Andrés Moya

XXXVI Lección Memorial Fernández Cruz

“Retrasa tu reloj biológico”

“Turn back your biological clock”

Madrid, 20 de Septiembre de 2017

Microbiota, salud y envejecimiento

Microbiota, health and aging

Microbioma humano

Microbioma: salud, enfermedad y envejecimiento

Convergent evolution of the host epithelial interface with the microbiota

Foster et al., Nature, 2017

Human Coral-relative Hydra Plant

Human to bacterial cell ratio

Rough estimates of size and biodiversityin an adult body

1/3 of the total microbiota is common to most people2/3 is specific to each individual

Rojo et al., FEMS Microbial Reviews, 2017

Microbiota composition and physiological conditions along the digestive tract

The Epigenetic Landscape (Waddington 1957)

Development

Zygote

Different Phenotypes

Functional stability against disturbance

Eubiosis

Dysbiosis

The microbiome landscape

Lloyd-Price et al., Genome Medicine, 2016Moya and Ferrer, Trends in Microbiology, 2016

Onset and shaping of microbiota through life stages and perturbations

Exploring the human microbiome from multiple

perspectives: factors altering its composition and

function

Rojo et al., FEMS Microbial Reviews, 2017

Diseases and disorders associated with alterations to the total of microbiota

28 types of disease105 diseases231 non-redundant genera, 15 different phyla12 genera associated with at least 50% of diseases

Local and external factors (covariates) associated with alterations to the total

microbiota

21 covariates130 genera, 13 different phyla12 genera are also associated with al least 50% of the covariates

Antibiotics associated with alterations in total microbiota

42 microbial genera altered after treatment with68 antibiotic therapies

Microbial metabolite biomarkers found to discrimate healthy controls and

patients: 621 metabolites

40% of the human metabolites are of microbial origin

Three key metabolisms associated to multiple factors

There is a goodcorrelation between changesin the microbiota and metabolicprofile (r2 = 0.534, p value = 0.00017)

Many metabolites whose abundancelevel was altered are associated withmultiple perturbations

Clustering of the metabolic biomarkers and gut microbiota active members in the

context of multiple diseases and interventions

Bacteria that actively participate in the metabolism of these molecules

Health and disease imprinted in the time variability of the

human microbiome

Martí et al. mSystems, 2017

Power law fits (Taylor law) of the standard deviation (SD) vs. mean of relative abundance of bacterial genus

monitored over time

Healthy subject

IBS subject

Taylor’s law parameter space for different studies

98%CL

68%CL

Microbiota states can be placed in the phase space F (Fitness)-V (Variability)

Indoles from commensal bacteria extend healthspan

Sonowal et al., PNAS, 2017

Commensal E. coli-derived indole extends lifespan and healthspan in C. elegans and

D. melanogaster

C. elegans

D. melanogaster

The aryl hydrocarbon receptor (AHR) mediates effects of indoles on healthspan

Indole from comensal E. coli augments lifespanand extends healthspan of mice

Summary

1/3 of our microbiota is common to most people, while2/3 are specific to each individual.

To date, 105 diseases and disorders are associated withchanges in gut, respiratory, oral, skin and urinary/vaginalmicrobiotas.

40% of metabolites in the human body are produced byour microbiota.

A fluctuation scaling law describe the temporal changes inthe gut microbiota.

Stable microbiotas can be distinguished from unstablemicrobiotas.

Indole from commensal bacteria extend healthspan.

Muchas gracias por su atención