The microbiome in health and disease

Omry Koren, PhD

Azrieli Faculty of Medicine

Bar Ilan University6 December 2019

Bad guys?

Who’s good and who’s bad?

100 Trillion Little Friends

• 10 times more microbialcells than human cells onthe human body

• Majority in large intestine

• Provide enhancednutrition and protectionagainst pathogens

Dysbiosis - Shifts in the Microbiome

Neuman and Koren, Encyclopedia of Cell Biology

Our diet is changing

Our diet is changing

Mouse Models Help Us Learn More

Leptin: A hormone, produced by adipose tissue, that plays a key role in regulating appetite and metabolism

mutantnormal

(without leptin)(with leptin)

Altered gut microbiome in leptin-deficient mice

Firmicutes

Bacteroidetes

% S

equ

ence

s

Ley et al., PNAS 102: 11070-5 (2005)

mutantnormal

mutantnormal

(without leptin)(with leptin)

Microbiome Transplants – a Powerful Tool

Microbiota transplantation experiments

mutantnormalConventionally raised donors

Germ-free normalrecipients

Donor

Turnbaugh et al., Nature 444: 1027-1031 (2006)

An altered microbiome in obesity

12 HUMANS

1-year (4 time points)Ley, 2006

Twins

Bacteria may help keep you lean

Goodrich et al. Cell, 2014

Neuman and Koren, Encyclopedia of Cell biology

Phenotype Effect: Microbiota Transfer

Phenotype Effect: Microbiota Transfer

Nuriel-Ohayon et al., Cell Reports 2019

What about the kids?

Adapted from Fischer et al. 2012

We are inoculated at birth

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NATURE MEDICINE I BRI CO UNICA ON

Partial restoration of the microbiota of cesarean­born infants via vaginal microbial transfer

Maria G Do i guez-Be lo, Kassandra De Jes s- aboy, a Shen, La ra Cox, Amnon

Amir, A tonio Gonzalez, icholas A Boku ·ch, Se J'n Song, ar·na oash·, J a a ivera­

Vinas, Keimari Mendez, Rob Kn·g & Jose CC eme te

A thations I Contribuf ons I Corresponding a t ors

Nature Medicine (2016) I doi:10.1038/nm.4039

Received 03 July 2015 I Accep ed 22 December 2015 I Published online 01 February 2016

We are inoculated at birth