Simona Cristea Profile picture
Dec 27 22 tweets 7 min read
We all know that babies inherit their microbiome from mum👩‍👧(vertical gene transfer).

First time ever, a brand new🔥study finds another novel mechanism for microbiome sharing between mothers & their infants: horizontal gene 🧬 transfer.

Why is this totally crazy?

Let's unpack🧵 Image
Let's first clarify why these findings might seem shocking:

This paper found hundreds of mother-to-infant gene bacterial transmission events WITHOUT transmission of the full bacterial genomes themselves.

This is called horizontal gene transfer.

cell.com/cell/fulltext/…
This paper, a #multiomics longitudinal study just out in @CellCellPress, tracked the co-development of microbiomes & metabolomes from late pregnancy to 1 year of age in 70 mother-infant pairs.

Top 5 main findings, explained👇 Image
1. Infant microbiome and metabolome are distinct from maternal and influenced by diet.

Delivery mode, breastfeeding, use and type of infant formula, and prior antibiotics significantly influence the infant microbiome and metabolome. Image
2. Maternal metabolic health is impacted by microbiome and metabolome shifts during pregnancy.

Analysis of paired stool samples from 31 mothers at delivery & 3 months postpartum found altered metabolites, such as expansion of steroid metabolites at delivery. Image
Interestingly, many of these compounds were associated with impaired glucose tolerance during pregnancy.

For example, pregnancy was characterized by higher abundance of Methanobrevibacter smithii, a common microorganism linked to obesity, impaired glucose tolerance & diabetes.
3. Maternal species influence the infant microbiome through mobile genetic elements ‼️

We already know that some of the strains in the infant gut originate from the maternal gut and are transmitted at, or soon after, birth.

But does transmission also occur later on, in infancy?
The paper analyzed SNP haplotypes of the dominant strain of each identified microbiome species to find the identical strains between mother & infant.

Then it looked for situations when these strains first appear later on in the infant’s life.

Many such instances were found 😳
This hints to the hypothesis that maternal species influence the infant gut microbiome by also contributing genes through horizontal gene transfer.

Horizontal gene transfer means transfer that hasn’t happened via direct inheritance from mother to infant, rather via other ways.
To rigorously test this, the authors curated maternal metagenomes for metagenome-assembled genomes (MAG) & filtered them to species not observed in the corresponding babies

Then they screened the babies metagenomic assemblies for 100% nucleotide match to genes from maternal MAGs Image
This approach revealed 977 unique genes shared across 22 mother-infant pairs, spanning 11 maternal bacterial species (significant increase over baseline gene-sharing events between unrelated mothers and infants). Image
Functional annotation of these genes showed enrichment of transduction, transposons and conjugation, hinting to the mechanisms by which this horizontal gene transfer occurs. Image
Interestingly, the analysis also identified a high-quality prophage segment on a maternal MAG, also present in 2 MAGs from the corresponding infant at 3 & 6 months

So phages may mediate mum-to-baby horizontal gene transfer between bacterial strains without vertical transfer. Image
4. Infants develop their own unique gut metabolic environment, influenced by the microbiome.

Infant gut metabolomes consistently displayed less diversity than mothers’, with 70,000 observed metabolomic features compared to nearly 90,000 in mothers. Image
5. Breastfeeding influences the infant gut metagenome & metabolome, likely contributing to immune maturation.

Markers of intestinal & systemic inflammation positively correlated in 1 yr & negatively in young infants.

This may be immune maturation facilitated by breastfeeding. Image
Let’s recap!

This study asked:

How do the microbiomes of mother & baby change and influence eachother during pregnancy and first year of life?

What it found:

Some bacteria in mother’s gut donate hundreds of genes to bacteria in baby’s gut as ongoing transmission after birth.
The fact that this transmission continues after birth, and up to 1 year of life, was previously unknown.

The transferred genes are beneficial to the baby’s gut.

They have immune & neurological functions, as well as involvement in dietary adaptation (start solids) as babies grow
This transfer mode, where maternal gut bacterial strains share genes with infant gut strains in the absence of persistent transmission of the bacterial genomes themselves, is horizontal gene transfer.

It is a first that horizontal gene transfer is documented from mother to baby.
The authors speculate that one possible mechanism by which horizontal gene transfer happens is that the distinct environment of the infant gut triggers prophage (viruses that reside on bacterial genomes) induction in vertically transmitted strains that are unable to engraft.
Food for thought:

Are mothers the only ones from whom babies get parts of microbiome after birth? How about family members? Daycare friends?

We don’t yet know, but I’m already excited about future works!

Kudos 👏🏼 to @TheXavierLab @broadinstitute for such an insightful study!
Wrapping it up:

Great thread to end the year!

Mums, congratulate yourself once again for the wonderful job you are doing 🥰👩‍👧👩‍👦 #WomenInSTEM #motherhood

Science amazes us every day, there are so many reasons to be in awe!

Share this story and make more people amazed!
congrats👏🏼👏🏼 first author @tvatanen @helsinkiuni for this work and for shedding some light on such complex mechanisms!

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Dec 9
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The genomics single cell field has started out 1-2 decades ago with a huge promise:

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Let’s unpack the details & relevance of this study👇🧵
First things first:

Here’s the link to the paper, which has been made public by @Nature in an unedited form (before official publication), due to its perceived immediate relevance to the research & clinical cancer communities.

nature.com/articles/s4158…
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