The Intestinal Metabolome: An Intersection Between Microbiota and Host

Ursell, Luke K.; Haiser, Henry J.; Treuren, Will Van; Garg, Neha; Reddivari, Lavanya; Vanamala, Jairam; Dorrestein, Pieter C.; Turnbaugh, Peter J.; Knight, Rob

doi:10.1053/j.gastro.2014.03.001

Cited by 293 publications

(219 citation statements)

References 56 publications

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“…In addition to CNS-induced changes in the gut environment, signaling molecules used by the host for neuronal and neuroendocrine signaling, including but not limited to catecholamines, serotonin, dynorphin, GABA, and cytokines, may also be released into the gut lumen by neurons, immune cells, and enterochromaffin cells (98,114 The main effect of the gut microbiota perturbations on the brain may occur at times of lower diversity and instability of the gut microbiota (infants and the elderly) (136)(137)(138) and during brain development (perinatal and infant period) (139). During the prenatal period, the developing brain is first exposed to maternal gut-derived metabolites and may be exposed to intrauterine microbes (61).…”

Section: Effect Of Interventions Targeting the Gut Microbiotamentioning

confidence: 99%

Gut/brain axis and the microbiota

Mayer¹,

Tillisch²,

Gupta³

2015

J. Clin. Invest.

1,143

824

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Section: Effect Of Interventions Targeting the Gut Microbiotamentioning

confidence: 99%

Gut/brain axis and the microbiota

Mayer¹,

Tillisch²,

Gupta³

2015

J. Clin. Invest.

1,143

824

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“…The overall role of the gut microbiome in health and disease is increasingly being appreciated (Owyang and Wu, 2014;Ursell et al, 2014; C. D. Klaassen and J. Y. Cui, submitted manuscript), as is the contribution of gut bacteria to the metabolism of drugs (Sousa et al, 2008). Our own experience with BILR 355 and Fig.…”

Section: Discussionmentioning

confidence: 98%

Defining the Role of Gut Bacteria in the Metabolism of Deleobuvir: In Vitro and In Vivo Studies

et al. 2015

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Deleobuvir is a potent inhibitor of the hepatitis C virus nonstructural protein 5B polymerase. In humans, deleobuvir underwent extensive reduction to form CD 6168. This metabolite was not formed in vitro in aerobic incubations with human liver microsomes or cytosol. Anaerobic incubations of deleobuvir with rat and human fecal homogenates produced CD 6168. Using these in vitro formation rates, a retrospective analysis was conducted to assess whether the fecal formation of CD 6168 could account for the in vivo levels of this metabolite. The formation of CD 6168 was also investigated using a pseudo-germ free (pGF) rat model, in which gut microbiota were largely eradicated by antibiotic treatment. Plasma exposure (area under the curve from 0 to ') of CD 6168 was approximately 9-fold lower in pGF rats (146 6 64 ng·h/ml) compared with control rats (1,312 6 649 ng·h/ml). Similarly, in pGF rats, lower levels of CD 6168 (1.5% of the deleobuvir dose) were excreted in feces compared with control rats (42% of the deleobuvir dose). In agreement with these findings, in pGF rats, approximately all of the deleobuvir dose was excreted as deleobuvir into feces (105% of dose), whereas only 26% of the deleobuvir dose was excreted as deleobuvir in control rats. These differences in plasma and excretion profiles between pGF and control rats confirm the role of gut bacteria in the formation of CD 6168. These results underline the importance of evaluating metabolism by gut bacteria and highlight experimental approaches for nonclinical assessment of bacterial metabolism in drug development.

