Colonization of nasal cavities by Staphylococcus epidermidis mitigates SARS-CoV-2 nucleocapsid phosphoprotein-induced interleukin (IL)-6 in the lung.

Infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can trigger excessive interleukin (IL)-6 signalling, leading to a myriad of biological effects including a cytokine storm that contributes to multiple organ failure in severe coronavirus disease 2019 (COVID-19). Using a mouse model, we demonstrated that nasal inoculation of nucleocapsid phosphoprotein (NPP) of SARS-CoV-2 increased IL-6 content in bronchoalveolar lavage fluid (BALF). Nasal administration of liquid coco-caprylate/caprate (LCC) onto Staphylococcus epidermidis (S. epidermidis)-colonized mice significantly attenuated NPP-induced IL-6. Furthermore, S. epidermidis-mediated LCC fermentation to generate electricity and butyric acid that promoted bacterial colonization and activated free fatty acid receptor 2 (Ffar2) respectively. Inhibition of Ffar2 impeded the effect of S. epidermidis plus LCC on the reduction of NPP-induced IL-6. Collectively, these results suggest that nasal S. epidermidis is part of the first line of defence in ameliorating a cytokine storm induced by airway infection of SARS-CoV-2.

Electricity-producing Staphylococcus epidermidis counteracts Cutibacterium acnes.

Staphylococcus epidermidis (S. epidermidis) ATCC 12228 was incubated with 2% polyethylene glycol (PEG)-8 Laurate to yield electricity which was measured by a voltage difference between electrodes. Production of electron was validated by a Ferrozine assay. The anti-Cutibacterium acnes (C. acnes) activity of electrogenic S. epidermidis was assessed in vitro and in vivo. The voltage change (~ 4.4 mV) reached a peak 60 min after pipetting S. epidermidis plus 2% PEG-8 Laurate onto anodes. The electricity produced by S. epidermidis caused significant growth attenuation and cell lysis of C. acnes. Intradermal injection of C. acnes and S. epidermidis plus PEG-8 Laurate into the mouse ear considerably suppressed the growth of C. acnes. This suppressive effect was noticeably reversed when cyclophilin A of S. epidermidis was inhibited, indicating the essential role of cyclophilin A in electricity production of S. epidermidis against C. acnes. In summary, we demonstrate for the first time that skin S. epidermidis, in the presence of PEG-8 Laurate, can mediate cyclophilin A to elicit an electrical current that has anti-C. acnes effects. Electricity generated by S. epidermidis may confer immediate innate immunity in acne lesions to rein in the overgrowth of C. acnes at the onset of acne vulgaris.

Leuconostoc mesenteroides fermentation produces butyric acid and mediates Ffar2 to regulate blood glucose and insulin in type 1 diabetic mice.

Type 1 diabetic patients have lower counts of butyric acid-producing bacteria in the dysbiotic gut microbiome. In this study, we demonstrate that a butyric acid-producing Leuconostoc mesenteroides (L. mesenteroides) EH-1 strain isolated from Mongolian curd cheese can reduce blood glucose and IL-6 in the type 1 diabetic mouse model. L. mesenteroides EH-1 fermentation yielded high concentrations of butyric acid both in vitro and in vivo. Butyric acid or L. mesenteroides EH-1 increased the amounts of insulin in Min6 cell culture and streptozotocin (STZ)-induced diabetic mice. Inhibition or siRNA knockdown of free fatty acid receptor 2 (Ffar2) considerably reduced the anti-diabetic effect of probiotic L. mesenteroides EH-1 or butyric acid by lowering the level of blood glucose. We here demonstrate that Ffar2 mediated the effects of L. mesenteroides EH-1 and butryic acid on regulation of blood glucose and insulin in type 1 diabetic mice.

A Derivative of Butyric Acid, the Fermentation Metabolite of Staphylococcus epidermidis, Inhibits the Growth of a Staphylococcus aureus Strain Isolated from Atopic Dermatitis Patients.

The microbiome is a rich source of metabolites for the development of novel drugs. Butyric acid, for example, is a short-chain fatty acid fermentation metabolite of the skin probiotic bacterium Staphylococcus epidermidis (S. epidermidis). Glycerol fermentation of S. epidermidis resulted in the production of butyric acid and effectively hindered the growth of a Staphylococcus aureus (S. aureus) strain isolated from skin lesions of patients with atopic dermatitis (AD) in vitro and in vivo. This approach, however, is unlikely to be therapeutically useful since butyric acid is malodorous and requires a high concentration in the mM range for growth suppression of AD S. aureus. A derivative of butyric acid, BA-NH-NH-BA, was synthesized by conjugation of two butyric acids to both ends of an -NH-O-NH- linker. BA-NH-NH-BA significantly lowered the concentration of butyric acid required to inhibit the growth of AD S. aureus. Like butyric acid, BA-NH-NH-BA functioned as a histone deacetylase (HDAC) inhibitor by inducing the acetylation of Histone H3 lysine 9 (AcH3K9) in human keratinocytes. Furthermore, BA-NH-NH-BA ameliorated AD S. aureus-induced production of pro-inflammatory interleukin (IL)-6 and remarkably reduced the colonization of AD S. aureus in mouse skin. These results describe a novel derivative of a skin microbiome fermentation metabolite that exhibits anti-inflammatory and S. aureus bactericidal activity.

Moderate-intensity exercise training elevates serum and pancreatic zinc levels and pancreatic ZnT8 expression in streptozotocin-induced diabetic rats.

AIMS: Diabetes mellitus is associated with disturbed zinc homeostasis and down-regulation of zinc transporter 8 (ZnT8); these changes contribute to the defective biosynthesis, storage, and secretion of insulin. Previous studies have reported an improvement in diabetic status and insulin levels in diabetic rats that underwent moderate exercise training, but the mechanisms underlying this effect remain unclear. Evidence shows that exercise training increases the zinc content in the muscle, liver, and kidney of diabetic rats and increases the expression of several types of zinc transporters in the rat hippocampus. We hypothesised that moderate exercise training may increase serum and pancreatic zinc levels, as well as pancreatic ZnT8 expression, in diabetic rats. MAIN METHODS: Wistar rats were divided into 3 equally sized groups: sedentary normal control, sedentary diabetic, and exercise-trained diabetic groups. Diabetes was induced by an intraperitoneal injection of streptozotocin. The 6-week exercise training intervention involved 30 min of moderate-intensity running on a treadmill once daily (5 days/week). At the end of the study, the concentrations of serum and pancreatic zinc were determined using atomic absorptive spectrophotometry. Pancreatic ZnT8 expression was analysed by quantitative real-time RT-PCR. KEY FINDINGS: Diabetes caused reductions in the serum and pancreatic zinc levels and pancreatic ZnT8 expression. Following moderate exercise training, there was a significant increase in all of these parameters. SIGNIFICANCE: The ability of moderate exercise training to ameliorate the reductions in serum and pancreatic zinc levels and pancreatic ZnT8 expression can partly explain the beneficial effects of exercise training in diabetes.