Catherine O'Neill

The University of Manchester · Centre for Dermatology

Aims The aryl hydrocarbon receptor (AhR) is a ligand-activated receptor implicated in many inflammatory disorders. The skin microbiota plays a crucial role in maintaining epidermal barrier integrity and is thought to modulate skin homeostasis partly through the production of AhR ligands, including metabolites of microbial tryptophan metabolism such...

As our understanding of dermatological conditions advances, it becomes increasingly evident that traditional pharmaceutical interventions are not universally effective. The intricate balance of the skin microbiota plays a pivotal role in the development of various skin conditions, prompting a growing interest in probiotics, or live biotherapeutic p...

We have evaluated the inhibitory effects of supernatants and lysates derived from several candidate probiotics, on the growth and biofilm formation of wound pathogens, and their ability to protect human primary epidermal keratinocytes from the toxic effects of pathogens. Supernatants (neutralized and non-neutralized) and lysates (via sonication) fr...

The therapeutic application of blue light (380 – 500nm) has garnered considerable attention in recent years as it offers a non-invasive approach for the management of prevalent skin conditions including acne vulgaris and atopic dermatitis. These conditions are often characterised by an imbalance in the microbial communities that colonise our skin,...

The therapeutic application of blue light (380 – 500nm) has garnered considerable attention in recent years as it offers a non-invasive approach for the management of prevalent skin conditions including acne vulgaris and atopic dermatitis. These conditions are often characterised by an imbalance in the microbial communities that colonise our skin,...

Recent studies have provided strong evidence of a functional link between the microbiota of the skin and overall host health. While sunscreens offer protection against acute and chronic dermatological damage by reflecting, absorbing and scattering ultraviolet radiation, their impact on the skin microbiota is poorly understood. The use of sunscreens...

Objectives There is growing recognition that interactions between bacteria and the immune response may contribute to inflammation in psoriatic arthritis (PsA). To identify how the skin and stool microbiota may contribute to pathogenesis, we analysed the microbiota and immunophenotype of patients with PsA before and after therapy. Methods We examine...

Skin Commensal Bacteria Modulate Ultraviolet Radiation-Induced Cytokine Secretion in Human Keratinocytes. Hannah J. Serrage a, Mark D. Farrar a, Andrew J. McBain b, Joanne Pennock a, Chunting Deng a, Catherine O’Neill a,c a School of Biological Sciences, FBMH, The University of Manchester, UK bSchool of Health Sciences, FBMH, The University of Ma...

In the quest for mitigators of bacterial virulence, cell-free supernatants (CFS) from 25 human commensal and associated bacteria were tested for activity against Pseudomonas aeruginosa. Among these, Escherichia coli Nissle 1917 CFS significantly inhibited biofilm formation and dispersed extant pseudomonas biofilms without inhibiting planktonic bact...

An understanding of the timescales of commensal skin microbiota reestablishment following perturbation is required to inform consumer safety risk assessment and support product development. Following ethanol exposure, total bacterial populations and microbiome diversity recovered after 6 h.

We have previously shown that lysates of Lacticaseibacillus rhamnosus GG confer protection to human keratinocytes against Staphylococcus aureus. L. rhamnosus GG inhibits the growth of S. aureus as well as competitively excludes and displaces the pathogen from keratinocytes. In this study, we have specifically investigated the anti-adhesive action....

Dandruff is a common scalp condition, which frequently causes psychological distress in those affected. Dandruff is considered to be caused by an interplay of several factors. However, the pathogenesis of dandruff remains under‐investigated, especially with respect to the contribution of the hair follicle. As the hair follicle exhibits unique immun...

Inflammation is a vital defence mechanism used to protect the body from invading pathogens, but dysregulation can lead to chronic inflammatory disorders such as psoriasis and atopic dermatitis. Differences in microbiota composition have been observed in patients with inflammatory skin conditions compared with healthy individuals, particularly withi...

Beneficial bacteria represent an emerging tool against topical diseases, including infection caused by Staphylococcus aureus. Here, we investigated several anti-pathogenic mechanisms of the model probiotic Lacticaseibacillus rhamnosus GG against a clinical S. aureus isolate by implementing various mutants lacking important cell surface molecules. W...

Background: Staphylococcus aureus is the dominant infective trigger of atopic dermatitis (AD). How this bacterium drives type 2 allergic pathology in the absence of infection in patients with AD is unclear. Objective: We sought to identify the S aureus–derived virulence factor(s) that initiates the cutaneous type 2–promoting immune response respons...

