The long-term genetic stability and individual specificity of the human gut microbiome

Chen, Lianmin; Wang, Daoming; Garmaeva, Sanzhima; Kurilshikov, Alexander; Vila, Arnau Vich; Gaćeša, Ranko; Sinha, Trishla; Segal, Eran; Weersma, Rinse K.; Wijmenga, Cisca; Zhernakova, Alexandra; Fu, Jingyuan

doi:10.1016/j.cell.2021.03.024

Cited by 230 publications

(199 citation statements)

References 67 publications

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“…To study the temporal stability of the crAss-like phages, we used the data from the LLD (Zhernakova et al , 2016) and LLD follow-up (Chen et al , 2021) cohorts: samples collected from the same 338 individuals at two timepoints approximately 4-years apart. First, we assessed the stability of individual genus-level clusters of crAss-like phages.…”

Section: Resultsmentioning

confidence: 99%

“…Analysis of samples from 388 individuals taken at two timepoints (Chen et al , 2021; Zhernakova et al , 2016) allowed us to explore the temporal stability of crAss-like phages. Despite the 4-year period separating the two timepoints, we observed a degree of stability both at the level of individual genus-level clusters (on average, 41% of individuals positive for a frequently detected genus-level cluster were positive at both timepoints) and at the level of the overall composition of the crAss-like fraction of the virome (on average, dissimilarity between samples collected from the same individual at the two timepoints was lower than the dissimilarity between pairs of samples collected from different individuals at the same timepoint).…”

Section: Discussionmentioning

confidence: 99%

“…Data used in the project included gut metagenome sequencing data and human phenotype data for 1135 LLD cohort participants (Tigchelaar et al , 2015; Zhernakova et al , 2016), 338 LLD follow-up cohort participants (Chen et al , 2021) and 298 participants of the 300OB cohort (Ter Horst et al , 2020). A total of 520 gut metagenome samples from the IBD cohort (Imhann et al , 2019) containing ≥10 million sequencing reads were screened for the presence of crAss-like phages.…”

Section: Methodsmentioning

confidence: 99%

“…To further our understanding of the diversity, abundance and functional role of the crAss-like phages in the human gut microbial community, we identified and analyzed crAss-like phages present in 2291 metagenomic samples from four cohorts collected in the Netherlands. These include 1135 baseline and 338 follow-up samples from the population cohorts Lifelines-DEEP (LLD) and LLD follow-up (Chen et al, 2021; Tigchelaar et al, 2015; Zhernakova et al, 2016), 298 samples from the 300-Obesity cohort (300OB) (Ter Horst et al, 2020), and 520 samples from a cohort of patients with IBD (Imhann et al, 2019; Vich Vila et al, 2018). Analysis of these samples led to the discovery of crAss-like phage genomes prototyping 125 novel species.…”

Section: Introductionmentioning

confidence: 99%

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Discovery, diversity and functional associations of crAss-like phages in human gut metagenomes from four Dutch cohorts

Gulyaeva

Garmaeva

et al. 2021

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The crAss-like phages are a diverse group of related viruses that includes one of the most abundant viruses of the human gut. To explore their diversity and functional role in human population and clinical cohorts, we analyzed gut metagenomic data collected from more than 2000 individuals from the Netherlands. We discovered 125 novel species-level and 32 novel genus-level clusters of crAss-like phages, all belonging to five previously recognized groups associated with the human gut. Analysis of their genomic features revealed that closely related crAss-like phages can possess strikingly divergent regions responsible for transcription, presumably acquired through recombination. Prediction of crAss-like phage hosts pointed primarily to bacteria of the phylum Bacteroidetes, consistent with previous reports. Finally, we explored the temporal stability of crAss-like phages over a 4-year period and identified associations between the abundance of crAss-like phages and several human phenotypes, including depletion of crAss-like phages in inflammatory bowel disease patients.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Discovery, diversity and functional associations of crAss-like phages in human gut metagenomes from four Dutch cohorts

