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Title: Estabilidad resiliencia y redundancia funcional de la microbiota intestinal humana durante el desarrollo y en respuesta al estrés antibiótico y a Clostridium difficile

Research Group: Evolutionary Genetics

The concept of stable microbiota involves the idea that, after a disturbance, the microbial community returns to its initial position in terms of composition (resilience) or function (functional redundancy) when the disturbing factor disappears.  Through the application of a new method developed in the group, the Complex Cruncher software, and through the determination of the composition (metagenome) and function (metatranscriptome and metabolome) of the intestinal microbiota we can evaluate its stability in a longitudinal study. For that, volunteers from Valencian Community were involved in this study, 10 infants, 10 adults an 10 elderly unrelated and on the other hand cohort of 12 toddlers, 13 adolescents and 35 adults related. For each volunteer between eight and ten fecal samples were collected and all procedures were reviewed and approved by FISABIO. Preliminary results with the unrelated cohort show that the distribution of relative abundances in the fecal microbiota was dominated in all groups by as already described, two phyla, Firmicutes and Bacteroidetes, representing between 80% -90% of the known phylogenetic categories in the human intestine while the Actinobacteria, Proteobacteria, Fusobacteria, Verrucomicrobia and Lentisphaera phyla showed a lower abundance (<1% -18%). Genera or species showed statistically significant differences in their relative abundance between age groups. At the functional level, the “age” factor also would explain the differences observed between the groups. When these comparisons are established between pairs of age groups we observe that the most significant differences are established between the most extreme ages (infants and the elderly). These data are consistent with a significantly greater number of functions, among infants and the elderly (198) than among infants and adults (61) or between adults and the elderly (59) observed in the statistical tests. However, at expression level, the “age” factor would not explain the differences observed between the groups or between pairs of age groups. These data are not consistent with a significantly greater number of functions among infants and the elderly (61) than among infants and adults (27) or between adults and the elderly (127) observed in the statistical tests.  Finally, proteomics and metabolomics studies have identified, among other a relationship between tryptophan and indole metabolism and aging. Indeed, the synthesis of proteins involved in the production of tryptophan and indole and the concentration of these metabolites in faeces are directly related, and progressively decreased with age.

Although the results of the different omics are preliminary the software Complex Cruncher has allowed delimit whether the microbiota is healthy or not with this data, estimating two systemic parameters (amplitude of fluctuation or V and the index of the law of power). The healthy population was defined for now with adults and the elderly being much more stable than infants.

Total amount: 435.600 €
Ref. SAF2015-65878-R

Unión Europea - FEDER Ministerio de Economía y Competitividad

Start date: January / 2016.

End date: December / 2019.

Principal investigators:

Andrés Moya, Pilar Francino


Funding agencies:

FEDER Founds, Ministerio de Economía y Competitividad


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