The larvae of the wax moth Galleria mellonella and human oral keratinocytes were used to investigate the protective activity of the candidate oral probiotics Lactobacillus rhamnosus GG (LHR), Lactobacillus reuteri (LR), and Streptococcus salivarius K-12 (SS) against the periodontal pathogens Fusobacterium nucleatum (FN), Porphyromonas gingivalis (P...

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Background The epidermal barrier is important for water conservation, failure of which is evident in dry skin conditions. Barrier function is fulfilled by the stratum corneum, tight junctions (TJs; which control extracellular water) and keratinocyte mechanisms, such as organic osmolyte transport, which regulate intracellular water homeostasis. Orga...

Aging is characterized by the deterioration of tissue structure and function. In skin, environmental factors, for example, ultraviolet radiation (UVR), can accelerate the effects of aging such as decline in barrier function and subsequent loss of hydration. Water homeostasis is vital for all cellular functions and it is known that organic osmolyte...

Staphylococcus aureus causes the majority of skin and soft tissue infections. Half of patients treated for primary skin infections suffer recurrences within 6 months despite appropriate antibiotic sensitivities and infection control measures. We investigated whether S. aureus internalized by human skin keratinocytes are effectively eradicated by st...

Microbiomes associated with human skin and the oral cavity are uniquely exposed to personal care regimes. Changes in the composition and activities of the microbial communities in these environments can be utilized to promote consumer health benefits, for example, by reducing the numbers, composition, or activities of microbes implicated in conditi...

Human skin forms the main barrier between the internal system and the external environment. This barrier is crucial in two ways. First, it protects the internal system from external insults such as ultraviolet radiation and toxins. Second, it prevents excessive water loss and maintains water and electrolytes homeostasis. Tight junctions of the epid...

Epidermal barrier function is provided by the highly keratinised stratum corneum and also by tight junctions (TJs) in the granular layer of skin. The development of the TJ barrier significantly deteriorates in response to ultraviolet B radiation (UVB). Following exposure to UVB, keratinocytes accumulate organic osmolytes, which are known to preserv...

A competent epidermal barrier is crucial for terrestrial mammals. This barrier must keep in water and prevent entry of noxious stimuli. Most importantly, the epidermis must also be a barrier to ultraviolet radiation (UVR) from the sunlight. Currently, the effects of ultraviolet radiation on epidermal barrier function are poorly understood. However,...

The realisation that microbes regarded as beneficial to the host can impart effects at sites distant from their habitat, has raised many possibilities for treatment of diseases. The objective of a workshop hosted in Turku, Finland, by the International Scientific Association for Probiotics and Prebiotics, was to assess the evidence for these effect...

In recent years the application of high throughput DNA sequencing for analyzing the composition of the skin microbiota has identified a highly diverse group of microorganisms. Although the factors determining the composition of the skin microbiota are not completely understood, it is clear that an array of bacteria including Staphylococcus epidermi...

As crucial interface organs gut and skin have much in common. Therefore it is unsurprising that several gut pathologies have skin co-morbidities. Nevertheless, the reason for this remains ill explored, and neither mainstream gastroenterology nor dermatology research have systematically investigated the ‘gut-skin axis'. Here, in reviewing the field,...

A limited number of studies have investigated the potential of probiotics to promote wound healing in the digestive tract. The aim of the current investigation was to determine whether probiotic bacteria or their extracts could be beneficial in cutaneous wound healing. A keratinocyte monolayer scratch assay was used to assess re-epithelialization;...

BackgroundATP-binding cassette (ABC) transporters are involved in the active transport of an extremely diverse range of substrates across biological membranes. These transporters are commonly implicated in the development of multidrug resistance and are also involved in numerous physiological and homeostatic processes, including lipid transport, ce...

As studies uncover the breadth of microbes associated with human life, opportunities will emerge to manipulate and augment their functions in ways that improve health and longevity. From involvement in the complexities of reproduction and fetal/infant development, to delaying the onset of disease, and indeed countering many maladies, microbes offer...

Few studies have evaluated the potential benefits of the topical application of probiotic bacteria or material derived from them. We have investigated whether a probiotic bacterium, Lactobacillus rhamnosus GG, can inhibit Staphylococcus aureus infection of human primary keratinocytes in culture. When primary human keratinocytes were exposed to S. a...

The ability to conserve water is fundamental to terrestrial life. A number of organs such as the kidney and the bladder have important roles in the regulation of body water balance. The epidermis of skin is also fundamental to this process and it is in a constant battle to prevent loss of water to the external, dry environment. Given this important...

In this study, we investigated whether probiotic lysates can modify the tight-junction function of human primary keratinocytes. The keratinocytes were grown on cell culture inserts and treated with lysates from Bifidobacterium longum, Lactobacillus plantarum, Lactobacillus reuteri, Lactobacillus fermentum, or Lactobacillus rhamnosus GG. With the ex...

