Pan-cancer analyses reveal cancer-type-specific fungal ecologies and bacteriome interactions

Cell, Journal Year: 2022, Volume and Issue: 185(20), P. 3789 - 3806.e17

Published: Sept. 1, 2022

Cancer-microbe associations have been explored for centuries, but cancer-associated fungi rarely examined. Here, we comprehensively characterize the cancer mycobiome within 17,401 patient tissue, blood, and plasma samples across 35 types in four independent cohorts. We report fungal DNA cells at low abundances many major human cancers, with differences community compositions that differ among types, even when accounting technical background. Fungal histological staining of tissue microarrays supported intratumoral presence frequent spatial association macrophages. Comparing communities matched bacteriomes immunomes revealed co-occurring bi-domain ecologies, often permissive, rather than competitive, microenvironments distinct immune responses. Clinically focused assessments suggested prognostic diagnostic capacities mycobiomes, stage I synergistic predictive performance bacteriomes.

Language: Английский

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Greengenes2 unifies microbial data in a single reference tree

Nature Biotechnology, Journal Year: 2023, Volume and Issue: 42(5), P. 715 - 718

Published: July 27, 2023

Abstract Studies using 16S rRNA and shotgun metagenomics typically yield different results, usually attributed to PCR amplification biases. We introduce Greengenes2, a reference tree that unifies genomic databases in consistent, integrated resource. By inserting sequences into whole-genome phylogeny, we show metagenomic data generated from the same samples agree principal coordinates space, taxonomy phenotype effect size when analyzed with tree.

Language: Английский

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Standardized multi-omics of Earth’s microbiomes reveals microbial and metabolite diversity

Nature Microbiology, Journal Year: 2022, Volume and Issue: 7(12), P. 2128 - 2150

Published: Nov. 28, 2022

Despite advances in sequencing, lack of standardization makes comparisons across studies challenging and hampers insights into the structure function microbial communities multiple habitats on a planetary scale. Here we present multi-omics analysis diverse set 880 community samples collected for Earth Microbiome Project. We include amplicon (16S, 18S, ITS) shotgun metagenomic sequence data, untargeted metabolomics data (liquid chromatography-tandem mass spectrometry gas chromatography spectrometry). used standardized protocols analytical methods to characterize communities, focusing relationships co-occurrences microbially related metabolites taxa environments, thus allowing us explore diversity at extraordinary In addition reference database metabolomic provide framework incorporating additional studies, enabling expansion existing knowledge form an evolving resource. demonstrate utility this by testing hypothesis that every microbe metabolite is everywhere but environment selects. Our results show exhibits turnover nestedness both environment, whereas relative abundances vary co-occur with specific consortia habitat-specific manner. additionally power certain chemistry, particular terpenoids, distinguishing Earth's environments (for example, terrestrial plant surfaces soils, freshwater marine animal stool), as well microbes including Conexibacter woesei (terrestrial soils), Haloquadratum walsbyi (marine deposits) Pantoea dispersa detritus). This Resource provides insight within from Earth, informing chemical ecology, foundation microbiome hosts environment.

Language: Английский

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Multi-level analysis of the gut–brain axis shows autism spectrum disorder-associated molecular and microbial profiles

Nature Neuroscience, Journal Year: 2023, Volume and Issue: 26(7), P. 1208 - 1217

Published: June 26, 2023

Autism spectrum disorder (ASD) is a neurodevelopmental characterized by heterogeneous cognitive, behavioral and communication impairments. Disruption of the gut-brain axis (GBA) has been implicated in ASD although with limited reproducibility across studies. In this study, we developed Bayesian differential ranking algorithm to identify ASD-associated molecular taxa profiles 10 cross-sectional microbiome datasets 15 other datasets, including dietary patterns, metabolomics, cytokine human brain gene expression profiles. We found functional architecture along GBA that correlates heterogeneity phenotypes, it amino acid, carbohydrate lipid predominantly encoded microbial species genera Prevotella, Bifidobacterium, Desulfovibrio Bacteroides changes, restrictive patterns pro-inflammatory The revealed age-matched sex-matched cohorts not present sibling-matched cohorts. also show strong association between temporal changes composition phenotypes. summary, propose framework leverage multi-omic from well-defined investigate how influences ASD.

Language: Английский

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Robustness of cancer microbiome signals over a broad range of methodological variation

Oncogene, Journal Year: 2024, Volume and Issue: 43(15), P. 1127 - 1148

Published: Feb. 23, 2024

Abstract In 2020, we identified cancer-specific microbial signals in The Cancer Genome Atlas (TCGA) [1]. Multiple peer-reviewed papers independently verified or extended our findings [2–12]. Given this impact, carefully considered concerns by Gihawi et al. [13] that batch correction and database contamination with host sequences artificially created the appearance of cancer type-specific microbiomes. (1) We tested comparing raw Voom-SNM-corrected data per-batch, finding predictive equivalence significantly similar features. found consistent results a modern microbiome-specific method (ConQuR [14]), when restricting to taxa an independent, highly-decontaminated cohort. (2) Using Conterminator [15], low levels human original databases (~1% genomes). demonstrated increased detection reads was due using newer genome reference. (3) developed Exhaustive, twice as sensitive Conterminator, clean RefSeq. comprehensively host-deplete TCGA many (pan)genome references. repeated all analyses pipeline, These extensive re-analyses updated methods validate conclusion signatures exist TCGA, show they are robust methodology.

