Metagenomic and metabolomic remodeling in nonagenarians and centenarians and its association with genetic and socioeconomic factors

Xu, Qian; Wu, Chunyan; Zhu, Qi; Gao, Renyuan; Lu, Jianquan; Valles‐Colomer, Mireia; Zhu, Jian; Yin, Fang; Huang, Lei; Ding, Lei; Zhang, Xiaohui; Zhang, Yonghui; Xiong, Xiao; Bi, Miaomiao; Chen, Xiang; Zhu, Yefei; Liu, Lin; Liu, Yongqiang; Chen, Yongshen; Fan, Jian Gao; Sun, Yan; Wang, Jun; Cao, Zhan; Fan, Chunsun; Ehrlich, S. Dusko; Segata, Nicola; Qin, Nan; Qin, Huanlong

doi:10.1038/s43587-022-00193-0

Cited by 28 publications

(22 citation statements)

References 57 publications

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“…Choline availability has also been linked to retinal degeneration [52][53][54] . Further confirming our results, the connection between FLVCR1 and choline was recently described as a metabolite quantitative trait loci association in nonagenarians and centenarians 55 . Our findings therefore suggest that patients with mutations in FLVCR1 may benefit from choline supplementation, a well-tolerated dietary intervention 56 .…”

Section: Discussionsupporting

confidence: 92%

Integrative genetic analysis identifies FLVCR1 as an essential component of choline transport in mammals

Kenny

Khan

Son

et al. 2022

Preprint

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Genome-wide association studies (GWAS) of serum metabolites have the potential to uncover genes that influence human metabolism. Here, we combined an integrative genetic analysis associating serum metabolites to membrane transporters with a coessentiality map of metabolic genes. This analysis revealed a connection between feline leukemia virus subgroup C cellular receptor 1 (FLVCR1) - a plasma membrane protein - and phosphocholine, a downstream metabolite of choline metabolism. Loss of FLVCR1 in human cells and in mice strongly impairs choline metabolism due to a block in choline import. Consistently, CRISPR-based genetic screens identified several components of the membrane phospholipid machinery as synthetic lethal with FLVCR1 loss. Finally, cells lacking FLVCR1 exhibit mitochondrial defects and upregulate the integrated stress response (ISR) through heme regulated inhibitors kinase (HRI). Altogether, these findings identify FLVCR1 as a universal mediator of choline transport in mammals and provide a platform to discover substrates for unknown metabolite transporters.

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Section: Discussionsupporting

confidence: 92%

Integrative genetic analysis identifies FLVCR1 as an essential component of choline transport in mammals

Kenny

Khan

Son

et al. 2022

Preprint

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“…China_1 dataset. A total of 116 nonagenarians and centenarians (97 female, 19 male, 94-105 years old) and 231 of their offspring (79 female, 152 male, 50-85 years old) in the city of Qidong ( Jiangsu province, China) were enroled (considered here as a westernized population) 63 . All participants were free of major illnesses at the time of inclusion.…”

Section: Metagenomic Datasetsmentioning

confidence: 99%

The person-to-person transmission landscape of the gut and oral microbiomes

Valles‐Colomer

Blanco-Míguez

Manghi

et al. 2023

Nature

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182

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The human microbiome is an integral component of the human body and a co-determinant of several health conditions1,2. However, the extent to which interpersonal relations shape the individual genetic makeup of the microbiome and its transmission within and across populations remains largely unknown3,4. Here, capitalizing on more than 9,700 human metagenomes and computational strain-level profiling, we detected extensive bacterial strain sharing across individuals (more than 10 million instances) with distinct mother-to-infant, intra-household and intra-population transmission patterns. Mother-to-infant gut microbiome transmission was considerable and stable during infancy (around 50% of the same strains among shared species (strain-sharing rate)) and remained detectable at older ages. By contrast, the transmission of the oral microbiome occurred largely horizontally and was enhanced by the duration of cohabitation. There was substantial strain sharing among cohabiting individuals, with 12% and 32% median strain-sharing rates for the gut and oral microbiomes, and time since cohabitation affected strain sharing more than age or genetics did. Bacterial strain sharing additionally recapitulated host population structures better than species-level profiles did. Finally, distinct taxa appeared as efficient spreaders across transmission modes and were associated with different predicted bacterial phenotypes linked with out-of-host survival capabilities. The extent of microorganism transmission that we describe underscores its relevance in human microbiome studies5, especially those on non-infectious, microbiome-associated diseases.

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“…Since its original publication in 2020, GMWI has been used in studies focused on the effects of environmental ( Gacesa et al , 2022 ) and genetic/socioeconomic ( Xu et al , 2022 ) factors on the human gut microbiome. In these studies, GMWI was used to compare groups of interest, such as different age cohorts, case/controls and medication users/non-users.…”

Section: Introductionmentioning

confidence: 99%

“…In these studies, GMWI was used to compare groups of interest, such as different age cohorts, case/controls and medication users/non-users. Moreover, our health-prevalent/-scarce species were used to confirm the health relevance of a newly computed ‘Longevous Gut Microbiota Signature’ species set found by Xu et al (2022) . As an interesting extension of our tool for household pets, the GMWI strategy was applied to assess the gut health of cats ( Sung et al , 2022 ).…”

Section: Introductionmentioning

confidence: 99%

GMWI-webtool: a user-friendly browser application for assessing health through metagenomic gut microbiome profiling

et al. 2023

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Summary We recently introduced the Gut Microbiome Wellness Index, a stool metagenome-based indicator for assessing health by determining the likelihood of disease given the state of one’s gut microbiome. The calculation of our wellness index depends on the relative abundances of health-prevalent and health-scarce species. Encouragingly, GMWI has already been utilized in various studies focusing on differences in the gut microbiome between cases and controls. Herein, we introduce the GMWI-webtool, a user-friendly browser application that computes GMWI, health-prevalent/-scarce species’ relative abundances, and α-diversities from stool shotgun metagenome taxonomic profiles. Users of our interactive online tool can visualize their results and compare them side-by-side with those from our pooled reference dataset of metagenomes, as well as export data in.csv format and high-resolution figures. Availability and implementation GMWI-webtool is freely available here: https://gmwi-webtool.github.io/. Source code: https://github.com/danielchang2002/GMWI-webtool. Supplementary information Supplementary data are available at Bioinformatics online.

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Metagenomic and metabolomic remodeling in nonagenarians and centenarians and its association with genetic and socioeconomic factors

Cited by 28 publications

References 57 publications

Integrative genetic analysis identifies FLVCR1 as an essential component of choline transport in mammals

Integrative genetic analysis identifies FLVCR1 as an essential component of choline transport in mammals

The person-to-person transmission landscape of the gut and oral microbiomes

GMWI-webtool: a user-friendly browser application for assessing health through metagenomic gut microbiome profiling

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