633
J. Cosmet. Sci., 75.6, 633–659 (November/December 2024)
*Address all correspondence to Annabelle Schaefer, annabelle@sequential.bio
The Bidirectional Gut-Skin Axis: Emerging Evidence and
Potential Skin Health Implications
ANNABELLE SCHAEFER, AYANNA LUTHRA, MATHILDE TARDIF, ALBERT DASHI
AND OLIVER WORSLEY
Sequential Skin Ltd, 85 Great Portland Street, London, UK (A.S., A.L, M.T., A.D., O.W.)
Accepted for publication on October 1, 2024.
Synopsis
This review article explores the emerging field of the gut-skin axis, examining how the gut microbiome
influences skin health, particularly in conditions such as acne, atopic dermatitis and rosacea. We investigate
the mechanisms of communication between the gut microbiome and the skin in these conditions, among
others, as well as the current therapeutic and cosmetic applications targeting these interactions. Additionally,
we introduce the novel concept of the skin-gut axis, which describes how skin injury can impact the gut
microbiome and potentially affect systemic health. This innovative area of study unveils new opportunities
for systemic treatments that address both skin and gut health, presenting promising strategies for holistic
management of dermatological disorders and potentially overall health.
INTRODUCTION
THE GUT AND SKIN MICROBIOMES
In recent decades, research has increasingly illuminated the role of the microbiome in
modulating human health. The term “microbiome” refers to the genetic material of the
intricate community of microorganisms—bacteria, fungi, archaea, viruses and protozoa—
that colonize various surfaces of the human body and interact in complex ways.1 Notably,
skin and gut microbiomes have emerged as prominent fields of investigation in the context
of human health. The skin microbiome, for instance, plays critical roles in immune defense,
maintaining barrier function and influencing skin homeostasis.2 It helps prevent pathogen
colonization, contributes to skin hydration and participates in the synthesis of certain
vitamins.2 Similarly, the gut microbiome is vital for digestion regulation, the processing
of nutrients and metabolites, as well as immune system support through the prevention of
pathogenic invasion.1 Both external factors, such as environmental exposures (for example,
ultraviolet radiation (UV) and pollution for the skin microbiome, and diet and oral
medication for the gut microbiome), and internal factors, including genetic predispositions
and host immune responses, profoundly influence the composition and dynamics of the

634 JOURNAL OF COSMETIC SCIENCE
microbiome.2 Understanding these interactions is crucial for deciphering their impact on
health and disease, paving the way for targeted interventions and therapies that harness the
microbiome’s potential to support overall well-being.
Furthermore, the interactions between the gut microbiome and the skin, commonly referred
to as the “gut-skin axis,” have been increasingly clarified. Research has firmly established
that the gut-skin axis represents a pathway of communication between the gastrointestinal
(GI) tract and the skin, highlighting the interconnectedness of these two organ systems.3
While the terms “skin-gut axis” and “gut-skin axis” are often used interchangeably in
research, this review will specifically use “gut-skin axis” to denote the communication
pathway from the gut microbiome to the skin. The mechanisms underlying this link
from the gut microbiome to the skin include immunomodulation, wherein the gut
microbiome influences the systemic immune response, impacting skin inflammation and
immune function.4 Hormonal pathways also play a crucial role, as hormones produced in
response to gut microbial activity can affect skin physiology.3 Additionally, the production
of metabolites, such as short-chain fatty acids (SCFAs) by gut bacteria, can enter the
bloodstream and exert effects on skin cells, contributing to the regulation of skin barrier
function and inflammatory processes.5 Interestingly, emerging research has postulated the
bidirectional nature of this axis, suggesting that the state of the skin may, in turn, influence
the gut microbiome, known in this review as the “skin-gut axis.”6
Historically, microbiome studies primarily relied on culture-based techniques to identify
microorganisms present in samples.2Whilevaluableatthetime,thesemethodshadsignificant
limitations, including an inability to accurately represent the endogenous microbiome
environment and difficulties in culturing many microorganisms.7 Therefore, the introduction
of DNA-based culture-independent molecular techniques in the 1980s revolutionized
microbiome research.7 This paradigm shift involving analyzing the microbial DNA directly
from samples, instead of DNA from lab-grown cultures, redirected researchers’ focus toward
understanding microbial functions and interactions. Hence, metagenomics, which refers to
the study of the genetic material of entire communities of organisms, has emerged as a
pivotal technique.7 Ultimately, the “multi-omics” approach—comprising metagenomics and
additionally, metatranscriptomics, proteomics, lipidomics, and metabolomics—has become
standard practice for microbiome studies and these comprehensive methodologies are crucial
for advancing the understanding of the microbiome (summarized in Table I).
THE MULTI-OMICS APPROACH
Metagenomics is the unbiased study of the sequences and functions of all genetic information
extracted from a specific environment, such as the human skin microbiome. By employing
diverse bioinformatic systems and genomic technologies, metagenomics enables researchers
to explore the entire genome of various environmental communities and gives insight into
the diversity, structure and functional potential thereof.8 This approach was first introduced
in 1998 in reference to shotgun metagenomic sequencing. Nowadays, it is largely applied
to studies of marker genes, such as the 16S ribosomal RNA (rRNA) gene in the form
of targeted bacterial profiling (summarized in Table II).9,10 This method of microbiome
sequencing targets the 16S rRNA gene, which is highly conserved among bacteria and
archaea, although it contains hypervariable regions that can distinguish between different
species.11 Similarly, internal transcribed spacer (ITS) region amplification focuses on the
ITS region of the rRNA gene cluster, which is highly variable among different fungal