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“…Estudos da evolução, fisiologia e bioquímica desses organismos estão intimamente relacionados aos sistemas biológicos e assim, a metabolômica, juntamente com as outras ciências ômicas, tem um papel fundamental na compreensão dos fenômenos biológicos ocorridos na microbiologia. 170 A metabolômica tem sido aplicada a organismos microbianos, especialmente estudos relacionados ao metabolismo da microbiota intestinal [171][172][173][174][175] 187 e busca por alimentos funcionais, como os probióticos. 188,189 Um segmento novo e que vem sendo explorado na indústria e estudado pelas ciências ômicas é o processo de biolixiviação, que consiste na conversão de metais, frutos de rejeitos industriais, catalisada por microorganismos.…”

Section: Microbiologiaunclassified

Metabolômica: Definições, Estado-Da-Arte E Aplicações Representativas

Canuto¹,

Costa²,

Cruz³

et al. 2017

Quim. Nova

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METABOLOMICS: DEFINITIONS, STATE-OF-THE-ART AND REPRESENTATIVE APPLICATIONS.Metabolomics is an emerging and promising omics approach used to understand biological mechanisms. By untargeted and targeted metabolomics analyses, metabolites are determined in biological samples (fluids, cells, tissues, etc.) by comparison of control groups with altered groups, undergoing different therapies, submitted to differing stress levels, dietary modulation, or promoted by a disease, or specific condition, etc., using sophisticated analytical techniques, and advanced data treatment and statistical analyses. In this review, the concepts involved in metabolomics studies were presented, describing in details all steps involved in the metabolomics workflow, for untargeted and targeted strategies. Finally, the potential of metabolomics is illustrated by applications in representative areas: clinical, environmental, food and nutrition, forensic toxicology, microbiology, parasitology, plants, and sports. Relevant reviews were compiled to characterize each of these areas, and a corresponding application of untargeted and targeted metabolomics were described.Keywords: metabolomics; untargeted metabolomics; targeted metabolomics; metabolomics workflow. INTRODUÇÃOAs ciências ômicas buscam o entendimento do funcionamento celular dos organismos e suas alterações biológicas. Fazem parte deste conjunto de ciências, a genômica (estudo da alteração dos genes), a transcriptômica (estudo das alterações dos transcritos), a proteômica (estudo das alterações das proteínas), e a metabolômica (estudo das alterações dos metabólitos). Metabólitos são produtos intermediários ou finais do metabolismo em uma amostra biológica.1 O conjunto de todos os metabólitos de baixa massa molecular (até 1500 Da), presentes ou alterados em um sistema biológico, é chamado de metaboloma (do inglês, metabolome).2 A pesquisa relacionada a metabólitos vem sendo desenvolvida há décadas, mas em 1999, Nicholson et al. definiram a metabonômica (do inglês, metabonomics), como sendo a medida quantitativa da resposta metabólica de um sistema biológico após estímulos fisiopatológicos ou modificações genéticas.3 Já o termo metabolômica (do inglês, metabolomics) foi introduzido em 2001, por Oliver Fiehn, como sendo a análise abrangente e quantitativa do metaboloma de um sistema biológico. 4 Além disso, a literatura nos apresenta outras denominações envolvendo esse campo da ciência, tais como: perfil metabólico (do inglês, metabolic profiling), descrito como sendo a análise de metabólitos previamente selecionados de rotas bioquímicas específicas, 5 a impressão digital metabólica (do inglês, metabolic fingerprinting), que é definida como sendo "uma classificação de amostras de acordo com sua origem ou sua relevância biológica", 3 e, por último, análise footprinting (ainda sem tradução para o português), para se referir aos metabólitos excretados por uma célula em condições controladas. Observa-se, portanto, uma divergência em relação às terminologias aplicadas às análises metabolômic...

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The Intestinal Metabolome: An Intersection Between Microbiota and Host

Cited by 293 publications

References 56 publications

Gut/brain axis and the microbiota

Gut/brain axis and the microbiota

Defining the Role of Gut Bacteria in the Metabolism of Deleobuvir: In Vitro and In Vivo Studies

Metabolômica: Definições, Estado-Da-Arte E Aplicações Representativas

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