Metabolomics

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Joe Ham
Posts: 489
Joined: Fri 27 Jul 2007 6:15
Location: New Mexico, USA

Metabolomics

Post by Joe Ham » Tue 1 Jul 2008 5:32

Signs of a long life

Jun 26th 2008

From The Economist print edition
Rummaging through the by-products of cells and looking for patterns could help to unlock the secrets of better health
Illustration by Russell Cobb

PERSONALISED medicine offers a huge promise. It would, in theory, be possible to identify what diseases someone risks getting as they age, predict how those diseases will progress and show how they will respond to therapy—all before any symptoms are present. And by doing this early, it could mean that those diseases are easier to treat. It is the sort of medical crystal-ball gazing that was supposed to be one of the benefits of the Human Genome Project, although it is still a long way from yielding the benefits promised on its behalf. However, there is another “-ome” that contains a vast amount of information about a person’s health and now its secrets are starting to be unravelled too.

Metabolomics studies metabolites, the by-products of the hundreds of thousands of chemical reactions that continuously go on in every cell of the human body. Because blood and urine are packed with these compounds, it should be possible to detect and analyse them. If, say, a tumour was growing somewhere then, long before any existing methods can detect it, the combination of metabolites from the dividing cancer cells will produce a new pattern, different from that seen in healthy tissue. Such metabolic changes could be picked up by computer programs, adapted from those credit-card companies use to detect crime by spotting sudden and unusual spending patterns amid millions of ordinary transactions.

How far away is this vision? It is beginning. Douglas Kell, a researcher at the University of Manchester in Britain, has already created a computer model based on metabolite profiles in blood plasma that can single out pregnant women who are developing pre-eclampsia, or dangerously high blood pressure. Research published last year by Rima Kaddurah-Daouk, a psychiatrist at the Duke University Medical Centre in America, may not only provide a test for schizophrenia, but also help with its treatment. She found a pattern of metabolites present only in the blood of people who had been diagnosed with schizophrenia. The patterns change according to the antipsychotic drugs patients take and this may throw light on why some respond well to certain drugs, but others suffer severe side-effects.

Studying genes alone does not provide such detail. Genes are similar to the plans for a house; they show what it looks like, but not what people are getting up to inside. One way of getting a snapshot of their lives would be to rummage through their rubbish, and that is pretty much what metabolomics does.

“If I asked someone to hold their breath for a while and we were monitoring their genome, we would think nothing had happened,” says David Wishart, head of the Human Metabolome Project at the University of Alberta in Canada. “But if we took a look at their metabolome, we would see all kinds of wild changes.” Dr Wishart and his team of 50 scientists late last year released the first draft of the human metabolome—a database that contains the chemical fingerprints of some 3,000 metabolites, 1,200 drugs and 3,500 food components found in the human body.

One use for such information could be to help people with their diet. Advice about healthy living tends to consist of generalisations, like “eat low-fat products”. But there are big differences in the way people respond to food. About a third of people have problems with a very low-fat diet, says Lori Hoolihan of the Dairy Council of California. “It produces metabolic reactions that actually cause harmful LDL cholesterol to rise, increasing the risk of heart disease,” she says. Metabolic markers might pick up such variations.
-ome cooking

Yet personal diets bring another set of problems. As people’s responses to different foods become better understood, meals could become more like a course of medical treatment than a pleasure. And difficulties emerge. “How do you feed a family when everyone is on an individual diet?” asks Dr Hoolihan. “What happens to the family dinner?”

Despite such reservations, efforts towards healthier living are set to get more complicated. This is because there is another, even more elaborate and interconnected -ome. That is the microbiome and it covers the trillions of bacteria that treat people as their home. There are, for instance, in the crook of your elbow as many as six different types of bacteria, processing the fats that ooze from your skin and helping to moisturise it in return. At least 1,000 other species colonise the mouth, nose and gut. Two big projects have just begun to catalogue them all and understand what they do (see article).