Epidermal barrier acquisition during late murine gestation is accompanied by an increase in Akt kinase activity and cJun dephosphorlyation. The latter is directed by the Ppp2r2a regulatory subunit of the Pp2a phosphatase. This was accompanied by a change of Claudin-1 localisation to the cell surface and interaction between Occludin and Claudin-1 wh...

Introduction: Tight junctions are intercellular permeability seals that regulate paracellular transport across epithelia. Tight junction function, expression and localisation of constituent proteins are significantly altered by cytokines such as TNFα. Glucagon-like peptide-2 (GLP-2) is an intestinotrophic enteroendocrine peptide. It is not known w...

Recent studies have suggested that the topical application of probiotic bacteria can improve skin health or combat disease. We have utilized a primary human keratinocyte culture model to investigate whether probiotic bacteria can inhibit Staphylococcus aureus infection. Evaluation of the candidate probiotics Lactobacillus reuteri ATCC 55730, Lactob...

Dipeptidyl peptidase 4 (DP4) is a serine protease that preferentially cleaves N-terminal dipeptides from polypeptides containing proline or alanine as the penultimate amino acid. DP4 inactivates glucagon like peptide-2 (GLP-2), a trophic peptide with cytoprotective and reparative properties in the injured gut; therefore DP4 potentially inhibits rep...

Introduction Dipeptidyl peptidase IV (DP IV) is a serine protease. It modulates the physiological activity of satiety inducing hormones such as glucagon like peptide 1 (GLP-1) and polypeptide YY (PYY). It also inactivates GLP-2, an enteroendocrine hormone with cytoprotective and reparative properties. By cleaving chemokines essential for the Th-2 i...

Epithelia are found at the interfaces between body compartments where they act as selective permeability barriers that maintain the unique composition of the compartments on either side. Epithelial barrier function is dependent on tight junctions (TJs), which seal the intercellular or paracellular spaces but may permit selective permeability. In si...

Variants in the interleukin-23 receptor (IL23R) and the autophagy-related 16-like 1 (ATG16L1) genes have been associated with an increased risk of Crohn's disease (CD). Both genes were identified through genome-wide association scans and subsequent studies have validated these associations. To assess the effect size of these variants, an independen...

The mycotoxin patulin is a common contaminant of fruit. Here, we demonstrate that patulin reduces the barrier properties of the intestinal cell line, caco-2 by specific effects on tight junction components. Within 5h of exposure to 100 microM toxin, the transepithelial electrical resistance of caco-2 monolayers was reduced by approximately 95% and...

We investigated the influence of docosahexaenoic acid (DHA) on the fatty acid and protein compositions of two populations of membrane rafts present in Caco-2 cells. DHA (100 microM) had no significant influence on the fatty acid or protein compositions of tight junction-associated, Lubrol insoluble, membrane rafts. However, DHA did significantly al...

Epithelial tight junctions play a central role in cell-cell adhesion and are necessary for the selective paracellular movement of ions. Claudins are key components of tight junctions and their expression is altered in gut epithelia in a variety of inflammatory enteropathies, including ulcerative colitis and Crohn's disease. Psoriasis is a chronic i...

Ochratoxin A (OchA) is a food-borne mycotoxin with multiple effects in vivo. Previously, we have demonstrated that the toxin can significantly impair the barrier function of the gut epithelial cell line, Caco-2. Barrier disruption involved loss of claudins 3 and 4, but not claudin 1 from the tight junction complex. In this study, we demonstrate for...

In a previous study we demonstrated that depletion of Caco-2 cell cholesterol results in the loss of tight junction (TJ) integrity through the movement of claudins 3 and 4 and occludin, but not claudin 1, out of the TJs [1]. The aims of this study were to determine whether the major tight junction (TJ) proteins in Caco-2 cells are associated with c...

Several hundred species of bacteria inhabit the gut, and affect its cell biology, morphology and homeostasis. Many bacteria are however potential pathogens, especially if the integrity of the epithelial barrier is physically or functionally breached. Conversely, the interaction between host and commensal microbes can confer important health benefit...

Several hundred species of bacteria inhabit the gut, and affect its cell biology, morphology and homeostasis. Many bacteria are however potential pathogens, especially if the integrity of the epithelial barrier is physically or functionally breached. Conversely, the interaction between host and commensal microbes can confer important health benefit...

In the present study, we have investigated the role of cholesterol in maintaining the barrier properties of the model intestinal cell line Caco-2. We have extracted membrane cholesterol using methyl-beta-cyclodextrin and demonstrated that maximally, methyl-beta-cyclodextrin lowered cell cholesterol levels by 40-45%. Depletion of cell cholesterol wa...