636 JOURNAL OF COSMETIC SCIENCE
Furthermore, proteomics complements these other “omics” fields as a means to analyze
gene activity, the levels of proteins secreted from host cells and the post-translational
modifications thereof.1 Metaproteomics, a specialized branch of proteomics, plays a crucial
role in characterizing microbiome systems and elucidating the factors that mediate
molecular interactions between the host and microbiota.16 For instance, proteomics identifies
microbial proteins linked to dysbiosis and various GI and metabolic disorders. It also aids
Table I
Different Multi-omic Approaches Used for Microbiome Research
Multi-omics Purpose Molecular technique(s)
Metagenomics Study of the sequences and functions of all genetic
information extracted from a specific site
Shotgun sequencing19
16S rRNA gene sequencing19
ITS region sequencing19
Long-read sequencing20
Transcriptomics Analysis of the transcriptome, a collection of all
the RNA in a cell, tissue or organ
RNA sequencing1
NGS21
Metabolomics Analysis of small molecules, known as metabolites,
intermediates, products of cell metabolism in
cell, tissues, biofluids or organisms
Nuclear magnetic resonance
(NMR)22
Mass spectrometry (MS)22
Proteomics Study of proteins, and their functions, structures
and interactions within a biological system
Gel electrophoresis17
Protein microarrays17
MS17
Lipidomics Study of lipids, and their functions, structures and
interactions within a biological system
MS23
NMR24
Gas chromatography (GC)24
Table II
Comparison of Different Molecular Techniques Used to Sequence the Genetic Material of Microbes
Within the Microbiome
Method Description Main advantage(s) Main disadvantage(s)
16S gene
sequencing
Sequ­­encing targeting the
16S rRNA gene
Cost-effective for
bacterial identification
Limited to genus-level
identification due to
similarities between
closely related species
Enables classification
into taxonomic groups
Provides no information on
the functional capabilities
of the microbes
ITS gene
sequencing
Amplification of the ITS
region of
Allows identification of
different fungal
species
Can only detect fungi at the
species level
Shotgun
sequencing
Fragmentation of total
DNA, followed by library
preparation and
sequencing using
bioinformatic tools
Provides predictive
functional analysis for
bacteria, fungi and the
host
Requires high
computational power and
complex analytical tools
Long-read
sequencing
Sequencing of DNA without
the need to fragment it
into smaller pieces
Reads longer sequences,
enabling cost-effective
strain-level analysis
Higher error rates compared
to other sequencing
methods
qPCR Amplification and
quantification of target
DNA/RNA
Rapid quantification of
sequences
Dependent on a standard
curve for accuracy
Can detect low
concentrations of
nucleic acids
Susceptible to inhibition by
contaminants

637 Bidirectional Gut-Skin Axis
in understanding how these microbial proteins affect host physiological processes and
immune responses. As a result, proteomics provides essential insights into the functional
roles of microbiome-derived proteins and their impact on host health, complementing
the insights gained from metagenomics and metatranscriptomics. Gel electrophoresis,
protein microarrays and MS are all examples of molecular techniques used to investigate
microbiome proteomics.17
Lastly, lipidomics utilizes analytical chemistry tools and principles to study lipid
structures, molecular species abundance, cell functions and, subsequently, microbial-host
interactions.18 This is possible through the identification and quantification of changes in
lipid signaling, metabolism, trafficking and balance within cells.18 MS, NMR and GC are
all approaches used to explore lipidomics in microbiome studies. When used in conjunction,
these multi-omic approaches provide a comprehensive view of microbiome communities,
including both their composition and the functional roles of individual taxa or groups of
taxa within. Integrating this data enables researchers to gain insight into the dynamics of
entire ecosystems, microbial-host interactions and, overall, supports the formulation and
validation of specific hypotheses, aiming for more robust conclusions.8
THE ESTABLISHED ROLE OF THE GUT-SKIN AXIS IN SKIN CONDITIONS
Research has increasingly demonstrated an association between the gut microbiome and
the skin, elucidating the communication pathway known as the gut-skin axis (Figure 1).
The gut microbiome plays a vital role in the regulation of the immune system by protecting
against exogenous pathogens and priming immunoprotective responses. Therefore, it is
responsible for maintaining homeostasis through communication with multiple tissues and
organs, like the skin.25 Consequently, abnormal levels of commensal bacteria in the gut
microbiome may lead to intestinal dysbiosis, which is associated with an altered immune
response and the pathophysiology of multiple inflammatory diseases, related to the gut and
skin, potentially disrupting cutaneous homeostasis.26
The specific mechanisms of communication between the gut microbiome and the skin involve
the immune system and the neuroendocrine system.25 Beginning with diet, part of the healthy
functioning of the gut microbiome includes the degradation of complex polysaccharides into
metabolites, vitamins and SCFAs, the latter of which directly contribute to maintaining the
integrity of the epithelial barrier.27 Conversely, intestinal dysbiosis—which may be caused by
a multitude of factors—is likely to trigger T lymphocyte (T cell) activation and the disruption
of immunosuppressive cytokines and regulatory T lymphocyte (Treg) cells that function to
maintain microbial homeostasis, thereby increasing systemic inflammation.28,29 Oftentimes,
this causes increased intestinal permeability. The disruption of this epithelial barrier may
allow gut microbes, toxins and other metabolites to enter the bloodstream, further triggering
elevated inflammatory cytokine production and T cell responses locally, systemically, and
in the skin.27 In the skin, this may lead to decreased keratin synthesis, altered epidermal
differentiation and, ultimately, the weakening of the skin barrier.28–30
Therefore, microbial metabolites may influence the gut-skin axis by interacting with skin
receptors, potentially affecting the cutaneous environment.3 The most extensively studied
microbial metabolites are SCFAs, which are aliphatic carboxylic acids with fewer than six
carbon atoms, including butyrate, acetate and propionate.31 These are produced by the
fermentation of undigested polysaccharides by intestinal microbes in the colon, primarily