Stability and Robustness of Human Metabolic Phenotypes in Response to Sequential Food Challenges

Abstract

High-resolution spectroscopic profiles of biofluids can define metabolic phenotypes, providing a window onto the impact of diet on health to reflect gene-environment interactions. (1)H NMR spectroscopic profiling was used to characterize the effect of nutritional intervention on the stability of the metabolic phenotype of 7 individuals following a controlled 7 day dietary protocol. Inter-individual metabolic differences influenced proportionally more of the spectrum than dietary modulation, with certain individuals displaying a greater stability of metabolic phenotypes than others. Correlation structures between urinary metabolites were identified and used to map inter-individual pathway differences. Choline degradation was the pathway most affected by the individual, suggesting that the gut microbiota influence host metabolic phenotypes. This influence was further emphasized by the highly correlated excretion of the microbial-mammalian co-metabolites phenylacetylglutamine, 4-cresylsulfate (r = 0.87), and indoxylsulfate (r = 0.67) across all individuals. Above the background of inter-individual differences, clear biochemical effects of single type dietary interventions, animal protein, fruit and wine intake, were observed; for example, the spectral variance introduced by fruit ingestion was attributed to the metabolites tartrate, proline betaine, hippurate, and 4-hydroxyhippurate. This differential metabolic baseline and response to selected dietary challenges highlights the importance of understanding individual differences in metabolism and provides a rationale for evaluating dietary interventions and stratification of individuals with respect to guiding nutrition and health programmes.

Genetically identical co-housed pigs as models for dietary studies of gut microbiomes

“…While there were shared OTUs that were resistant to change in these pigs, there were also unique OTUs that were very different in their response to diet. These results are in agreement with prior studies reporting that inter-individual differences exerted more influence than differences within an individual in the response to a dietary intervention [60][61][62]. These inter-individual variations most probably resulting from epigenetics are not entirely eliminated by the use of genetically identical cloned pigs.…”

A nonpyrrolysine member of the widely distributed trimethylamine methyltransferase family is a glycine betaine methyltransferase

“…For example, depletion of the GB pool by demethylation could lessen the total amount of TMA produced in the intestine. Dimethylglycine, the direct product of glycine betaine, has been identified in serum and urine and has been sometimes attributed to liver activities (67,68). However, we identified, at the National Center for Biotechnology Information and the Joint Genome Institute-Integrated Microbial Genomes, multiple intestinal or fecal inhabitants having MtgB homologs encoded in their sequenced genomes.…”

Current status on genome–metabolome-wide associations: an opportunity in nutrition research

“…In typical casecontrol studies, frequent in Nutrimetabonomics (Rezzi et al 2007;Martin et al 2009a;Heinzmann et al 2011;van Velzen et al 2008;, the genetic effects on homeostasis regulation may introduce undesired variance in metabolic profiles. These effects may obscure diet-induced metabolic changes, which may be of relatively low magnitude.…”