Secretion Of Antimicrobial Peptides Research Articles

Can mesenchymal stem/stromal cells and their secretomes combat bacterial persisters?

The increasing number of life-threatening infections caused by persister bacteria is associated with various issues, including antimicrobial resistance and biofilm formation. Infections due to persister cells are often difficult to suppress without the use of last-resort antibiotics. Throughout the world, bacterial persistence and resistance create an unmet clinical demand for the exploration of newly introduced therapeutic approaches. Mesenchymal stem / stromal cells (MSCs) have an antimicrobial activity to protect against bacterial infections, including those caused by bacterial persisters. MSCs have substantial potential to secrete antimicrobial peptides (AMPs), including cathelicidin, beta-defensins, lipocalin-2, hepcidin, indoleamine 2,3-dioxygenase (IDO), cysteine proteases, and inducible nitric oxide synthases (iNOS). MSCs possess the potential to contribute to innate immunity by regulating the immune response. Recently, MSCs and their secreted components have been reported to improve antimicrobial activity. Bactericidal activity by MSCs and their secretomes has been shown to be mediated in part by the secretion of AMPs. Even though they were discovered more than 80 years ago, therapeutic options for persisters are restricted, and there is an urgent need for alternative treatment regimens. Hence, this review intends to critically assess the current literature on the effects of MSCs and their secretomes on persister bacteria. MSCs and their secretome-based therapies could be preferred as an up-and-coming approach to reinforce the antimicrobial efficiency in persister infections.

Population Dynamics of Intestinal Enterococcus Modulate Galleria mellonella Metamorphosis.

Microbes found in the digestive tracts of insects are known to play an important role in their host's behavior. Although Lepidoptera is one of the most varied insect orders, the link between microbial symbiosis and host development is still poorly understood. In particular, little is known about the role of gut bacteria in metamorphosis. Here, we explored gut microbial biodiversity throughout the life cycle of Galleria mellonella, using amplicon pyrosequencing with the V1 to V3 regions, and found that Enterococcus spp. were abundant in larvae, while Enterobacter spp. were predominant in pupae. Interestingly, eradication of Enterococcus spp. from the digestive system accelerated the larval-to-pupal transition. Furthermore, host transcriptome analysis demonstrated that immune response genes were upregulated in pupae, whereas hormone genes were upregulated in larvae. In particular, regulation of antimicrobial peptide production in the host gut correlated with developmental stage. Certain antimicrobial peptides inhibited the growth of Enterococcus innesii, a dominant bacterial species in the gut of G. mellonella larvae. Our study highlights the importance of gut microbiota dynamics on metamorphosis as a consequence of the active secretion of antimicrobial peptides in the G. mellonella gut. IMPORTANCE First, we demonstrated that the presence of Enterococcus spp. is a driving force for insect metamorphosis. RNA sequencing and peptide production subsequently revealed that antimicrobial peptides targeted against microorganisms in the gut of Galleria mellonella (wax moth) did not kill Enterobacteria species, but did kill Enterococcus species, when the moth was at a certain stage of growth, and this promoted moth pupation.

Acute chlorothalonil exposure had the potential to influence the intestinal barrier function and micro-environment in mice

The intestinal barrier maintains intestinal homeostasis and metabolism and protects against harmful pollutants. Some environmental pollutants seriously affect intestinal barrier function. However, it remains unclear whether or how chlorothalonil (CTL) impacts the intestinal barrier function in animals. Herein, 6-week-old male mice were acutely exposed to different CTL concentrations (100 and 300 mg/kg BW) via intragastric administration once a day for 7 days. Histopathological examination revealed obvious inflammation in the mice’ colon and ileum. Most notably, CTL exposure increased the intestinal permeability, particularly in the CTL-300 group. CTL exposure reduced the secretion of colonic epithelial mucus and changed the transcription levels of genes bound up with ion transport and ileal antimicrobial peptide (AMP) secretion, indicating intestinal chemical barrier damage. The results of terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay and Ki67 staining revealed abnormal apoptosis and increased intestinal epithelial cell proliferation, suggesting that CTL exposure led to cytotoxicity and inflammation. The results of 16S rRNA sequencing revealed that CTL exposure altered the intestinal microbiota composition and reduced its diversity and richness in the colon contents. Thus, acute CTL exposure affected the different intestinal barrier- and gut microenvironment-related endpoints in mice.