The work is already starting to produce some surprises. Jeremy Nicholson of Imperial College London is exploring both the microbiome and the metabolome. His work suggests that looking for genetic links to chronic diseases like obesity, hypertension and heart disease may even be a waste of time.

Chinese and Japanese people are very similar at a genetic level, but Dr Nicholson found big differences in the type and variety of metabolites in their blood and urine. “It is a clear illustration of the major role played by diet and culture on your risk of chronic disorders,” he says. “Metabolomics can provide very specific pointers as to what is going wrong and new ways of intervening.” For instance, he found an unexpected metabolic marker, called formate, that seems to have a role in regulating blood pressure. Little is known about its effects, but changing its levels, possibly through diet or with different gut bacteria, might help to control high blood pressure.

Another of Dr Nicholson’s studies has even found a measurable difference between people who say they like chocolate and those who are indifferent to it. The research, supported by Nestlé, found apparent health benefits too. Not only did chocolate-lovers have lower levels of “bad” LDL cholesterol, but their guts were less likely to harbour the pathogenic bacterium Clostridium difficile, which kills thousands of people a year in hospitals.

Turning such intriguing findings into useful tests will take time. Thousands of people need to be tested and monitored for years to build up an accurate picture of what sort of metabolic patterns could make people ill. But the work has begun: the Human Serum Metabolome Project at Manchester University is collecting samples from over 5,000 people.

Some researchers believe that it will eventually be possible for a device that contains a single computer chip to analyse all the -omes. But that too will take a while to appear. At the moment it is possible to analyse only between 50-100 metabolites at a time, instead of the thousands a device would have to cope with. In the meantime, metabolomics will consist of individual tests—such as one to discover if chocolate is good for you.

RitaA
Posts: 2768
Joined: Thu 1 Jul 2010 8:33

Re: Metabolomics

Post by RitaA » Mon 1 Apr 2013 2:35

A few articles have been published about metabolomics since Joe Ham created this thread in 2008, and I thought I'd share a few of them with anyone who might be interested. Let's start with the definition:

http://whatis.techtarget.com/definition/metabolomics
Metabolomics is a term sometimes used to describe the emerging science of measurement and analysis of metabolites, such as sugars and fats, in the cells of organisms at specific times and under specific conditions. The field of metabolomics overlaps with biology, chemistry, mathematics, and computer science.

Metabolomics as a discipline makes use of analytical processes such as spectroscopy, chromatography, and multivariable analysis. Metabolomics allows scientists to measure physiological effects and to monitor for adverse reactions to drugs. Metabolomics is of interest to physicians because it may lead to improvements in the diagnosis and treatments of human diseases.
For a more in-depth description/understanding of metabolomics:

http://cfgbc.mf.uni-lj.si/people/damjan ... 2009-3.pdf

Here are the links and article abstracts:

http://www.ncbi.nlm.nih.gov/pubmed/20020774
ACS Chem Biol. 2010 Jan 15;5(1):91-103. doi: 10.1021/cb900271r.

Exploring disease through metabolomics.

Vinayavekhin N, Homan EA, Saghatelian A.

Source

Harvard University, 12 Oxford St., Cambridge, Massachusetts 02138, USA.

Abstract

Metabolomics approaches provide an analysis of changing metabolite levels in biological samples. In the past decade, technical advances have spurred the application of metabolomics in a variety of diverse research areas spanning basic, biomedical, and clinical sciences. In particular, improvements in instrumentation, data analysis software, and the development of metabolite databases have accelerated the measurement and identification of metabolites. Metabolomics approaches have been applied to a number of important problems, which include the discovery of biomarkers as well as mechanistic studies aimed at discovering metabolites or metabolic pathways that regulate cellular and physiological processes. By providing access to a portion of biomolecular space not covered by other profiling approaches (e.g., proteomics and genomics), metabolomics offers unique insights into small molecule regulation and signaling in biology. In the following review, we look at the integration of metabolomics approaches in different areas of basic and biomedical research, and try to point out the areas in which these approaches have enriched our understanding of cellular and physiological biology, especially within the context of pathways linked to disease.

