of host aging in determining microbiome evolution and whether evolution acts for the emergence of disease-promoting bacterial bacteria strains in the elderly. Section II: Characterization of the gut microbial community of the aging model Nothobranchius furzeri using short and long read metagenomics The African turquoise killifish (Nothobranchius furzeri) is an emerging model for aging research, thanks to its naturally short lifespan, easy husbandry under laboratory conditions, and the display of typical vertebrates hallmarks of aging. Recent work in this species has shown that gut microbiota transfer from young to middle-age killifish increases the recipients’ life span and delays age-related behavioral decline. The African turquoise killifish possesses a complex microbial diversity compared to other vertebrates (zebrafish, mouse, humans), which significantly decline during natural aging, with concurrent increase in the relative abundance of potentially pathogenic bacteria in older individuals. While the characterization of killifish-associated microbiota has focused on 16S amplicon sequencing, an account of the intestinal metagenome in this species is lacking. To fill this gap, I combine short-read with long-read sequencing technology to analyze the stool metagenome in captive turquoise killifish. I found that bacteria represent the majority of the stool microbiota (73%), with Proteobacteria as the most abundant Phylum (93%), followed by Actinobacteria (4%), Firmicutes (2%), and Bacteroidetes (2%). Viruses represent 0.04% of the total stool microbiome, followed by Archaea (0.02%) and Fungi (0.02%). Notably, 27% of the total stool metagenome does not map to any reference database (RefSeq) representing potentially novel host-associated species. Additionally, to generate a catalog of bacterial genomes associated with killifish gut, I assembled the genome of 8 of the most abundant bacterial species by culturing, isolating, sequencing, and hybrid assembly strategy, involving Illumina and long-read Nanopore sequencing technology. The analysis of the fully- assembled intestinal bacterial genomes revealed the presence of mobile elements, prophages, antibiotic-resistant genes, and other genetic elements that could potentially contribute to bacterial adaptations in the host. Together, metagenomics in the turquoise killifish represents a critical new resource for this species, which will help further develop this species as a naturally short-lived model to study host-microbiome interactions during aging.

Item Type:	Thesis (PhD thesis)
Creators:	Creators Email ORCID ORCID Put Code Davila Aleman, Francisco Daniel daniel.davila.aleman@gmail.com orcid.org/0000-0001-7636-2778 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-637479
Date:	25 April 2022
Language:	English
Faculty:	Faculty of Mathematics and Natural Sciences
Divisions:	CECAD - Cluster of Excellence Cellular Stress Responses in Aging-Associated Diseases
Subjects:	Natural sciences and mathematics Life sciences
Uncontrolled Keywords:	Keywords Language Aging English microbiome English microbial evolution English
Date of oral exam:	25 April 2022
Referee:	Name Academic Title Valenzano, Dario Prof. Dr.
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/63747