Diabetic foot ulcers (DFU) are a growing concern worldwide as they pose complications in routine clinical practices such as diagnosis and management. Bacterial interactions on the skin surface are vital to the pathophysiology of DFU and may control delayed wound healing. The microbiota from our skin directly regulates cutaneous health and disease by interacting with the numerous cells involved in the wound healing mechanism. Commensal microbiota, in particular, interact with wound-repairing skin cells to enhance barrier regeneration. The observed microbes in DFU include Staphylococcus, Streptococcus, Corynebacterium, Pseudomonas, and several anaerobes. Skin commensal microbes, namely S. epidermidis, can regulate the gamma delta T cells and induce Perforin-2 expression. The increased expression of Perforin-2 by skin cells destroyed S. aureus within the cells, facilitating wound healing. Possible crosstalk between the human commensal microbiome and different cell types involved in cutaneous wound healing promotes the immune response and helps to maintain the barrier function in humans. Wound healing is a highly well-coordinated, complex mechanism; it can be devastating if interrupted. Skin microbiomes are being studied in relation to the gut-skin axis along with their effects on dermatologic conditions. The gut-skin axis illustrates the connection wherein the gut can impact skin health due to its immunological and metabolic properties. The precise mechanism underlying gut-skin microbial interactions is still unidentified, but the immune and endocrine systems are likely to be involved. Next-generation sequencing and the development of bioinformatics pipelines may considerably improve the understanding of the microbiome-skin axis involved in diabetic wound healing in a much more sophisticated way. We endeavor to shed light on the importance of these pathways in the pathomechanisms of the most prevalent inflammatory conditions including the diabetes wound healing, as well as how probiotics may intervene in the gut-skin axis.

Acne dysbiosis happens when there is a microbial imbalance of the over-growth of Propionibacterium acnes (P. acnes) in the acne microbiome. In our previous study, we demonstrated that Staphylococcus epidermidis (S. epidermidis, a probiotic skin bacterium) can exploit glycerol fermentation to produce short-chain fatty acids (SCFAs) which have antimicrobial activities to suppress the growth of P. acnes. Unlike glycerol, sucrose is chosen here as a selective fermentation initiator (SFI) that can specifically intensify the fermentation activity of S. epidermidis, but not P. acnes. A co-culture of P. acnes and fermenting S. epidermidis in the presence of sucrose significantly led to a reduction in the growth of P. acnes. The reduction was abolished when P. acnes was co-cultured with non-fermenting S. epidermidis. Results from nuclear magnetic resonance (NMR) analysis revealed four SCFAs (acetic acid, butyric acid, lactic acid, and succinic acid) were detectable in the media of S. epidermidis sucrose fermentation. To validate the interference of S. epidermidis sucrose fermentation with P. acnes, mouse ears were injected with both P. acnes and S. epidermidis plus sucrose or phosphate buffered saline (PBS). The level of macrophage-inflammatory protein-2 (MIP-2) and the number of P. acnes in ears injected with two bacteria plus sucrose were considerably lower than those in ears injected with two bacteria plus PBS. Our results demonstrate a precision microbiome approach by using sucrose as a SFI for S. epidermidis, holding future potential as a novel modality to equilibrate dysbiotic acne.

Endogenous alcohol produced by the gut microbiome is transported via the bloodstream to the liver for detoxification. Gut dysbiosis can result in chronic excess alcohol production that contributes to the development of hepatic steatosis. The aim of this study was to examine whether linolenic acid can manipulate the production of harmful alcohol and beneficial short-chain fatty acids (SCFAs) in the metabolome of commensal Klebsiella pneumoniae (K. pneumoniae) and the virulent K. pneumoniae K1 serotype. Glucose fermentation by the K. pneumoniae K1 serotype yielded increased production of alcohol and decreased SCFAs (especially acetate and propionate) compared to those of commensal K. pneumoniae. However, the use of linolenic acid instead of glucose significantly reduced alcohol and increased SCFAs in the fermentation media of the K. pneumoniae K1 serotype. The work highlights the value of shaping the microbial metabolome using linolenic acid, which can potentially regulate the gut–liver axis for the prevention and treatment of alcohol-induced liver diseases.

Amidst infectious disease outbreaks, a practical tool that can quantitatively monitor individuals’ antibodies to pathogens is vital for disease control. The currently used serological lateral flow immunoassays (LFIAs) can only detect the presence of antibodies for a single antigen. Here, we fabricated a multiplexed circular flow immunoassay (CFIA) test strip with YOLO v4-based object recognition that can quickly quantify and differentiate antibodies that bind membrane glycoprotein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or hemagglutinin of influenza A (H1N1) virus in the sera of immunized mice in one assay using one sample. Spot intensities were found to be indicative of antibody titers to membrane glycoprotein of SARS-CoV-2 and were, thus, quantified relative to spots from immunoglobulin G (IgG) reaction in a CFIA to account for image heterogeneity. Quantitative intensities can be displayed in real time alongside an image of CFIA that was captured by a built-in camera. We demonstrate for the first time that CFIA is a specific, multi-target, and quantitative tool that holds potential for digital and simultaneous monitoring of antibodies recognizing various pathogens including SARS-CoV-2.

Bromhidrosis is characterized as a chronic condition related to malodor from the skin. The underlying etiology is from bacterial decompositions of glandular secretion products. However, specific pathways and metabolites for the disease are yet to be investigated. Here, twenty-eight metabolites, including fifteen major sweat constituents and thirteen compounds emitted from malodor-producing skin bacteria, were subjected to the metabometric analysis using Metaboanalyst. Different pathways in the butanoate metabolism revealed that acetolactate synthase (ALS) in skin Staphylococcus epidermidis (S. epidermidis) bacteria are catalyzing pyruvate to several malodor compounds like diacetyl. In the docking studies of the sulfonylurea-ALS interaction, five selected sulfonylureas, which originally were developed for the treatment of diabetes mellitus type 2, showed different binding free energies (ΔG) from chlorimuron ethyl - a well-known ALS sulfonylurea inhibitor. Amongst five sulfonylureas, gliquidone and glisoxepide were found to have free energy differences that were lower than or equal to chlorimuron ethyl, revealing their high affinities to ALS. In the future, further investigations of gliquidone and glisoxepide against ALS in skin bacteria would be crucial in repurposing these two sulfonylureas as new anti-bromhidrosis drugs.