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Microbial Genetic Composition Tunes Host Longevity.

ABSTRACT: Homeostasis of the gut microbiota critically influences host health and aging. Developing genetically engineered probiotics holds great promise as a new therapeutic paradigm to promote healthy aging. Here, through screening 3,983 Escherichia coli mutants, we discovered that 29 bacterial genes, when deleted, increase longevity in the host Caenorhabditis elegans. A dozen of these bacterial mutants also protect the host from age-related progression of tumor growth and amyloid-beta accumulation. Mechanistically, we discovered that five bacterial mutants promote longevity through increased secretion of the polysaccharide colanic acid (CA), which regulates mitochondrial dynamics and unfolded protein response (UPRmt) in the host. Purified CA polymers are sufficient to promote longevity via ATFS-1, the host UPRmt-responsive transcription factor. Furthermore, the mitochondrial changes and longevity effects induced by CA are conserved across different species. Together, our results identified molecular targets for developing pro-longevity microbes and a bacterial metabolite acting on host mitochondria to promote longevity.

SUBMITTER: Han B

PROVIDER: S-EPMC5635830 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Microbial Genetic Composition Tunes Host Longevity.

Han Bing B Sivaramakrishnan Priya P Lin Chih-Chun J CJ Neve Isaiah A A IAA He Jingquan J Tay Li Wei Rachel LWR Sowa Jessica N JN Sizovs Antons A Du Guangwei G Wang Jin J Herman Christophe C Wang Meng C MC

Cell 20170601 7

Homeostasis of the gut microbiota critically influences host health and aging. Developing genetically engineered probiotics holds great promise as a new therapeutic paradigm to promote healthy aging. Here, through screening 3,983 Escherichia coli mutants, we discovered that 29 bacterial genes, when deleted, increase longevity in the host Caenorhabditis elegans. A dozen of these bacterial mutants also protect the host from age-related progression of tumor growth and amyloid-beta accumulation. Mec ...[more]

PMID: 28622510

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Project description:The basic reproduction ratio, R0, is a fundamental concept in epidemiology. It is defined as the total number of secondary infections brought on by a single primary infection, in a totally susceptible population. The value of R0 indicates whether a starting epidemic reaches a considerable part of the population and causes a lot of damage, or whether it remains restricted to a relatively small number of individuals. To calculate R0 one has to evaluate an integral that ranges over the duration of the infection of the host. This duration is, of course, limited by remaining host longevity. So, R0 depends on remaining host longevity and in this paper we show that for long-lived hosts this aspect may not be ignored for long-lasting infections. We investigate in particular how this epidemiological measure of pathogen fitness depends on host longevity. For our analyses we adopt and combine a generic within- and between-host model from the literature. To find the optimal strategy for a pathogen from an evolutionary point of view, we focus on the indicator [Formula: see text], i.e., the optimum of R0 as a function of its replication and mutation rates. These are the within-host parameters that the pathogen has at its disposal to optimize its strategy. We show that [Formula: see text] is highly influenced by remaining host longevity in combination with the contact rate between hosts in a susceptible population. In addition, these two parameters determine whether a killer-like or a milker-like strategy is optimal for a given pathogen. In the killer-like strategy the pathogen has a high rate of reproduction within the host in a short time span causing a relatively short disease, whereas in the milker-like strategy the pathogen multiplies relatively slowly, producing a continuous small amount of offspring over time with a small effect on host health. The present research allows for the determination of a bifurcation line in the plane of host longevity versus contact rate that forms the boundary between the milker-like and killer-like regions. This plot shows that for short remaining host longevities the killer-like strategy is optimal, whereas for very long remaining host longevities the milker-like strategy is advantageous. For in-between values of host longevity, the contact rate determines which of both strategies is optimal.

Dataset Information

Microbial Genetic Composition Tunes Host Longevity.

Publications

Microbial Genetic Composition Tunes Host Longevity.

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