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Talk To Me: How Breastmilk Acts as a Communication and Gene Expression Tool Between Mother and Child

Laurel Wilson, IBCLC, BSc, CLE, CLD, CCCE

www.motherourney.com

info@motherjourney.com

www.facebook.com/laurelwilsonmotherjourney

www.twitter.com/linfinitee

Breastmilk has long been understood to be a pathway towards long-term health for both mother and child. The specific mechanisms for how this communication works has long been studied and today many researchers believe that messenger RNAs and stem cells contribute in many ways to appropriate developmental pathways for the baby and cause gene activation that promotes health for life. mRNA in breastmilk can also be influenced by the time of day and even the timing of the babies delivery, becoming adaptive for the baby’s unique needs. Not only do these messenger RNA communicate important genetic information to the baby via breastmilk, changes in the mothers body via mRNA occur during lactation responding to a new “mothering” focus during the period of lactation. This may impact the mother’s postpartum mental states, adaptation to stress, and changes in fatty acids. This presentation highlights some of the fascinating studies that demonstrate the myriad of ways that stem cells and mRNA during lactation become the ultimate communicators, affecting change for years to come.

Objectives:

A. Identify at least two properties in breastmilk that act as communication tools within the body.

NOTES

B. List one way in which mRNA in breastmilk has a protective effect on the baby.

C. List at least one way mRNA shifts occur in the mother during lactation.

Top Takeaways:

Human milk is both a mechanism and a communication device.

Critical 1000 Days of Influence

Human milk both changes the epigenome of an individual receiving it and the epigenome changes human milk.

NOTES

In addition to In this image you can see that epigenetic impact happens both prenatally and during the period of breastfeeding. The mother is sharing stem cells with the baby resulting in microchimerism. This means that the baby carries these special cells in its body to use during times of stress and illness later in life. The microbes that are being shared with baby seed the microbiome early on. During breastfeeding there is continued influence from the parent. At the top, stem cells continue to be shared with the baby in the milk (more on this later), human milk oligosaccharides are sent in milk to feed bacteria, as well as microbes, cytokines, immunoglobulins and lipids. Essentially milk is a unique, customized genetic cocktail for each and every baby.

Epigenome

· Literally means “above the gene”.

· How our environment influences genetic expression.

· Genome = DNA

· Epigenome = How Phenotypes are Expressed

“Three generations at once are exposed to the same environmental conditions (diet, toxins, hormones, etc.). In order to provide a convincing case for epigenetic inheritance, an epigenetic change must be observed in the 4th generation.”

Only 1-2% of disease comes directly from genetic origin. Our genes do not direct our lives because our genes cannot turn themselves off and on. Only the environment can do that!

If our body were a cellphone

· Genome (Hard Drive)

NOTES

· Epigenome (APPS)

· Phenotype (Program)

Epigenetic Flip Switchers

· Environmental and chemical exposures

· Nutrition

· Emotions, thoughts, beliefs

· Stress

Methylation

Histone Modification

· Deacelylated, condensed genes, difficult to access

· Acetylated, decompressed, easy access to genes

MessengerRNA

· Messenger between DNA and Proteins that express genes through down regulation or translation

Epigenetics at Work

· Food that goes in changes the enzymes in the gut

· Fermentation of proteins of polysaccharides

· Methyls and Acetyl Groups

HMOs

· Can’t be digested by baby

NOTES

· Feed our bacteria

· Genetically driven

· Influenced by geography

HMOs Super Heros of Breastmilk

· Bouncers – bacteria latch on and get a ride out of gut

· Immune Tuners – Dial down immune in gut so bacteria can establish hold

· Feeders –Providing unique nourishment

The Holobiont

40% Human 60% Micro/Mycobiome

Melnik, “There is accumulating evidence that milk functions as a transmitter or relay between the maternal lactation genome and epigenetic regulation of genes of the milk recipient…”

NOTES

Milk transfers lactation specific mRNAs to the baby.

The Exosome

· Membrane Vesicle

· Like the postal service

· Packages items within the cell

· Delivers them to another location

mRNAs can be species specific:

Milk-derived exosomes have been detected in colostrum and mature milk of humans, cows, buffalos, goats, pigs, marsupial tammar wallabies and rodents.

James Edgar, 2016 mRNAs “…provide a means of intercellular communication and of transmission of macromolecules between cells.”

Milk is apparently the most efficient long-distance miRNA transmitter modifying epigenetic regulation of its recipient.

