.png)
Introduction
The microbiome is an organic ecosystem of trillions of bacteria that live and interact with one another on and within our bodies (Berg et al., 2020). In recent years, more research has been carried out suggesting that the microbiome plays a critical role in our overall well-being, including our gut and skin health (Human Microbiome Project Consortium, 2012). It is widely accepted that every individual’s microbiome is unique, influenced by factors such as sex, age, physical health, lifestyle and environmental factors. However, recent research has emerged which begs the question: is the microbiome influenced by one's genetic makeup or rather by environmental factors? To answer this question, we look at a study conducted on twins to explore how their overlapping and diverse microbial communities give clues about what influences shape our microbiome. Due to limited research on twin skin microbiomes, we will rely on studies conducted predominantly on the gut and some on the oral microbiome.
Defining Twins
To better unearth the relationship between twin microbiomes, it is crucial to understand that not all twins are made alike. Identical twins (monozygotic) share the same DNA sequences, allowing us to better differentiate what elements of the microbiome are linked to genetics and which are influenced by environmental factors. On the other hand, fraternal twins (dizygotic) share about 50% of their DNA. Analysing genetically identical and fraternal twins can allow us to identify the environmental and genetic effects on their microbiome (Martin et al.,1997).
Genetic Influence on Microbial Composition in the Gut
A study (Goodrich et al., 2016) conducted 16S rRNA analysis on the gut microbiomes of approximately 1,126 twins in the United Kingdom. The results showed that the presence of specific genetic variants in the LCT (Lactase) gene locus was associated with relative abundances of the heritable genus Bifidobacterium. It is understood that Bifidobacterium metabolises lactose resulting in individuals exhibiting higher levels of Bifidobacterium if they are unable to produce enough Lactase (Goodrich et al., 2016).
Another study conducted in Missouri, focused on four pairs of female adolescent twins (1 monozygotic and 3 dizygotic pairs). Within each pair, there was significant variability in weights, with one having lower body fat percentages and the other having higher levels. For the purpose of the study, fecal samples were collected from each participant and transplanted into healthy mice. The results of this study showed that the microbiota from the twins with a lower body fat percentage was better at breaking down and fermenting polysaccharides (carbs formed of sugar molecules) than the microbiota of the twins with higher body fat percentages. It was also found that mice who were transplanted with the microbiota of the twins with lower body fat percentage demonstrated protection from obesity phenotype (Ridaura et al, 2013).
Genetic Influence on Microbial Composition in the Oral Cavity
A study published under the name “Longitudinal Study of Oral Microbiome Variation in Twins” in 2020 evaluated the genetic and environmental factors attributed to oral caries (cavities) in both monozygotic and dizygotic twins. Dental plaque samples were extracted and analysed through 16S rRNA. It was noticed that changes in the oral microbiome were strongly influenced by the environment when compared to participant’s genetics. Other elements driving changes in the oral microbiome of twins was their age, the age at which they started brushing their teeth and their actions after brushing.
The study identified the relevance of heritability on the microbiome by way of Capnocytophaga and Actinomyces in monozygotic twins, and Kingella within dizygotic twins. Certain bacteria were more associated with ageing: Veillonella and Corynebacterium. On the other hand, younger subjects were associated with Aggregatibacter. Streptococcus was found to decrease over time and Selenomonas increased with more frequent brushing per day (Freire et al., 2020).
It was reported that unearthing the true biological mechanisms behind caries could unlock the potential to understand biomarkers and pathways that could help with prevention in early ears. However, further research needed to be carried out to reduce this knowledge gap.
Genetic Influence and the Skin Microbiome
Finally, another study conducted in Korea in 2015 evaluated the relationship between genetic and environmental factors on the skin microbiome of twins (Si et al, 2015).
Results from Genetic associations and shared environmental effects on the skin microbiome of Korean twins (Si et al, 2015)
Participants: The study in question included 45 subjects with 16 monozygotic twins, 8 dizygotic twins between the ages of 26 to 55, as well as their mothers and an additional 5 unrelated subjects. In 32 subjects (mothers and twins), skin traits such as pigmentation and skin humidity were measured.
Sample collection: skin swabs were taken from each subject from the upper right arm to reduce variations due to external factors such as different personal care routines and varying cosmetic usage.