Language: Английский

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Dermal injury drives a skin to gut axis that disrupts the intestinal microbiome and intestinal immune homeostasis in mice

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: April 8, 2024

Abstract The composition of the microbial community in intestine may influence functions distant organs such as brain, lung, and skin. These microbes can promote disease or have beneficial functions, leading to hypothesis that gut explain co-occurrence intestinal skin diseases. Here, we show reverse occur, directly alters microbiome. Disruption dermis by wounding digestion dermal hyaluronan results increased expression colon host defense genes Reg3 Muc2 , changes behavior bacteria. Enhanced is induced vitro exposure released these interventions. change microbiome after functionally important bacteria penetrate epithelium enhance colitis from dextran sodium sulfate (DSS) seen ability rescue associated DSS with oral antibiotics, germ-free mice, fecal transplantation unwounded mice wounds. observations provide direct evidence a skin-gut axis demonstrating damage disrupts homeostasis

Language: Английский

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Medication use is associated with distinct microbial features in anxiety and depression

Molecular Psychiatry, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 10, 2025

Abstract This study investigated the relationship between gut microbiota and neuropsychiatric disorders (NPDs), specifically anxiety disorder (ANXD) and/or major depressive (MDD), as defined by Diagnostic Statistical Manual of Mental Disorders (DSM)-IV or V criteria. The also examined influence medication use, particularly antidepressants anxiolytics, classified through Anatomical Therapeutic Chemical (ATC) Classification System, on microbiota. Both 16S rRNA gene amplicon sequencing (16S) shallow shotgun (WGS) were performed DNA extracted from 666 fecal samples Tulsa-1000 Neurocomputational Mechanisms Affiliation Personality Study Center for Biomedical Research Excellence (NeuroMAP CoBRE) cohorts. results highlight significant use; antidepressant use is associated with differences in beta diversity has a larger effect size than NPD diagnosis. Next, specific microbes ANXD MDD, highlighting their potential non-pharmacological intervention. Finally, demonstrated capability Random Forest classifiers to predict diagnoses microbial profiles, suggesting promising direction biomarkers NPD. Though sizes females males, similar trends emerged both sexes. These findings encourage future research microbiota’s role its interactions pharmacological treatments.

Language: Английский

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A Comparison of Six DNA Extraction Protocols for 16S, ITS and Shotgun Metagenomic Sequencing of Microbial Communities

BioTechniques, Journal Year: 2022, Volume and Issue: 73(1), P. 34 - 46

Published: June 17, 2022

Microbial communities contain a broad phylogenetic diversity of organisms; however, the majority methods center on describing bacteria and archaea. Fungi are important symbionts in many ecosystems potentially members human microbiome, beyond those that can cause disease. To expand our analysis microbial to include data from fungal internal transcribed spacer (ITS) region, five candidate DNA extraction kits were compared against standardized protocol for archaea using 16S rRNA gene amplicon- shotgun metagenomics sequencing. The results presented considering diverse panel host-associated environmental sample types comparing cost, processing time, well-to-well contamination, yield, limit detection community composition among protocols. Across all criteria, MagMAX Microbiome kit was found perform best. PowerSoil Pro performed comparably but with increased cost per overall time. Zymo MagBead, NucleoMag Food Norgen Stool included.

Language: Английский

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Paired microbiome and metabolome analyses associate bile acid changes with colorectal cancer progression

Cell Reports, Journal Year: 2023, Volume and Issue: 42(8), P. 112997 - 112997

Published: Aug. 1, 2023

Colorectal cancer (CRC) is driven by genomic alterations in concert with dietary influences, the gut microbiome implicated as an effector disease development and progression. While meta-analyses have provided mechanistic insight into patients CRC, study heterogeneity has limited causal associations. Using multi-omics studies on genetically controlled cohorts of mice, we identify diet major driver microbial metabolomic differences, reductions α diversity widespread changes cecal metabolites seen high-fat (HFD)-fed mice. In addition, non-classic amino acid conjugation bile cholic (AA-CA) increased HFD. We show that AA-CAs impact intestinal stem cell growth demonstrate Ileibacterium valens Ruminococcus gnavus are able to synthesize these AA-CAs. This dataset implicates diet-induced shifts metabolome progression potential utility future diagnostic therapeutic developments.

Language: Английский

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Comprehensive evaluation of shotgun metagenomics, amplicon sequencing, and harmonization of these platforms for epidemiological studies

Cell Reports Methods, Journal Year: 2023, Volume and Issue: 3(1), P. 100391 - 100391

Published: Jan. 1, 2023

In a large cohort of 1,772 participants from the Hispanic Community Health Study/Study Latinos with overlapping 16SV4 rRNA gene (bacterial amplicon), ITS1 (fungal and shotgun sequencing data, we demonstrate that amplicon metagenomics offer same level taxonomic accuracy for bacteria at genus even shallow depths. contrast, fungal taxa, did not observe meaningful agreements between results. Finally, show data can be harmonized pooled to yield larger microbiome datasets excellent agreement (<1% effect size variance across three independent outcomes) using amplicon/shotgun compared pure metagenomic analysis. Thus, there are multiple approaches study in epidemiological studies, provide demonstration powerful pooling approach will allow researchers leverage massive amount generated over last two decades.

Language: Английский

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