Gulyaeva

Garmaeva

et al. 2021

Preprint

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“…As diet, genetics and gut microbiome are highly heterogeneous between different countries, we aimed to identify dietary, genetic and microbial determinants of plasma metabolites in the Dutch population and to characterize the main drivers of inter-individual metabolic variability. To do so, we quanti ed the plasma levels of 1,183 metabolites in 1,368 individuals from the population-based Lifelines-Deep (LLD) 5 and Genome of the Netherlands (GoNL) 6 cohorts, including 311 LLD individuals who were followed-up after 4 years 7 (Figure S1A). For each participant, we had information on the gut microbiome, genetic background and dietary habits (Figure S1A).…”

Section: Introductionmentioning

confidence: 99%

Dominant drivers of the human plasma metabolome

Chen

Andreu‐Sánchez

et al. 2021

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The human plasma metabolome contains thousands of metabolites that are dependent on an individual’s diet, genetics and gut microbiome, and on their interactions. By assessing 1,183 plasma metabolites in 1,368 extensively phenotyped individuals from the LifeLines-DEEP and GoNL cohorts, we quantified the proportion of inter-individual variation of the plasma metabolome explained by different factors and characterized 605 metabolites that are dominantly driven by diet, 85 driven by the gut microbiome, and 56 driven by genetics. We also developed a model that reflects the quality of an individual’s diet using 76 mostly diet-driven metabolites. By applying Mendelian randomization (MR) and mediation analyses, we reveal putative causal relationships between diet, gut microbiome and metabolites. For example, MR supports the causal effect of Eubacterium rectale in decreasing plasma levels of toxic p-cresol and p-cresol sulfate, two metabolites related to cardiometabolic risk and chronic kidney disease. We further followed-up the plasma metabolome profile in 311 individuals after 4 years and observe that the metabolites with more variance explained by genetics, microbiome or diet are also more temporarily stable. Altogether, our characterization of the dominant drivers of plasma metabolites can help in the design of therapeutic approaches that target the diet, human genome, or gut microbiome to drive a healthy metabolome.

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Toward a Deeper Understanding of Gut Microbiome in Depression: The Promise of Clinical Applicability

et al. 2022

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The emergence of the coronavirus disease 2019 pandemic has dramatically increased the global prevalence of depression. Unfortunately, antidepressant drugs benefit only a small minority of patients. Thus, there is an urgent need to develop new interventions. Accumulating evidence supports a causal relationship between gut microbiota dysbiosis and depression. To advance microbiota‐based diagnostics and therapeutics of depression, a comprehensive overview of microbial alterations in depression is presented to identify effector microbial biomarkers. This procedure generated 215 bacterial taxa from humans and 312 from animal models. Compared to controls, depression shows significant differences in β‐diversity, but no changes in microbial richness and diversity. Additionally, species‐specific microbial changes are identified like increased Eggerthella in humans and decreased Acetatifactor in rodent models. Moreover, a disrupted microbiome balance and functional changes, characterized by an enrichment of pro‐inflammatory bacteria (e.g., Desulfovibrio and Escherichia/Shigella) and depletion of anti‐inflammatory butyrate‐producing bacteria (e.g., Bifidobacterium and Faecalibacterium) are consistently shared across species. Confounding effects of geographical region, depression type, and intestinal segments are also investigated. Ultimately, a total of 178 species and subspecies probiotics are identified to alleviate the depressive phenotypes. Current findings provide a foundation for developing microbiota‐based diagnostics and therapeutics and advancing microbiota‐oriented precision medicine for depression.

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The long-term genetic stability and individual specificity of the human gut microbiome

Cited by 230 publications

References 67 publications

Discovery, diversity and functional associations of crAss-like phages in human gut metagenomes from four Dutch cohorts

Discovery, diversity and functional associations of crAss-like phages in human gut metagenomes from four Dutch cohorts

Dominant drivers of the human plasma metabolome

Toward a Deeper Understanding of Gut Microbiome in Depression: The Promise of Clinical Applicability

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