PMID: 20020774 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/pubmed/20143941
Future Microbiol. 2010 Feb;5(2):153-61. doi: 10.2217/fmb.09.132.

Metabolomics: towards understanding host-microbe interactions.

Han J, Antunes LC, Finlay BB, Borchers CH.

Source

University of Victoria - Genome BC Proteomics Centre, 3101-4464 Markham Street, Victoria, BC, V8Z 7X8, Canada.

Abstract

Metabolomics employs an array of analytical techniques, including high-resolution nuclear magnetic resonance spectroscopy and mass spectrometry, to simultaneously analyze hundreds to thousands of small-molecule metabolites in biological samples. In conjunction with chemoinformatics and bioinformatics tools, metabolomics enables comprehensive characterization of the metabolic phenotypes (metabotypes) of the human, and other mammalian, hosts that have co-evolved with a large number of diverse commensal microbes, especially in the intestinal tract. Correlation of the metabotypes with the microbial profiles derived from culture-independent molecular techniques is increasingly helping to decipher inherent and intimate host-microbe relationships. This integrated, systems biology approach is improving our understanding of the molecular mechanisms underlying multilevel host-microbe interactions, and promises to elucidate the etiologies of human disorders resulting from unfavorable human-microbial associations, including enteric infections.

PMID: 20143941 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/pubmed/21282433
Antimicrob Agents Chemother. 2011 Apr;55(4):1494-503. doi: 10.1128/AAC.01664-10. Epub 2011 Jan 31.

Effect of antibiotic treatment on the intestinal metabolome.

Antunes LC, Han J, Ferreira RB, Lolić P, Borchers CH, Finlay BB.

Source

Michael Smith Laboratories, The University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada.

Abstract

The importance of the mammalian intestinal microbiota to human health has been intensely studied over the past few years. It is now clear that the interactions between human hosts and their associated microbial communities need to be characterized in molecular detail if we are to truly understand human physiology. Additionally, the study of such host-microbe interactions is likely to provide us with new strategies to manipulate these complex systems to maintain or restore homeostasis in order to prevent or cure pathological states. Here, we describe the use of high-throughput metabolomics to shed light on the interactions between the intestinal microbiota and the host. We show that antibiotic treatment disrupts intestinal homeostasis and has a profound impact on the intestinal metabolome, affecting the levels of over 87% of all metabolites detected. Many metabolic pathways that are critical for host physiology were affected, including bile acid, eicosanoid, and steroid hormone synthesis. Dissecting the molecular mechanisms involved in the impact of beneficial microbes on some of these pathways will be instrumental in understanding the interplay between the host and its complex resident microbiota and may aid in the design of new therapeutic strategies that target these interactions.

PMID: 21282433 [PubMed - indexed for MEDLINE] PMCID: PMC3067180 Free PMC Article
http://www.ncbi.nlm.nih.gov/pubmed/22533566
Bioanalysis. 2012 May;4(8):919-25. doi: 10.4155/bio.12.61.

Metabolomic investigations of human infections.

Pacchiarotta T, Deelder AM, Mayboroda OA.

Source

LUMC, Biomolecular Mass Spectrometry Unit, Leiden University Medical Centre, L4-Q, PO Box 9600, 2300RC Leiden, The Netherlands.

Abstract

Metabolomics has a special place among other 'omics' disciplines (genomics, transcriptomics and proteomics) as it describes the most dynamic level of biological regulation and, as such, provides the most direct reflection of the physiological status of an organism. Quick development of the analytical technologies in the first place - MS and NMR - has enabled the metabolomics analysis of such complex biological phenomena as host-pathogen interactions in the development of infection. In this review, an overview of the metabolomics studies of infectious diseases carried out on human material is provided. The relevant papers on the metabolomics of human infectious diseases are comprehensively summarized in a table, including, for example, information on the study design, number of subjects, employed technology and metabolic discriminator. Future considerations, such as importance of the time-resolved study designs and the embedment of metabolomics in large-scale epidemiological studies are discussed.