Dynamics of the innate immune response profile in patients with coronary heart disease at different terms after coronary artery stenting

Atherosclerosis is accompanied by damage to the vascular endothelium of arteries followed by development of inflammatory response and formation of atherosclerotic plaques. Innate immunity is an important component of this response being the earliest non-specific key mechanism. Our objective was to perform a comprehensive assessment of the cellular link of innate immunity, and to compare the results obtained at various terms after coronary stenting.The study involved 50 patients with coronary atherosclerosis (Group 1), who had clinical indications for stenting of coronary arteries, and 20 volunteers (Group 2), who have no signs of coronary artery disease. The study of immune parameters was carried out before surgery, at 4-5, 9-10 and 28-30 days after operation (during early postoperative period), as well as 6 and 12 months after stenting, i.e. over the late post-surgical period. Phenotyping of peripheral blood monocytes and lymphocytes was performed by flow cytometry using monoclonal antibodies (Beckman Coulter, USA). Intracellular content of Granzyme B was carried out with an FC500 flow laser cytofluorimeter. Metabolic activity of neutrophils was assessed by the NBT test. Alpha defensin was determined in blood plasma by ELISA technique (Hycult Biotech, USA). Statistical analysis was performed using the Statistica 12.0 program (StatSoft, USA). Statistical significance was considered significant at p ≤ 0.05.The numbers of natural killer cells and their activity, as well as those of monocytes, were increased in patients with coronary atherosclerosis. We have also shown a suppression of antigen presentation processes, an imbalance in microbicidal activity of neutrophils, with predominant secretion of antimicrobial peptides. Over the early post-surgical period, significant changes included only decreased content of intracellular Granzyme B on days 4-5, and expression of TLR4 and HLA-DR on days 4-5 and 9-10. During the late period, the patients with coronary artery disease exhibited a significant decrease in the content of some lymphocyte subsets: CD3+CD16+, CD16+Gr+ as well as amounts of monocytes: CD14+CD282+, CD14+CD284+, CD14+CD289+, along with HBT-test activity and α-defensin contents, and increased numbers of HLA-DR-expressing monocytes.There are changes in cellular component of innate immunity, indicating persistent inflammation in patients with coronary heart disease. The dynamics of revealed changes following coronary artery stenting may reflect a lability of assessed indicators mostly over the late postoperative period, thus serving a basis for predicting the outcome of coronary stenting.

Symbiotic Bacteria Modulate Lymantria dispar Immunity by Altering Community Proportions after Infection with LdMNPV.

The symbiotic bacteria-insect interaction is considered to be associated with immunity and drug resistance. However, the wide variety of insect species and habitats is thought to have a significant impact on the symbiotic community, leading to disparate results. Here, we demonstrated that symbiotic bacteria regulated the immune response by changing the proportion of the Gram-positive and the Gram-negative bacterial community in Lymantria dispar (L. dispar) after infection with its viral pathogen, L. dispar Nucleopolyhedrovirus (LdMNPV). After oral infection, the immune deficiency pathway was activated immediately, and the expression of Relish was up-regulated to promote the secretion of antimicrobial peptides. Meanwhile, the abundance of the Gram-negative bacterial community increased at the same time. Moreover, the Toll pathway was not regulated in the same way as the Imd pathway was after infection. However, the change in the Toll pathway's expression remained positively correlated to the abundance of Gram-positive bacteria. This finding implied that the ratio of Gram-negative to Gram-positive bacteria in the LdMNPV infected larvae had an effect on the immune response. Our findings revealed that the immune regulation of L. dispar was regulated by the relative abundance of its symbiotic bacteria at different infection times with LdMNPV, which provides a new way to understand symbiotic bacteria-insect interactions.

