Predictors of the Microbiome

Why the Microbiome Matters

• Novel research continues to examine the role of the microbiome in disease states
• Better understanding of the relationship among biological sex, genetics, and cohabitation on the microbiome can provide a new perspective on the role of these factors in disease

A microbiome is defined as the microorganisms of a particular environment, often describing the community of bacteria that live inside or on the human body – such as in the nose, throat, mouth, vagina, intestines, or on the skin. Microbial communities impact host energy metabolism and immunity, contributing to maintenance of health or initiation of disease.

Prebiotic and probiotic consumption may allow for manipulation of the microbiome.¹ Lactobacillus and Bifidobacterium are the most commonly investigated probiotics, although many bacterial species and strains are being analyzed for clinical benefit in a wide variety of conditions, from diarrhea to acne vulgaris.

Interestingly, however, the microbiome composition varies greatly from person to person. Whereas human genomes are about 99.9% identical to one another, hand and gut microbiomes can differ by 80%-90%.² This article will explore factors that influence the composition of our individual gut and skin microbiomes.

Biological Sex and the Microbiome

Numerous factors that may modulate differences in gut microbiota have been identified and often include but are not limited to:

• Sex hormones and microbiota interaction
• Differential drug and antibiotic use between males and females
• Diet
• Body mass index
• Colonic transit time³

Sex differences in the gut microbiota have been observed mainly in animal studies, with mice studies showing that genetic background is a stronger determinant of intestinal microbiota than sex difference.³ Several human studies have analyzed sex differences in gut microbiota with mixed results.³ One study analyzed the influence of sex, handedness, and washing on the diversity of hand surface bacteria and found a significantly higher bacterial diversity in women and significant differences in bacterial communities between men and women (p < 0.001).⁴ There was:

• 37% more abundance of Propionibacterium on men
• 80% more abundance of Corynebacterium on men
• 400% more abundance of Enterobacteriales on women
• 180% more abundance of Moraxellaceae on women
• 340% more abundance of Lactobacillaceae on women
• 180% more abundance of Psuedomonadaceae on women⁴

In another study, microbial analysis of airborne dust collected from dormitory rooms found differences in bacterial communities based on the sex of the occupants. The researchers found that taxa of the vaginal microbiome were more common in female-occupied rooms, whereas taxa associated with male urogenital microbiota or human skin were more common in male-occupied rooms. Compositional differences were so consistent that analysis of the abundances of bacterial genera allowed the researchers to predict the sex of room occupants with 79% accuracy.⁵

Ultimately, these studies demonstrate biological sex to be a predictor of microbiome diversity and composition. However, the influence of confounding factors that characteristically differ between men and women increases the difficulty of analyzing the effect of biological sex alone. 

Host Genetics and the Microbiome

As previously described, mouse studies showed that genetic diversity appears to be a greater predictor of the microbiome than sex differences.³ However, human studies have had variable and inconsistent results, likely owing to microbiome complexity, confounding variables and multiple comparisons, and the large affect of the environment.⁶ Still, twin and mouse studies have been instrumental in uncovering the relationship between the host genome and the microbiome. 

Early twin studies found no significant difference in the gut microbiome composition between monozygotic and dizygotic twins, although the number of twin pairs in these studies was relatively small (under 100 twin pairs). Studies with larger sample sizes (400+ twin pairs) found the host genome to be associated with abundances of specific members of the intestinal microbiota.⁶ These studies identified the family Christensenellaceae (phylum Firmicutes) to be the most heritable, and a follow-up study demonstrated that heritable taxa are temporally stable over long periods of time.

Interestingly, however, a study of 250 twins in the UK demonstrated that the microbial similarity between twins declined as they began to live apart, indicating that in addition to genetics, the environment may also influence the microbiome.⁶

In addition, several non-twin studies showed bacterial similarity among unrelated individuals cohabitating, whereas bacterial similarity was not observed among family members living in separate households. These results indicate that cohabitating had a greater influence on the microbiome than relatedness. 

Cohabitation and the Microbiome

Additional studies have examined cohabitation and the microbiome. A 2017 study sought to determine if cohabitation led to shared skin microbiota by comparing samples of microbial communities from seventeen skin sites of ten sexually active cohabiting couples. The researchers found that cohabitation was significantly associated with microbial community composition, although certain factors reduced this association on specific body locations.⁷

The most similar skin microbiome was found on the couples’ feet, whereas thigh microbial communities were more strongly associated with biological sex.⁷ Skin care products, pet ownership, allergies, and alcohol consumption also impacted the skin microbiome of specific locations of the body.⁷

Despite these site-specific differences, partners could be predicted 86% of the time (p < 0.001) based on their skin microbiome profiles.⁷

Another study examined the influence of cohabitation on fecal, oral, and skin microbiota, in addition to how dog ownership impacts this relationship. Surveys of the fecal, oral, and skin microbiota of 159 individuals from 60 families demonstrated that microbiome communities were more similar among families than between them at every site.⁸ However, this pattern was strongest for the skin microbiome.

Interestingly, the researchers found that dog-ownership significantly increased the degree of skin microbiota similarity among cohabiting adults. Furthermore, adults shared more skin microbiota with their own dogs than with other dogs.⁸

Despite these interesting findings, the mechanism of shared skin, fecal, and oral microbiota among cohabitating couples and siblings is not fully understood. Furthermore, the stability of this association over time is unknown.⁸

Summative Effect of Genetic Similarity and Cohabitation

To analyze the combined influence of genetic similarity and cohabitation on the microbiome, a 2019 study analyzed the similarity in the gut microbiome among cohabitating monozygotic (MZ) twins, non-cohabitating MZ twins, spouse pairs, and non-related pairs.⁹ They utilized the Bray-Curtis (BC) dissimilarity metric, an index measure of beta diversity bounded between zero and one, with:

• Zero meaning the two comparison groups have the same composition of microbiota
• One meaning the two comparison groups do not have the same composition of microbiota

As anticipated, they found that cohabitating MZ twin pairs had the most similar gut microbiota when compared to all other pair types (non-cohabitating MZ twins, spouses, and unrelated pairs). Interestingly, however, they also found a significant difference between BC measures from cohabitating spouse pairs and BC measures from unrelated individuals (p-value < 0.00001), with unrelated, yet cohabiting spouse pairs exhibiting greater shared microbiota.⁹

Summary

Antibiotic use and diet are known to influence the diversity and composition of the microbiome. Studies have found that biological sex, the host genome, and cohabitation influence the host microbiome although study designs differ removal of confounding variables is impossible. Understanding the role of these factors on the composition and diversity of the microbiome may improve our knowledge of how our microbiome maintains our health or contributes to the development of disease.