PMID: 22533566 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/pubmed/22633095
Transl Res. 2012 Jun;159(6):430-53. doi: 10.1016/j.trsl.2011.12.009. Epub 2012 Jan 15.

Translational research in infectious disease: current paradigms and challenges ahead.

Fontana JM, Alexander E, Salvatore M.

Source

Department of Public Health, Weill Cornell Medical College, New York, NY 10065, USA.

Abstract

In recent years, the biomedical community has witnessed a rapid scientific and technologic evolution after the development and refinement of high-throughput methodologies. Concurrently and consequentially, the scientific perspective has changed from the reductionist approach of meticulously analyzing the fine details of a single component of biology to the "holistic" approach of broadmindedly examining the globally interacting elements of biological systems. The emergence of this new way of thinking has brought about a scientific revolution in which genomics, proteomics, metabolomics, and other "omics" have become the predominant tools by which large amounts of data are amassed, analyzed, and applied to complex questions of biology that were previously unsolvable. This enormous transformation of basic science research and the ensuing plethora of promising data, especially in the realm of human health and disease, have unfortunately not been followed by a parallel increase in the clinical application of this information. On the contrary, the number of new potential drugs in development has been decreasing steadily, suggesting the existence of roadblocks that prevent the translation of promising research into medically relevant therapeutic or diagnostic application. In this article, we will review, in a noninclusive fashion, several recent scientific advancements in the field of translational research, with a specific focus on how they relate to infectious disease. We will also present a current picture of the limitations and challenges that exist for translational research, as well as ways that have been proposed by the National Institutes of Health to improve the state of this field.

Copyright © 2012 Mosby, Inc. All rights reserved.

PMID: 22633095 [PubMed - indexed for MEDLINE] PMCID: PMC3361696 [Available on 2013/6/1]
http://www.ncbi.nlm.nih.gov/pubmed/23210853
Curr Med Chem. 2013 Jan 1;20(2):257-71.

Metabolomics analysis for biomarker discovery: advances and challenges.

Monteiro MS, Carvalho M, Bastos ML, de Pinho PG.

Source

REQUIMTE, Laboratório de Toxicologia, Faculdade de Farmácia, Universidade do Porto, Rua Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal.

Abstract

Over the last decades there has been a change in biomedical research with the search for single genes, transcripts, proteins, or metabolites being substituted by the coverage of the entire genome, transcriptome, proteome, and metabolome with the "omics" approaches. The emergence of metabolomics, defined as the comprehensive analysis of all metabolites in a system, is still recent compared to other "omics" fields, but its particular features and the improvement of both analytical techniques and pattern recognition methods has contributed greatly to its increasingly use. The feasibility of metabolomics for biomarker discovery is supported by the assumption that metabolites are important players in biological systems and that diseases cause disruption of biochemical pathways, which are not new concepts. In fact, metabolomics, meaning the parallel assessment of multiple metabolites, has been shown to have benefits in various clinical areas. Compared to classical diagnostic approaches and conventional clinical biomarkers, metabolomics offers potential advantages in sensitivity and specificity. Despite its potential, metabolomics still retains several intrinsic limitations which have a great impact on its widespread implementation - these limitations in biological and experimental measurements. This review will provide an insight to the characteristics, strengths, limitations, and recent advances in metabolomics, always keeping in mind its potential application in clinical/ health areas as a biomarker discovery tool.

PMID: 23210853 [PubMed - in process]

RitaA
Posts: 2768
Joined: Thu 1 Jul 2010 8:33

Re: Metabolomics

Post by RitaA » Mon 1 Apr 2013 2:48

Here's one example of metabolic changes that may be very relevant to Lyme disease:

http://www.ncbi.nlm.nih.gov/pubmed/12124483
Nucl Med Commun. 2002 Aug;23(8):773-7.

Cerebral metabolic changes associated with Lyme disease.

Newberg A, Hassan A, Alavi A.