Differences in fish mucus proteomes identify potential antimicrobial peptide biomarkers

We compared the secretion of antimicrobial peptides (AMPs) in the epidermal mucus of three healthy fish species: two aquacultured teleost species, Dicentrarchus labrax and Sparus aurata, and one wild-caught species, Pagrus pagrus. The AMPs detected in all mucus by LC-MS/MS-QTOF are: Chrysophsin-1, -2 and -3, Piscidins −1, −2, −3 and −4, terminal Histone parts and Hepcidin-like peptides. Secretion analysis of the mucus from aquacultured fish using ProGenesis IQ software distinguished the bactericidal activities of histone peptides and probiotic flora from those of other AMPs. Chrysophsin-1 was statistically the most abundant peptide in both mucus samples (p < 0.0035). A lower detection of Piscidins was also observed. Interestingly, the presence of Oncorhyncin I was most pronounced in Sparus aurata mucus. Altogether, these results suggest that Chrysophsin-1 and Oncorhyncin I are potential biomarkers for immunodetection-based studies of changes in secretion patterns which will be further investigated during bacterial challenge.

Live and pasteurized Akkermansia muciniphila decrease susceptibility to Salmonella Typhimurium infection in mice

IntroductionThe gut microbiome is vital for providing resistance against colonized pathogenicbacteria. Recently, specific commensal species have become recognized as important mediators of host defense against microbial infection by a variety of mechanisms. ObjectivesTo examine the contribution of live and pasteurized A. muciniphila to defend against the intestinal pathogen Salmonella Typhimurium in a streptomycin-treated mouse model of infection. MethodsC57B6J mice were pretreated with phosphate-buffered saline (PBS), live Akkermansia muciniphila (AKK), and pasteurized A. muciniphila (pAKK) for two weeks, then mice were infected by S. Typhimurium SL 1344. 16S rRNA-based gut microbiota analysis was performed before and after infection. Bacterial counts in feces and tissues, histopathological analysis, gut barrier-related gene expression, and antimicrobial peptides were examined. Co-housing was performed to examine the role of microbiota in the change of susceptibility of mice to infection. ResultsAKK and pAKK markedly decreased Salmonella fecal and systemic burdens and reduced inflammation during infection. Notably, further characterization of AKK and pAKK protective mechanisms revealed different candidate protective pathways. AKK promoted gutbarrier gene expression and the secretion of antimicrobial peptides, and co-housing studies suggested that AKK-associated microbial community played a role in attenuating infection. Moreover, pAKK had a positive effect on NLRP3 in infected mice. We verified that pretreatment of pAKK could promote the expression of NLRP3, and enhance the antimicrobial activity of macrophage, likely through increasing the production of reactive oxygen (ROS), nitric oxide (NO), and inflammatory cytokines. ConclusionOur study demonstrates that live or pasteurized A. muciniphila can be effective preventive measures for alleviating S. Typhimurium-induced disease, highlighting the potential of developing Akkermansia-based probiotics or postbiotics for the prevention of Salmonellosis.

From birth to death: The hardworking life of Paneth cell in the small intestine.

Paneth cells are a group of unique intestinal epithelial cells, and they play an important role in host-microbiota interactions. At the origin of Paneth cell life, several pathways such as Wnt, Notch, and BMP signaling, affect the differentiation of Paneth cells. After lineage commitment, Paneth cells migrate downward and reside in the base of crypts, and they possess abundant granules in their apical cytoplasm. These granules contain some important substances such as antimicrobial peptides and growth factors. Antimicrobial peptides can regulate the composition of microbiota and defend against mucosal penetration by commensal and pathogenic bacteria to protect the intestinal epithelia. The growth factors derived from Paneth cells contribute to the maintenance of the normal functions of intestinal stem cells. The presence of Paneth cells ensures the sterile environment and clearance of apoptotic cells from crypts to maintain the intestinal homeostasis. At the end of their lives, Paneth cells experience different types of programmed cell death such as apoptosis and necroptosis. During intestinal injury, Paneth cells can acquire stem cell features to restore the intestinal epithelial integrity. In view of the crucial roles of Paneth cells in the intestinal homeostasis, research on Paneth cells has rapidly developed in recent years, and the existing reviews on Paneth cells have mainly focused on their functions of antimicrobial peptide secretion and intestinal stem cell support. This review aims to summarize the approaches to studying Paneth cells and introduce the whole life experience of Paneth cells from birth to death.

