skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Microbiome-wide association studies link dynamic microbial consortia to disease

Abstract

Rapid advances in DNA sequencing, metabolomics, proteomics and computational tools are dramatically increasing access to the microbiome and identification of its links with disease. In particular, time-series studies and multiple molecular perspectives are facilitating microbiome-wide association studies, which are analogous to genome-wide association studies. Early findings point to actionable outcomes of microbiome-wide association studies, although their clinical application has yet to be approved. An appreciation of the complexity of interactions among the microbiome and the host's diet, chemistry and health, as well as determining the frequency of observations that are needed to capture and integrate this dynamic interface, is paramount for developing precision diagnostics and therapies that are based on the microbiome.

Authors:
; ; ; ; ; ; ; ;
Publication Date:
Research Org.:
Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1353345
Report Number(s):
PNNL-SA-116462
Journal ID: ISSN 0028-0836
DOE Contract Number:
AC05-76RL01830
Resource Type:
Journal Article
Resource Relation:
Journal Name: Nature (London); Journal Volume: 535; Journal Issue: 7610
Country of Publication:
United States
Language:
English

Citation Formats

Gilbert, Jack A., Quinn, Robert A., Debelius, Justine, Xu, Zhenjiang Z., Morton, James, Garg, Neha, Jansson, Janet K., Dorrestein, Pieter C., and Knight, Rob. Microbiome-wide association studies link dynamic microbial consortia to disease. United States: N. p., 2016. Web. doi:10.1038/nature18850.
Gilbert, Jack A., Quinn, Robert A., Debelius, Justine, Xu, Zhenjiang Z., Morton, James, Garg, Neha, Jansson, Janet K., Dorrestein, Pieter C., & Knight, Rob. Microbiome-wide association studies link dynamic microbial consortia to disease. United States. doi:10.1038/nature18850.
Gilbert, Jack A., Quinn, Robert A., Debelius, Justine, Xu, Zhenjiang Z., Morton, James, Garg, Neha, Jansson, Janet K., Dorrestein, Pieter C., and Knight, Rob. Wed . "Microbiome-wide association studies link dynamic microbial consortia to disease". United States. doi:10.1038/nature18850.
@article{osti_1353345,
title = {Microbiome-wide association studies link dynamic microbial consortia to disease},
author = {Gilbert, Jack A. and Quinn, Robert A. and Debelius, Justine and Xu, Zhenjiang Z. and Morton, James and Garg, Neha and Jansson, Janet K. and Dorrestein, Pieter C. and Knight, Rob},
abstractNote = {Rapid advances in DNA sequencing, metabolomics, proteomics and computational tools are dramatically increasing access to the microbiome and identification of its links with disease. In particular, time-series studies and multiple molecular perspectives are facilitating microbiome-wide association studies, which are analogous to genome-wide association studies. Early findings point to actionable outcomes of microbiome-wide association studies, although their clinical application has yet to be approved. An appreciation of the complexity of interactions among the microbiome and the host's diet, chemistry and health, as well as determining the frequency of observations that are needed to capture and integrate this dynamic interface, is paramount for developing precision diagnostics and therapies that are based on the microbiome.},
doi = {10.1038/nature18850},
journal = {Nature (London)},
number = 7610,
volume = 535,
place = {United States},
year = {Wed Jul 06 00:00:00 EDT 2016},
month = {Wed Jul 06 00:00:00 EDT 2016}
}
  • Rapid advances in DNA sequencing, metabolomics, proteomics and computation dramatically increase accessibility of microbiome studies and identify links between the microbiome and disease. Microbial time-series and multiple molecular perspectives enable Microbiome-Wide Association Studies (MWAS), analogous to Genome-Wide Association Studies (GWAS). Rapid research advances point towards actionable results, although approved clinical tests based on MWAS are still in the future. Appreciating the complexity of interactions between diet, chemistry, health and the microbiome, and determining the frequency of observations needed to capture and integrate this dynamic interface, is paramount for addressing the need for personalized and precision microbiome-based diagnostics and therapies.
  • Phenome-wide association is a novel reverse genetic strategy to analyze genome-to-phenome relations in human clinical cohorts. Here we test this approach using a large murine population segregating for ~5 million sequence variants, and we compare our results to those extracted from a matched analysis of gene variants in a large human cohort. For the mouse cohort, we amassed a deep and broad open-access phenome consisting of ~4,500 metabolic, physiological, pharmacological and behavioural traits, and more than 90 independent expression quantitative trait locus (QTL), transcriptome, proteome, metagenome and metabolome data sets-by far the largest coherent phenome for any experimental cohort (www.genenetwork.org).more » Here, we tested downstream effects of subsets of variants and discovered several novel associations, including a missense mutation in fumarate hydratase that controls variation in the mitochondrial unfolded protein response in both mouse and Caenorhabditis elegans, and missense mutations in Col6a5 that underlies variation in bone mineral density in both mouse and human.« less
  • Microbial souring (H[sub 2]S production) in porous media was investigated in an anaerobic upflow porous media reactor at 60 C using microbial consortia obtained from oil reservoirs. Multiple carbon sources (formate, acetate, propionate, iso and n-butyrates) found in reservoir waters as well as sulfate as the electron acceptor were used. Kinetics and rates of souring in the reactor system were analyzed. Higher volumetric substrate consumption rates (organic acids and sulfate) and a higher volumetric H[sub 2]S production rate were found at the front part of the reactor column after H[sub 2]S production had stabilized. Concentration gradients for the substrates (organicmore » acids and sulfate) and H[sub 2]S were generated along the column. Biomass accumulation throughout the entire column was observed. The average specific sulfate reduction rate (H[sub 2]S production rate) in the present reactor after H[sub 2]S production had stabilized was calculated to be 11.62 [+-] 2.22 mg sulfate-S/day g biomass.« less
  • With recent rapid advances in mapping of the human genome, including highly polymorphic and closely linked markers, studies of marker associations with disease are increasingly relevant for mapping disease genes. The use of nuclear-family data in association studies was initially developed to avoid possible ethnic mismatching between patients and randomly ascertained controls. The parental marker alleles not transmitted to an affected child or never transmitted to an affected sib pair form the so-called AFBAC (affected family-based controls) population. In this paper, the theroetical foundation of the AFBAC method is proved for any single-locus model of disease and for any nuclearmore » family-based ascertainment scheme. In a random-mating population, when there is a marker association with disease, the AFBAC population provides an unbiased estimate of the overall population (control) marker alleles when the recombination fraction {theta} between the marker and disease genes is sufficiently small that it can be taken as zero ({theta}=0). With population stratification, only marker associations present in the subpopulations will be detected with family-based analyses. Of more importance, however, is the fact that, when {theta}=0, differences between transmitted parental (patient) marker allele frequencies and non-or never-transmitted parental marker allele frequencies (implying a marker association with disease) can only be observed for marker genes linked to a disease gene ({theta}<{1/2}). Thus, associations of unlinked marker loci with disease at the population level, caused by population stratification, migration, or admixture, are eliminated. This validates the use of family-based association tests as an appropriate strategy for mapping disease genes. 52 refs., 1 fig.« less