Selecting age-related functional characteristics in the human gut microbiome

Conjugation enables the exchange of genetic elements throughout environments, including the human gut microbiome. Conjugative elements can carry and transfer clinically relevant metabolic pathways which makes precise identification of these systems in metagenomic samples clinically important. Here, we outline two distinct methods to identify conjugative systems in the human gut microbiome. We first show that conjugative systems exhibit strong population and age-level stratification. Additionally, we find that the total relative abundance of all conjugative systems present in a sample is not an informative metric to use, regardless of the method of identifying the systems. Finally, we demonstrate that the majority of assembled conjugative systems are not included within metagenomic bins, and that only a small proportion of the binned conjugative systems are included in "high-quality" metagenomic bins. Our findings highlight that conjugative systems differ between general North Americans and a cohort of North American pre-term infants, revealing a potential use as an age-related biomarker. Furthermore, conjugative systems can distinguish between other geographical-based cohorts. Our findings emphasize the need to identify and analyze conjugative systems outside of standard metagenomic binning pipelines.

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Separation of Cohorts on the Basis of Bacterial Type IV Conjugation Systems Identified From Metagenomic Assemblies

10.21203/rs.3.rs-660934/v1 ◽

2021 ◽

Author(s):

Benjamin R Joris ◽

Tyler S Browne ◽

Thomas A Hamilton ◽

David R Edgell ◽

Gregory B Gloor

Keyword(s):

North American ◽

Gut Microbiome ◽

Metagenomic Sequencing ◽

Human Gut ◽

Term Infants ◽

Human Gut Microbiome ◽

Type Iv ◽

Shotgun Metagenomic Sequencing ◽

Age Related ◽

Inflammatory Bowel

Abstract BackgroundConjugation enables the exchange of genetic elements throughout environments, including the human gut microbiome. Conjugative elements can carry and transfer clinically relevant metabolic pathways which makes precise identification of these systems in metagenomic samples clinically important. ResultsHere, we outline two distinct methods to identify conjugative elements in the human gut microbiome. We first show that conjugative elements exhibit strong population and age-level stratification. Furthermore, the taxonomic compositions of the conjugative elements differ from the composition of the metagenome assembled genomes, both in terms of the number of assembled elements and the relative abundances of the assembled systems. Finally, we demonstrate that the majority of assembled conjugative elements are not included within metagenomic bins, and that only a small proportion of the binned conjugative systems are included in "high-quality" metagenomic bins. Our findings highlight that conjugative systems differ between a North American inflammatory bowel disease cohort and a cohort of North American pre-term infants, but in a manner different than metagenome assembled genomes, revealing a potential use as an age-related biomarker. Additionally, conjugative systems can distinguish between other geographical-based cohorts. ConclusionsAnalysis of the human gut microbiome by shotgun metagenomic sequencing has revealed numerous connections to human health outcomes. Our findings emphasize the need to identify and analyze conjugative systems outside of standard metagenomic binning pipelines. We suggest that analysis of type IV conjugative systems should be added to the current metagenomic analysis approaches as they contain much information that could explain differences between cohorts beyond those we investigated.

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Shotgun Metagenomics of Gut Microbiota in Humans with up to Extreme Longevity and the Increasing Role of Xenobiotic Degradation

mSystems ◽

10.1128/msystems.00124-20 ◽

2020 ◽

Vol 5 (2) ◽

Cited By ~ 9

Author(s):

Simone Rampelli ◽

Matteo Soverini ◽

Federica D’Amico ◽

Monica Barone ◽

Teresa Tavella ◽

...

Keyword(s):

Gut Microbiome ◽

Taxonomic Resolution ◽

Human Beings ◽

Human Gut ◽

Shotgun Metagenomics ◽

Human Gut Microbiome ◽

Age Related ◽

General Decline ◽

Extreme Longevity ◽

Xenobiotic Degradation

ABSTRACT The gut microbiome of long-lived people display an increasing abundance of subdominant species, as well as a rearrangement in health-associated bacteria, but less is known about microbiome functions. In order to disentangle the contribution of the gut microbiome to the complex trait of human longevity, we here describe the metagenomic change of the human gut microbiome along with aging in subjects with up to extreme longevity, including centenarians (aged 99 to 104 years) and semisupercentenarians (aged 105 to 109 years), i.e., demographically very uncommon subjects who reach the extreme limit of the human life span. According to our findings, the gut microbiome of centenarians and semisupercentenarians is more suited for xenobiotic degradation and shows a rearrangement in metabolic pathways related to carbohydrate, amino acid, and lipid metabolism. Collectively, our data go beyond the relationship between intestinal bacteria and physiological changes that occur with aging by detailing the shifts in the potential metagenomic functions of the gut microbiome of centenarians and semisupercentenarians as a response to progressive dietary and lifestyle modifications. IMPORTANCE The study of longevity may help us understand how human beings can delay or survive the most frequent age-related diseases and morbidities. In this scenario, the gut microbiome has been proposed as one of the variables to monitor and possibly support healthy aging. Indeed, the disruption of host-gut microbiome homeostasis has been associated with inflammation and intestinal permeability as well as a general decline in bone and cognitive health. Here, we performed a metagenomic assessment of fecal samples from semisupercentenarians, i.e., 105 to 109 years old, in comparison to young adults, the elderly, and centenarians, shedding light on the longest compositional and functional trajectory of the human gut microbiome with aging. In addition to providing a fine taxonomic resolution down to the species level, our study emphasizes the progressive age-related increase in degradation pathways of pervasive xenobiotics in Western societies, possibly as a result of a supportive process within the molecular continuum characterizing aging.

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