Extraction: The entirety of the microbial DNA was extracted from the samples and the V2 and V3 regions of 16S rRNA genes and pyro-sequenced.
Analysis: The 16S rRNA sequencing results were then analysed through Bioinformatics.
Results from Genetic associations and shared environmental effects on the skin microbiome of Korean twins (Si et al, 2015)
The results of this study demonstrated that Propionibacterium (now referred to as Cutibacterium), Staphylococcus and Streptococcus were the richest skin microbiota on a genus level, however as expected there was some variability amongst individuals. It was found that skin pigmentation has a significant impact on the skin bacteria with medium-skinned individuals having an increased microbial diversity. The results also showed that the highest similarities in skin microbiota existed between monozygotic twins followed by dizygotic twins and finally between mothers and twins.
Furthermore, a negative correlation was found with an abundance of C. jeikeium and the allele T, which is a single polymorphism nucleotide (SNP) localised to a gene that plays a significant role in skin barrier function (filaggrin). From past research, we know that defects in filaggrin can be known to result in allergic skin conditions such as ichthyosis vulgaris and atopic eczema, both linked to excessive dryness of the skin (McAleer et al, 2013). This leads us to the conclusion that there might be a link between filaggrin processing and bacteria leading to pathogenesis (when an infection turns into a disease).
To conclude the findings of this study on twin pairs, it was proven that both genetics and environmental factors can shape the skin microbiome (we saw this with pigmentation). A strong correlation between C. jeikeium from the skin microbiota and human genetic factors allele T was also found in relation to skin barrier function (Si et al, 2015).
Next Steps
Further research is needed in order to build on this study conducted in 2015. The question of whether the microbiome is influenced predominantly by genetics or environmental factors plays a crucial role into how we address the skin microbiome and the diseases that have been found to be linked to its disbalance. A significant next step to the work published above would be to include higher resolution taxonomic profiling, quantifying differences at species and strain level between identical twins would be of much importance.
If you are interested in carrying out any research with us in studying the differences between identical twins’ microbiome, or you have questions about our testing platform for your own clinical studies - you can reach us through www.sequential.bio
Lexicon
Dizygotic: fraternal twins who are simply as alike as any other siblings, occurring when two eggs are released at a single ovulation and are fertilised by two different sperm.
Microbiome: The microbiome is a characteristic microbial community occupying a reasonably well-defined habitat which has distinct physio-chemical properties. The microbiome not only refers to the microorganisms involved but also encompasses their theatre of activity, which results in the formation of specific ecological niches. This includes their genetic material, and also structural molecules, like enzymes, membrane lipids or polysaccharides (Definition based on Berg et al., 2020).
Monozygotic: identical twins who develop when one egg is fertilised by a single sperm and then during the first two weeks of conception the developing embryo splits into two, causing two genetically identical babies to develop.
Polysaccharides: Carbs formed of sugar molecules.
Pathogenesis: The process by which an infection deteriorates into a disease.
References
Freire, M., Moustafa, A., Harkins, D.M. et al. Longitudinal Study of Oral Microbiome Variation in Twins. Sci Rep 10, 7954 (2020). https://doi.org/10.1038/s41598-020-64747-1
Martin, N., Boomsma, D. & Machin, G. A twin-pronged attack on complex traits. Nat Genet 17, 387-392, doi:10.1038/ng1297-387 (1997).
Human Microbiome Project Consortium. (2012). Structure, function, and diversity of the healthy human microbiome. Nature, 486(7402), 207-214.
Goodrich, J. K. et al. Genetic Determinants of the Gut Microbiome in UK Twins. Cell Host Microbe 19, 731-743, doi:10.1016/j.chom.2016.04.017 (2016).
Ridaura, V. K. et al. Gut microbiota from twins discordant for obesity modulate metabolism in mice. Science 341, 1241214, doi:10.1126/science.1241214 (2013).
Si, J., Lee, S., Park, J. M., Sung, J. & Ko, G. Genetic associations and shared environmental effects on the skin microbiome of Korean twins. BMC Genomics 16, 992, doi:10.1186/s12864-015-2131-y (2015).
McAleer, M. A. & Irvine, A. D. The multifunctional role of filaggrin in allergic skin disease. J Allergy Clin Immunol 131, 280-291, doi:10.1016/j.jaci.2012.12.668 (2013).