Source

Division of Nuclear Medicine, Hospital of the University of Pennsylvania, 110 Donner Building, 3400 Spruce Street, Philadelphia, PA 19104, USA

Abstract

There are no positron emission tomography (PET) studies reported in the literature with regards to brain metabolism and function in patients with Lyme disease. These patients frequently present with various neurological symptoms, including memory problems. We used [(18)F]fluorodeoxyglucose (FDG) PET to determine the metabolic landscape in 23 patients with Lyme disease. Images were evaluated for cortical and subcortical abnormalities by two experienced reviewers blinded to the clinical information. The most striking finding was hypometabolism in the temporal lobes in 17/23 (74%) patients. Of these, 12 had bilateral temporal lobe hypometabolism, two had left temporal lobe, and three had right temporal lobe hypometabolism. Seven of the patients with temporal lobe hypometabolism had diffuse cortical hypometabolism that included the frontal and parietal lobes. Lyme disease appears to have two primary patterns of brain involvement on FDG PET scans, specific temporal lobe hypometabolism or a diffuse cortical hypometabolism. The involvement of the temporal lobes in both patterns is likely associated with the memory disturbances described in many of these patients. Although there was no clear diagnostic pattern, and many of the defects were mild, FDG PET imaging may provide important information regarding the areas of the brain affected in patients with neurological symptoms associated with Lyme disease.

PMID: 12124483 [PubMed - indexed for MEDLINE]
These results may not be specific to Lyme disease by any means, however this type of data could prove useful when trying to narrow down diagnostic possibilities. An abnormal PET imaging result provides objective data to support what might otherwise be dismissed as a patient's purely subjective experience of cognitive difficulties.

RitaA
Posts: 2768
Joined: Thu 1 Jul 2010 8:33

Re: Metabolomics

Post by RitaA » Mon 8 Apr 2013 23:58

Thanks, Camp Other, for tweeting about this:

http://scopeblog.stanford.edu/2013/04/0 ... e-disease/
IN THE NEWS, MICROBIOLOGY, RESEARCH

Could “breathprints” one day be used to diagnose disease?

Lia Steakley on April 5th, 2013

Your “breathprint,” the chemical composition of each exhale, may hold potential as a new medical diagnostic tool, according to research recently published in PLOS ONE.

In the small study, Swiss researchers used a technique known as mass spectrometry to analyze the molecules in participants’ breath samples. As reported in the New Scientist:

The team was interested in metabolites, compounds produced by the body’s metabolism. The molecules are volatile and small enough to pass from the blood into airways via the alveoli in our lungs, so are present in our breath – albeit in miniscule amounts, sometimes less than one molecule per billion molecules of air.

The team found that metabolites in individuals’ breath remained “constant and clear”, says Swiss Federal Institute of Technology professor [Renato Zenobi, PhD].

Zenobi’s team can identify compounds in breath immediately, so our breathprint could be used to detect signature metabolites associated with disease, giving an instant diagnosis. In a preliminary study, Zenobi has shown that breath samples can reveal whether people have chronic obstructive pulmonary disease.

While more research is needed to understand how breathprints might be used in a clinical setting, the research is noteworthy in light of the growing body of scientific showing a variety of unique biological identifiers, including microscopic ecosystems that exist in the human body, could offer insights into our personal health.
http://www.newscientist.com/article/dn2 ... print.html

http://www.plosone.org/article/info%3Ad ... ne.0059909
RESEARCH ARTICLE

Human Breath Analysis May Support the Existence of Individual Metabolic Phenotypes

Abstract

The metabolic phenotype varies widely due to external factors such as diet and gut microbiome composition, among others. Despite these temporal fluctuations, urine metabolite profiling studies have suggested that there are highly individual phenotypes that persist over extended periods of time. This hypothesis was tested by analyzing the exhaled breath of a group of subjects during nine days by mass spectrometry. Consistent with previous metabolomic studies based on urine, we conclude that individual signatures of breath composition exist. The confirmation of the existence of stable and specific breathprints may contribute to strengthen the inclusion of breath as a biofluid of choice in metabolomic studies. In addition, the fact that the method is rapid and totally non-invasive, yet individualized profiles can be tracked, makes it an appealing approach.

