A metagenomic catalog of the early-life human gut virome

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Фев. 29, 2024

Early-life human gut microbiome is a pivotal driver of homeostasis and infant health. However, the viral component (known as "virome") remains mostly unexplored. Here, we establish Early-Life Gut Virome (ELGV), catalog 160,478 non-redundant DNA RNA sequences from 8130 virus-like particles (VLPs) enriched or bulk metagenomes in first three years life. By clustering, 82,141 species are identified, 68.3% which absent existing databases built mainly adults, 64 8 based on VLPs-enriched metagenomes, respectively, exhibit potentials biomarkers to distinguish infants adults. With largest longitudinal population profiled by either metagenomic sequencing, track inherent instability temporal development early-life virome, identify differential viruses associated with multiple clinical factors. The mother-infant shared virome interactions between bacteriome early life further expanded. Together, ELGV provides most comprehensive complete blueprint facilitating discovery pediatric disease-virome associations future.

Язык: Английский

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Opportunities and barriers in omics-based biomarker discovery for steatotic liver diseases

Journal of Hepatology, Год журнала: 2024, Номер 81(2), С. 345 - 359

Опубликована: Март 28, 2024

The rising prevalence of liver diseases related to obesity and excessive use alcohol is fuelling an increasing demand for accurate biomarkers aimed at community screening, diagnosis steatohepatitis significant fibrosis, monitoring, prognostication prediction treatment efficacy. Breakthroughs in omics methodologies the power bioinformatics have created excellent opportunity apply technological advances clinical needs, instance development precision personalised medicine. Via technologies, biological processes from genes circulating protein, as well microbiome - including bacteria, viruses fungi, can be investigated on axis. However, there are important barriers omics-based biomarker discovery validation, semi-quantitative measurements untargeted platforms, which may exhibit high analytical, inter- intra-individual variance. Standardising methods need validate them across diverse populations presents a challenge, partly due disease complexity dynamic nature expression different stages. Lack validity causes lost opportunities when studies fail provide knowledge needed regulatory approvals, all contributes delayed translation these discoveries into practice. While no matured implementation, extent data generated has enabled hypothesis-free plethora candidate that warrant further validation. To explore many hepatologists detailed commonalities differences between various layers, both advantages approaches.

Язык: Английский

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Targeting nonalcoholic fatty liver disease via gut microbiome-centered therapies

Gut Microbes, Год журнала: 2023, Номер 15(1)

Опубликована: Июнь 26, 2023

Humans possess abundant amounts of microorganisms, including bacteria, fungi, viruses, and archaea, in their gut. Patients with nonalcoholic fatty liver disease (NAFLD) exhibit alterations gut microbiome an impaired barrier function. Preclinical studies emphasize the significance pathogenesis NAFLD. In this overview, we explore how adjusting could serve as innovative therapeutic strategy for We provide a summary current information on untargeted techniques such probiotics fecal microbiota transplantation, well targeted microbiome-focused therapies engineered prebiotics, postbiotics, phages treatment

Язык: Английский

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Correlation between the gut microbiome and neurodegenerative diseases: a review of metagenomics evidence

Neural Regeneration Research, Год журнала: 2023, Номер 19(4), С. 833 - 845

Опубликована: Авг. 14, 2023

A growing body of evidence suggests that the gut microbiota contributes to development neurodegenerative diseases via microbiota-gut-brain axis. As a contributing factor, dysbiosis always occurs in pathological changes diseases, such as Alzheimer's disease, Parkinson's and amyotrophic lateral sclerosis. High-throughput sequencing technology has helped reveal bidirectional communication between central nervous system enteric is facilitated by microbiota's diverse microorganisms, for both neuroimmune neuroendocrine systems. Here, we summarize bioinformatics analysis wet-biology validation metagenomics with an emphasis on multi-omics studies virome. The pathogen-associated signaling biomarkers identifying brain disorders potential therapeutic targets are also elucidated. Finally, discuss role diet, prebiotics, probiotics, postbiotics exercise interventions remodeling microbiome reducing symptoms diseases.

Язык: Английский

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Alterations in the gut virome are associated with type 2 diabetes and diabetic nephropathy

Gut Microbes, Год журнала: 2023, Номер 15(1)

Опубликована: Июнь 22, 2023

Although changes in gut microbiome have been associated with the development of T2D and its complications, role virome remains largely unknown. Here, we characterized alterations complications diabetic nephropathy (DN) by metagenomic sequencing fecal viral-like particles. Compared controls, subjects, especially those DN, had significantly lower viral richness diversity. 81 species were identified to be altered including a decrease some phages (e.g. Flavobacterium phage Cellulophaga phaga). DN subjects depleted 12 species, Bacteroides phage, Anoxybacillus virus Brevibacillus enriched 2 (Shigella Xylella phage). Multiple functions, particularly lysing host bacteria, markedly reduced DN. Strong viral-bacterial interactions healthy controls disrupted both Moreover, combined use bacterial markers achieved powerful diagnostic performance for AUC 99.03% 98.19%, respectively. Our results suggest that complication are significant diversity, specific loss multiple disruption correlations. The potential

Язык: Английский

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Phage-microbe dynamics after sterile faecal filtrate transplantation in individuals with metabolic syndrome: a double-blind, randomised, placebo-controlled clinical trial assessing efficacy and safety