An Overview on the Function of Probiotics and Their Positive Effects on Enhancing Intestinal Immune Responses

Probiotics are alive and beneficial microorganisms that affect the body’s microbial flora when consumed by humans or animals and have beneficial effects on the health of the host. Nowadays, probiotics are considered a factor in the prevention of many infectious diseases and cancers. Given the particular importance of probiotics, this study aimed to narratively review previous studies on the mode of action of probiotics and the beneficial effects of probiotics on enhancing intestinal immune responses. Articles on this topic were searched in Google Scholar, Springer, Science Direct, and Clinical Trial databases, and systematic review articles examining the effects of probiotics on the function of the intestinal immune response were included in the study. The results of the research showed that probiotics can boost the body’s immune system, break down food due to their ability to produce enzymes, lower the pH of the environment, and secrete bacteriocins. Furthermore, the effect of probiotics on the modulation mechanisms of the innate defense responses of the intestinal epithelium, including the stimulation of trefoil factor 3, induction of antimicrobial peptide (AMP) secretion, stimulation of secretory immunoglobulin production, and stimulation of toll-like receptors increase in heat shock protein production, modulation of P-glycoprotein (P-gp) and regulation of mucins by probiotics. Therefore, probiotics are expected to be used as an adjunct treatment for many digestive and infectious diseases.

Autophagy and the Insulin-like Growth Factor (IGF) System in Colonic Cells: Implications for Colorectal Neoplasia.

Colorectal cancer (CRC) is one of the most common human malignancies worldwide. Along with apoptosis and inflammation, autophagy is one of three important mechanisms in CRC. The presence of autophagy/mitophagy in most normal mature intestinal epithelial cells has been confirmed, where it has mainly protective functions against reactive oxygen species (ROS)-induced DNA and protein damage. Autophagy regulates cell proliferation, metabolism, differentiation, secretion of mucins and/or anti-microbial peptides. Abnormal autophagy in intestinal epithelial cells leads to dysbiosis, a decline in local immunity and a decrease in cell secretory function. The insulin-like growth factor (IGF) signaling pathway plays an important role in colorectal carcinogenesis. This is evidenced by the biological activities of IGFs (IGF-1 and IGF-2), IGF-1 receptor type 1 (IGF-1R) and IGF-binding proteins (IGF BPs), which have been reported to regulate cell survival, proliferation, differentiation and apoptosis. Defects in autophagy are found in patients with metabolic syndrome (MetS), inflammatory bowel diseases (IBD) and CRC. In neoplastic cells, the IGF system modulates the autophagy process bidirectionally. In the current era of improving CRC therapies, it seems important to investigate the exact mechanisms not only of apoptosis, but also of autophagy in different populations of tumor microenvironment (TME) cells. The role of the IGF system in autophagy in normal as well as transformed colorectal cells still seems poorly understood. Hence, the aim of the review was to summarize the latest knowledge on the role of the IGF system in the molecular mechanisms of autophagy in the normal colon mucosa and in CRC, taking into account the cellular heterogeneity of the colonic and rectal epithelium.

IL-17-driven induction of Paneth cell antimicrobial functions protects the host from microbiota dysbiosis and inflammation in the ileum

IL-17 protects epithelial barriers by inducing the secretion of antimicrobial peptides (AMPs). However, the effect of IL-17 on Paneth cells (PCs), the major producers of AMPs in the small intestine, is unclear. Here, we show that targeted ablation of the IL-17 receptor (IL-17R) in PCs disrupts their antimicrobial functions and decreases the frequency of ileal PCs. These changes become more pronounced after colonization with IL-17 inducing segmented filamentous bacteria (SFB). Mice with PCs that lack IL-17R show an increased inflammatory transcriptional profile in the ileum along with the severity of experimentally induced ileitis. These changes are associated with a decrease in the diversity of gut microbiota that induces a severe ileum pathology upon transfer to genetically susceptible mice which can be prevented by the systemic administration of IL-17a/f in microbiota recipients. In an exploratory analysis of a small cohort of pediatric patients with Crohn's disease, we have found that a portion of these patients exhibit a low number of lysozyme-expressing ileal PCs and a high ileitis severity score, resembling the phenotype of mice with IL-17R-deficient PCs. Our study identifies IL-17R-dependent signaling in PCs as an important mechanism that maintains ileal homeostasis through the prevention of dysbiosis.