Citation: Martinez-Lozano Sinues P, Kohler M, Zenobi R (2013) Human Breath Analysis May Support the Existence of Individual Metabolic Phenotypes. PLoS ONE 8(4): e59909. doi:10.1371/journal.pone.0059909

Editor: Pal Bela Szecsi, Gentofte University Hospital, Denmark

Received: October 29, 2012; Accepted: February 22, 2013; Published: April 3, 2013

Copyright: © 2013 Martinez-Lozano Sinues et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Funding: This research was supported by a Marie Curie European Reintegration Grant (PMLS) within the 7th European Community Framework Programme (276860). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.

Introduction

Personalized medicine aims to tailor medical treatment to the individual characteristics of each patient [1]. With the advent of high-throughput genome sequencing techniques, the concept of personalized health care is about to become a reality in the clinic [2]. However, the genome alone cannot account for factors like life style, interplay with gut microbiome [3] or circadian cycle [4]–[6]. For this reason, mapping of the metabolome and relating it to sub-populations or even individuals will be critical to fully achieve the concept of personalized healthcare [7]. However, precisely because the metabolome accounts for external factors, it is subject to intra-individual variations that need to be characterized. To address this issue, recent studies have investigated the question whether individual metabolic phenotypes are stable during extended periods of time [8], [9].

As other biofluids, breath contains relevant biochemical information, since it carries a large fraction of the most volatile metabolites [10]. Breath analysis is completely non-invasive, and therefore an attractive approach, which in principle is also suitable to monitor an individual's health status over extended periods of time. However, breath analysis has not yet been routinely used to complement the analysis of other biofluids in order to contribute to an individualized healthcare. This situation may start to be reversed by the assessment of the intra-individual variations of the composition of human breath; and ultimately examining whether or not individualized breathprints persist over the time. This has been the main goal of the present study.
And let's not forget to give credit to our four-legged friends:

http://www.nytimes.com/2011/07/03/busin ... .html?_r=0
Novelties

Beyond the Breathalyzer: Seeking Telltale Signs of Disease

By ANNE EISENBERG
Published: July 2, 2011

[snip]

Scientists are building sophisticated electronic and chemical sniffers that examine the puffs of exhaled air for telltale signs of cancer, tuberculosis, asthma and other maladies, as well as for radiation exposure.

“There are clear signatures in the breath for liver disease, kidney disease, heart disease” and diseases of the lungs, said Dr. Raed Dweik, director of the pulmonary vascular program at the Cleveland Clinic, who studies breath analysis. “My sense is that breath analysis is the future of medical testing, complementing many of the blood and imaging steps we do today.”

“Breath is a rich matrix that can reflect our state of health or disease,” Dr. Dweik said. In fact, he observed, breath is so rich in chemical compounds that fully understanding it has proved challenging. Each exhalation contains gases like carbon dioxide, of course, but also the volatile remains of recent snacks, medicines and even compounds inhaled from things like carpeting, upholstery or various kinds of air pollution.

But monitors can sort out these exhaled substances with increasing sensitivity, bringing breath analysis closer to widespread use as a noninvasive tool in medical diagnosis and treatment.

[snip]

AT the Cleveland Clinic, Dr. Peter Mazzone is analyzing the breath of patients to determine whether they have lung cancer. In his test, breath is drawn across sensors that change color and are then captured on digital cameras. The patterns are then compared with those of people without the disease. His tests have reached 85 percent accuracy so far in spotting people with the illness, he said.

But some trained dogs, he pointed out, can sniff out cancer with 99 percent accuracy — although without, for example, the ability to identify particular compounds the way some analyzers can.

“We are getting better and better,” he said. “But whether we will ever approach the accuracy of the dog — we don’t know.”

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