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The newest "omics"--metagenomics and metabolomics--enter the battle against the neglected tropical diseases.

Preidis GA, Hotez PJ - PLoS Negl Trop Dis (2015)

View Article: PubMed Central - PubMed

Affiliation: Section of Gastroenterology, Hepatology & Nutrition, Department of Pediatrics, Baylor College of Medicine and Texas Children's Hospital, Houston, Texas, United States of America.

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Metagenomic analyses are most often undertaken by sequencing the bacterial 16S ribosomal RNA (rRNA) subunit or by whole metagenome shotgun sequencing, typically on a massively parallel pyrosequencing platform... These technologies have expanded the scope of traditional culture-dependent microbiological methods and have enhanced our understanding of the rich microbial communities that inhabit the intestine, skin, oral cavity, and genitourinary tract and how these commensal microbes interact with both pathogen and host... Today’s commonly employed methods fall under one of two categories, the first of which is sequencing the 16S ribosomal RNA gene subunit... A parasite’s endosymbiotic bacteria can play integral roles in the pathogenesis of disease... This concept was demonstrated decades ago, with doxycycline eradication of Wolbocchia spp. in Onchocerca volvulus effectively sterilizing adult worms... As improvements in sequencing and microbial identification develop, new methods of surveillance and diagnosis will merit testing in the field... Metabolites produced by microbial and host cells contain an extraordinary array of physicochemical properties, may be present in virtually any body tissue or fluid, and are found in concentrations differing by multiple orders of magnitude... Both of these approaches are dependent on sample preparation methods that introduce bias and inevitably metabolite losses... Alternatively, nuclear magnetic resonance (NMR) spectroscopy does not require prior separation of compounds within a sample, although minimizing sample preparation comes at a cost in terms of resolution; NMR can usually only detect compounds at or above a millimolar level... Moreover, a fully annotated, comprehensive metabolite library, especially for microbial-derived compounds, is still many years away... Early metabolomic studies revealed that small changes in the intestinal compartment have profound effects on host metabolites measured outside of the intestine... Only 25 of these metabolites were among the 126 significantly altered metabolites comparing acute versus antibiotic-treated intensive care unit patients with S. aureus sepsis... Nonetheless, a subset of the 25 metabolites common to inbred mouse and clinical studies successfully predicted treatment response in humans... Finally, autopsy specimens revealed abnormal patterns of inflammation and anaerobic metabolism in the brain of an elderly individual who died despite receiving the standard postexposure neuroprotection for rabies, the strain of which was identified using deep sequencing of host RNA... We ultimately seek to understand how specific microbes contribute to nutritional status, how metabolic profiles contribute to disease pathogenesis, and how manipulation of either may influence the host response to infection.

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Metabolomic profiles in parasitism.
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pntd.0003382.g002: Metabolomic profiles in parasitism.

Mentions: Early metabolomic studies revealed that small changes in the intestinal compartment have profound effects on host metabolites measured outside of the intestine. Manipulation of the mouse intestinal microbiome altered the metabolome in every tissue or biofluid analyzed [44,45]. Similarly, Fasciola hepatica infection in rats induced metabolic changes in areas as remote from the liver as brain tissue. Metabolic profile differences were manifest in altered concentrations of neural nucleotides; specifically, brains of infected rats had increased concentrations of inosine, tyrosine, and phenylalanine and decreased levels of glycerophosphocholine, succinate, inosine mono-, di-, and triphosphate, adenosine, and adenosine mono-, di-, and triphosphate compared to controls [46]. Such evidence could provide the basis for neurological sequelae of some helminth infections, even in the absence of direct invasion of brain parenchyma. For example, could metabolite alterations partially account for the cognitive disturbances linked to pediatric gastrointestinal nematode or schistosome infections in developing countries [47–49] or the common parasitic infections in North America linked to brain dysfunction [50]? Still another worthwhile avenue for metabolomic investigations is the potentially altered profiles in both humans and animals with wasting syndromes and growth deficits linked to some chronic helminth and protozoan infections, including hookworm and other gastrointestinal helminths, schistosomiasis, leishmaniasis, and trypanosomiasis (Fig. 2) [51–54].


The newest "omics"--metagenomics and metabolomics--enter the battle against the neglected tropical diseases.