Human milk MRNA uniquely different form Blood mRNA.

mRNA found in Cells, Lipids, and Skim Milk. (Alsaweed, 2015)

Terrific Twos

NOTES

· Influence is strongest

· Inadequacy of immune system to reject genetic material

· Increased plasticity

· Increased vulnerability of epigenome during developmental period

Exosome Activation of Developmental Genes

· Milk exosome/mRNA

· NRFC

· Milk induced translation

· INS

· Insulin expression

· IGF1

· Insulin like growth facctor

· CAV

· Caveolin, May enhance insulin

· FOXP3

· Role in regulatory T cells

Milk Kinship consanguinity?

· High levels of miRNA in breastmilk in first six months of lactation

· Approximately 1.3 × 107 copies/liter/day of miR-181a

· Allows for transfer of genetic material (outside sexual reproduction)

· miRNA’s involved in negative gene regulation

· Single miRNA species can affect expression of many proteins

· Control expression of epigenetic regulators such as affecting methyls and histones

· Rich with mRNAs that promote

· Cellular differentiation and proliferation

· Tissue identity

· Metabolism

· Developmental programming

· Either functional role or a nutritional role.

· Functional - Absorbed by the suckling baby to imply specific actions: for example, to modulate and shape the immune system by regulating T-cells, inducing B-cell differentiation, and preventing the development of allergies

· Nutritional hypothesis suggests miRNAs simply provide nutrition

· miRNAs survive harsh conditions

· Prolonged room temp.

· Acidic conditions

NOTES

· Rnase digestion

· Boiling!!!!

· Pasteurization

Appetite Regulation

“ghrelin mRNA may maintain specific orexigenic and reward signals, whilst ensuring appropriate appetite regulation, a developmental requirement adjusting physiological growth trajectories of the human infant.”

Gut Maturation

It is thus conceivable that milk-derived DNMT-targeting miRNAs support IEC maturation as well as milk stem cell differentiation into enterocytes, potential contributions for appropriate growth, maturation and function of the infant’s gut.

Muscle Mass

Milk-derived exosomal miRNAs provide epigenetic signals for muscle cell differentiation and appropriate muscle protein acquisition.

Without human milk MRNA

· Lack of Human Milk

· Obesity

· Diabetes Type 2

· Cancer

· Neuro-degenerative Diseases

· Alzheimers

· Parkinsons

Alsaweed, 2016

Very few mRNAS in artificial milk are the same as in Human Milk, has low mRNAs in general

Liao, 2017

· miR-22-3p

· Found in ALL mammals

· Help with stem cell differentiations

· Promotes blood flow to heart

· Cell differentiation

· Response to pathogens and autoimmune disease

· miR-30 plus

· Cell differentiation

· miR-148a-3p

· Differentiation of embryonic cells

· Cardiac function

· 20 most abundant mRNAS conc were similar at 2,4,6 months lactation

· Upregulations occurred around 4 months, which may be due to remodeling of breast during weaning (Alsaweed)

· Liao found limited variation of mRNAs from 2-11 months lactation

· Liao and Alsaweed study found 11 of top mRNA were similar (Australia)

· Zhou’s study had similar top 10 mRNAs of Chinese women

· Most abundant mRNAs seems to be present all milk with some change in top abundance

Carney, 2017

· Looked at metabolism mRNAS

· Found 113 were significantly different from at term milk

· 15 with most sig difference seemed to be mRNAs for nitrogen metabolism, biosynthesis, and viral processing

· May be very specific to the preterm baby.

The finding of RNA-containing exosomes in saliva and breast milk, suggests that the shuttling of RNA via exosomes may occur between individuals, during kissing or breastfeeding.

“During breast-feeding, baby saliva reacts with breastmilk to produce reactive oxygen species, while simultaneously providing growth-promoting nucleotide precursors. Milk thus plays more than a simply nutritional role in mammals, interacting with infant saliva to produce a potent combination of stimulatory and inhibitory metabolites that regulate early oral–and hence gut–microbiota. Consequently, milk-saliva mixing appears to represent unique biochemical synergism which boosts early innate immunity.” Al-Sheheri, 2015

NOTES

Breastfeeding changes mRNAs in maternal brain, as well

Human Milk

· Bonding

· Milk Supply

· Mental Health

· Maternal Behavior

· Immune System

· Growth Patterns

· Organ Development

· Gut maturation

Questions:

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References:

Talk To Me Bibliography

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