Download Klinisches Fehler- und Risikomanagement

Worker bee or queen?
On the epigenetics of human breastfeeding
and bonding
Sebastian Hentsch
© Goodisman Research Group
1
Agenda
1. What is epigenetics?
2. Epigenetic effects of bonding
3. Epigenetic effects of
breastfeeding
4. Conclusion
2
What is epigenetics?
• Royal jelly
–
secreted from head glands of worker bees, fed to all bee larvae for 3 days (worker bee, drone),
>3 days (queen)
–
2008: experimental manipulation of DNA-methylation led to develpoment of queens instead do
worker bees [1]
[1] Kucharski R et al.: Nutritional control of reproductive status in honeybees via DNA methylation. Science 319:1827-1830 (2008)
3
What is epigenetics?
3 known epigenetic „switches“
– DNA methylation
– Histone modification
– RNA interference
4
What is epigenetics?
• DNA methylation by DNA methyltransferases
(DNMT)
–
–
–
methylated cytosin represses transcription, gene is „switched off“
Mammalians: 60-80% of Cytosin methylated
almost no methylation: embryonic stem cells, neural
development
5
© http://pinkhope.org.au/epigenetics-dna-methylation-genetics-and-cancer/#.VJmJKf8CAnk
What is epigenetics?
• Histone modification
–
–
–
Adding and removing of modifying groups to histones by
encymes (methyl, acetyl, ubiquitin or phosphates)
influences on how much DNA is winded around histones
and therefore packed and not transcribable
around 146 base pairs per nucleosome
6
© http://www.krebsinformationsdienst.de/grundlagen/molekularbiologie-grundlagen.php
What is epigenetics?
• RNA interference
–
Micro-RNA (exogenous [Viruses, breast milk] or
endogenous) binds to messenger RNA (RNA induced
silencing complex RISC)
–
–
destroying target RNA
downregulation of genes
© Wikipedia.org
7
Epigenetic effects of human bonding
• Biological impact in humans[11]
–
–
–
–
Short- and long-term effects
Early seperation from mother (orphanages): MRI reduction of white and grey matter,
Amygdala ↑
Interventional studies on preterm infants: stroking and kinesthetic stimulation or kangaroo care:
weight gain↑, alertness ↑, behavioural maturation ↑, better temperature regulation,
growth ↑ in newborns
and
sensitivity and positive affect to infant cues in mothers ↑, breast feeding ↑, maternal rejection
of the newborn ↓
Oxytocin ↑ (lactation, social behaviour, stress responsivity)
[11] Champagne FA: Epigentics of Mammalian Parenting in Narvaez d et al.: “Ancestral Landscapes in Human Evolution: Culture, Childhood and Social Wellbeing”
Oxford Univ. Press, pp.18-37 (2014)
8
Epigenetic effects of human bonding
– orphans: higher DNA methylation in
peripheral blood [12]
– Epigenetic signature after child abuse
DNA-Methylation ↑ in NR3C1-promoterregion in brain (glukocorticoid receptor)
– possible explanation for cross generation
risk of psychological dysfunctions [13]
[12] Naumova OY et al.: Differential patterns of whole-genome DNA methylation in institutionalized children and children raised by their biological parents.
Developmental Psychopathology, 24(1). 143-155 (2012)
[13] McGowan PO et al.: Epigenetic regulation in the glucocorticoid receptor in human brain associates with child abuse. Nature Neuroscience, 12(3), 342-348 (2009)
9
Epigenetic effects of human breastfeeding
• Biological impact of human breast milk [16]:
•
•
•
•
•
•
•
•
Growth ↑
Neurologic development ↑
Gastrointestinal infection ↓
Respiratory tract infections ↓
Otitis media ↓
Necrotizing enterocolitis (NEC)
© http://www.oxbridgebiotech.com
Celiac disease ↓; type-1 diabetes ↓
Later in life: obesity ↓, blood pressure ↓, total and LDL-cholesterol ↓, type-2
diabetes ↓
[16] Verduci E et al.: Epigenetic Effects of Human Breast Milk. Nutrients , 6, pp 1711-1724 (2014)
10
Epigenetic effects of human breastfeeding
• Epigenetically working components of human breast milk
(in vitro / animal studies or hypothetically) [16]
Bestandteil
Klinischer Effekt
Genexpression
Lactoferrin (togehter with
bacteria)
NEC
NF-κB (nuclear factor kappa-light-chain
enhancer of activated B cells) ↓
Otitis media
TNF-α ↓, IL-6 ↓
Prostaglandin J, LCPUFA (long
chain poly unsaturated fatty acids)
PPARγ mRNA (peroxisome proliferatorObesity, non alcoholic fatty liver disease (NAFLD) activated receptor γ) ↑, HMGCoA
reductase ↓
Cholesterol
High blood total cholesterol in adulthood
HMGCoA reductase ↓
undigestible oligosaccharide
Gut dysbiosis ans related alterations (NEC,
infectious diseases, immune system disorders
Different genes (z.B. NF-κB)
–
–
–
–
Breast cancer risk ↓ bei BRCA1
in vitro DHA (Docosahexaenoic acid) PPARβ mRNA ↓ → growth of breast cancer cells ↓
Loads of miRNAs → T-Zell-Regulation, B-Zell-Differenzierung
miRNA transferring inbformation from mother to child after birth[17]
11
[17] Kosaka N et al.: microRNA as a new immune-regulatory agent in breast milk. Silence 1:7 (2010)
Conclusion
– Our phenotype depends on gene expression, which gets regulated by epigenetic
mecanisms:
•
•
•
DNA methylation,
Histone modification,
RNA-Interference
– Our epigenome is changeable and influenced by our environment.
– The earlier the influence on the epigenome the bigger is the impact.
– Bonding and Breastfeeding do have substantial influence on our epigenome:
•
•
•
•
Propably most important factor on stress resistancy later in life
Enhance neurologic maturation
Prevent from infectious diseases
Diminish frequency of metabolic syndrome later in life
12
Thank you very much for you attention!
Sebastian Hentsch
13