Preidis GA, Hotez PJ - PLoS Negl Trop Dis (2015)

Metabolomic profiles in parasitism.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4326130&req=5

pntd.0003382.g002: Metabolomic profiles in parasitism.
Mentions: Early metabolomic studies revealed that small changes in the intestinal compartment have profound effects on host metabolites measured outside of the intestine. Manipulation of the mouse intestinal microbiome altered the metabolome in every tissue or biofluid analyzed [44,45]. Similarly, Fasciola hepatica infection in rats induced metabolic changes in areas as remote from the liver as brain tissue. Metabolic profile differences were manifest in altered concentrations of neural nucleotides; specifically, brains of infected rats had increased concentrations of inosine, tyrosine, and phenylalanine and decreased levels of glycerophosphocholine, succinate, inosine mono-, di-, and triphosphate, adenosine, and adenosine mono-, di-, and triphosphate compared to controls [46]. Such evidence could provide the basis for neurological sequelae of some helminth infections, even in the absence of direct invasion of brain parenchyma. For example, could metabolite alterations partially account for the cognitive disturbances linked to pediatric gastrointestinal nematode or schistosome infections in developing countries [47–49] or the common parasitic infections in North America linked to brain dysfunction [50]? Still another worthwhile avenue for metabolomic investigations is the potentially altered profiles in both humans and animals with wasting syndromes and growth deficits linked to some chronic helminth and protozoan infections, including hookworm and other gastrointestinal helminths, schistosomiasis, leishmaniasis, and trypanosomiasis (Fig. 2) [51–54].

View Article: PubMed Central - PubMed

Affiliation: Section of Gastroenterology, Hepatology & Nutrition, Department of Pediatrics, Baylor College of Medicine and Texas Children's Hospital, Houston, Texas, United States of America.

AUTOMATICALLY GENERATED EXCERPT
Please rate it.

Metagenomic analyses are most often undertaken by sequencing the bacterial 16S ribosomal RNA (rRNA) subunit or by whole metagenome shotgun sequencing, typically on a massively parallel pyrosequencing platform... These technologies have expanded the scope of traditional culture-dependent microbiological methods and have enhanced our understanding of the rich microbial communities that inhabit the intestine, skin, oral cavity, and genitourinary tract and how these commensal microbes interact with both pathogen and host... Today’s commonly employed methods fall under one of two categories, the first of which is sequencing the 16S ribosomal RNA gene subunit... A parasite’s endosymbiotic bacteria can play integral roles in the pathogenesis of disease... This concept was demonstrated decades ago, with doxycycline eradication of Wolbocchia spp. in Onchocerca volvulus effectively sterilizing adult worms... As improvements in sequencing and microbial identification develop, new methods of surveillance and diagnosis will merit testing in the field... Metabolites produced by microbial and host cells contain an extraordinary array of physicochemical properties, may be present in virtually any body tissue or fluid, and are found in concentrations differing by multiple orders of magnitude... Both of these approaches are dependent on sample preparation methods that introduce bias and inevitably metabolite losses... Alternatively, nuclear magnetic resonance (NMR) spectroscopy does not require prior separation of compounds within a sample, although minimizing sample preparation comes at a cost in terms of resolution; NMR can usually only detect compounds at or above a millimolar level... Moreover, a fully annotated, comprehensive metabolite library, especially for microbial-derived compounds, is still many years away... Early metabolomic studies revealed that small changes in the intestinal compartment have profound effects on host metabolites measured outside of the intestine... Only 25 of these metabolites were among the 126 significantly altered metabolites comparing acute versus antibiotic-treated intensive care unit patients with S. aureus sepsis... Nonetheless, a subset of the 25 metabolites common to inbred mouse and clinical studies successfully predicted treatment response in humans... Finally, autopsy specimens revealed abnormal patterns of inflammation and anaerobic metabolism in the brain of an elderly individual who died despite receiving the standard postexposure neuroprotection for rabies, the strain of which was identified using deep sequencing of host RNA... We ultimately seek to understand how specific microbes contribute to nutritional status, how metabolic profiles contribute to disease pathogenesis, and how manipulation of either may influence the host response to infection.

No MeSH data available.