Nature Communications, Год журнала: 2023, Номер 14(1)

Опубликована: Сен. 12, 2023

Bacteriophages (phages) are bacterial viruses that have been shown to shape microbial communities. Previous studies faecal virome transplantation can decrease weight gain and normalize blood glucose tolerance in diet-induced obese mice. Therefore, we performed a double-blind, randomised, placebo-controlled pilot study which 24 individuals with metabolic syndrome were randomised filtrate (FFT) from lean healthy donor (n = 12) or placebo 12). The primary outcome, change metabolism, secondary outcomes, safety longitudinal changes within the intestinal bacteriome phageome, assessed baseline up 28 days. All included subjects completed analyses. While overall metabolism not significantly different between both groups, FFT is well-tolerated without any serious adverse events. phage virion composition altered two days after as compared placebo, coincides more virulent phage-microbe interactions. In conclusion, provide evidence gut phages be safely administered transiently alter microbiota of recipients.

Язык: Английский

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Integrative metagenomic analysis reveals distinct gut microbial signatures related to obesity

BMC Microbiology, Год журнала: 2024, Номер 24(1)

Опубликована: Апрель 5, 2024

Abstract Obesity is a metabolic disorder closely associated with profound alterations in gut microbial composition. However, the dynamics of species composition and functional changes microbiome obesity remain to be comprehensively investigated. In this study, we conducted meta-analysis metagenomic sequencing data from both obese non-obese individuals across multiple cohorts, totaling 1351 fecal metagenomes. Our results demonstrate significant decrease richness diversity bacteriome virome patients. We identified 38 bacterial including Eubacterium sp. CAG:274, Ruminococcus gnavus , eligens Akkermansia muciniphila, 1 archaeal species, Methanobrevibacter smithii that were significantly altered obesity. Additionally, observed abundance five viral families: Mesyanzhinovviridae Chaseviridae Salasmaviridae Drexlerviridae Casjensviridae . Functional analysis indicated distinct signatures as primary driver for function enrichment obesity, muciniphila bicirculans siraeum drivers healthy control group. our suggest antibiotic resistance genes virulence factors may influence development Finally, demonstrated vOTUs achieved diagnostic accuracy an optimal area under curve 0.766 distinguishing controls. findings offer comprehensive generalizable insights into features potential guide microbiome-based diagnostics.

Язык: Английский

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An immune-competent human gut microphysiological system enables inflammation-modulation by Faecalibacterium prausnitzii

npj Biofilms and Microbiomes, Год журнала: 2024, Номер 10(1)

Опубликована: Март 29, 2024

Abstract Crosstalk of microbes with human gut epithelia and immune cells is crucial for health. However, there no existing system a long-term co-culture innate epithelium oxygen-intolerant commensal microbes, hindering the understanding microbe-immune interactions in controlled manner. Here, we established epithelium-microbe-immune (GuMI) microphysiological to maintain continuous Faecalibacterium prausnitzii/Faecalibacterium duncaniae colonic epithelium, antigen-presenting (APCs, herein dendritic macrophages), CD4 + naive T circulating underneath epithelium. In GuMI-APC condition, multiplex cytokine assays suggested that APCs contribute elevated level cytokines chemokines secreted into both apical basolateral compartments compared GuMI condition lacks APC. F. prausnitzii (GuMI-APC-FP), increased transcription pro-inflammatory genes such as toll-like receptor 1 ( TLR1 ) interferon alpha IFNA1 without significant effect on secretion, bacteria (GuMI-APC-NB). contrast, presence (GuMI-APCT-FP), , IDO1 levels decreased simultaneous increase -induced secretion (e.g., IL8) GuMI-APC-FP cells. These results highlight contribution individual regulating response triggered by . The integration defined populations demonstrated usefulness physiomimetic platform study microbe-epithelial-immune healthy disease conditions.

Язык: Английский

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Gut instincts: Unveiling the connection between gut microbiota and Alzheimer's disease

Clinical Nutrition ESPEN, Год журнала: 2024, Номер 60, С. 266 - 280

Опубликована: Фев. 19, 2024

Язык: Английский

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MetALD: Does it require a different therapeutic option?

Hepatology, Год журнала: 2024, Номер 80(6), С. 1424 - 1440

Опубликована: Май 31, 2024

New guidelines for the definitions of steatotic liver disease have named entity metabolic dysfunction and alcohol-associated (MetALD) as an overlap condition dysfunction–associated (MASLD) disease. There is a broad range therapeutics in all stages development MASLD, but these therapeutics, general, not been studied patients with significant ongoing alcohol use. In this review, we discuss current understanding endogenous exogenous risks MASLD MetALD. Rational strategies therapeutic intervention MetALD include biopsychosocial interventions, use cessation strategies, including medications disorder, judicious Therapeutics promise incretin-based therapies, FGF21 agonists, thyroid hormone receptor beta sodium-glucose co-transporter 2 inhibitors, agents to modify de novo lipogenesis. Currently, glucagon-like peptide 1 agonists peroxisome proliferator–activated γ largest body literature supporting their there paucity trials From existing studies, it clear if unique or combinatorial approach are needed Further elucidation safety benefits MASLD-related therapies paramount importance advancing carefully designed inclusive clinical trials.

Язык: Английский

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