SG-APSIC1137: 12-hydroxystearic acid upregulates skin antimicrobial peptides in skin models and provides long-lasting protection from bacterial challenge from a handwash formulation

Objectives: We evaluated the role of 12-hydroxystearic acid (12HSA) in upregulating skin antimicrobial peptides (AMPs) in in vitro and ex vivo assays, and 12HSA provides long-lasting germ protection in vivo through a handwash formulation. Methods: In vitro assays were performed by treating skin cells, maintained in cell-culture media, with 12HSA. After treatment, AMP gene-expression was measured in cells by RT-qPCR, and secreted AMPs in spent cell culture media were analyzed by ELISA. Skin explants were treated with 12HSA, and 3D-living skin equivalent (LSE) models were treated with 12HSA-containing handwash formulations. AMP levels were measured by immunohistochemical staining or RT-qPCR after treatment. In clinical studies, volunteer forearms were washed multiple times with 12HSA-containing handwash in an ethics-approved study in which participants provided informed consent. The washed forearms were challenged with E. coli at different time points after washing. The 12HSA deposition from the formulation was measured using tape strips. Results: Skin cells treated with 12HSA showed increased expression of several AMP genes in vitro, and higher psoriasin AMP secretion was measured in cell-culture media. An enhanced level of LL37 AMP was obtained from the skin epidermis of 12HSA-treated explant skin. AMP genes were also upregulated in the 3D-LSE model treated with a 12HSA-containing handwash formulation. A measurable level of 12HSA was deposited from handwash formulation in the in vivo clinical sample. E. coli recovery from challenged skin was significantly lower at 6 and 10 hours after washing compared to unwashed skin. Conclusions: These data demonstrate that 12HSA boosts skin-AMPs and that a handwash containing 12HSA provides long-lasting germ protection under in vivo test conditions by potentially enhancing skin’s natural immunity. With an emerging understanding of skin’s innate immunity and AMPs, designing cleansing products that strengthen these natural defenses will offer novel approaches to extend hygiene benefits beyond immediate in-wash protection.

Antimicrobial peptides — the first line of immune defense of the oral mucous membranes

Inflammatory diseases of the oral cavity are a serious medical and social problem, which is caused by a large variety of opportunistic bacteria and an increase in the resistance of microorganisms to antibiotics in the treatment of various nosological forms. One of these common diseases of the oral mucosa is periodontitis. Among bacteria, Actinobacillus actinomycetem comitans, Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola, Fusobacterium nucleatum, Eubacterium nodatum, Prevotella intermedia and Prevotella nigrescens have a leading influence on the development of periodontitis. Timely detection and treatment of periodontitis prevents the development of more serious periodontal diseases. A large number of microbes, penetrating into the oral cavity, are neutralized on the mucous membrane. Antimicrobial peptides play an important role in protecting against opportunistic pathogens on the oral mucosa. The review considers in detail three main classes of antimicrobial peptides: cathelicidins, defensins, and histatins. A detailed analysis of the production of the main antimicrobial peptides of the oral cavity in periodontitis was carried out. It has been shown that in the acute and chronic course of diseases of the oral cavity, the synthesis of some antimicrobial peptides decreases, while others increase. The knowledge gained can be used to develop therapeutic drugs based on antimicrobial peptides. Changes in the secretion of antimicrobial peptides, as well as tissue destruction products resulting from inflammation in the oral cavity, are potential targets for diagnosing diseases of the oral cavity. Therefore, the production of antimicrobial peptides in periodontitis indicates that this class of proteins can be used not only for treatment, but also for the diagnosis of periodontal diseases.

529 UVB inhibits staphylococcus aureus growth through action on skin commensals

Staphylococcus aureus (S.aureus) plays a crucial role in the pathogenesis of atopic dermatitis (AD) via the secretion of several virulence factors that can exacerbate the disease. S.aureus growth and virulence inhibition is one of the potential therapeutic approaches in AD treatment. Ultraviolet radiation (UVR)-based phototherapy is one of the widely used treatment options for AD with a favourable benefit-risk ratio. UVR has been shown being able inducing antimicrobial peptides (AMP). We therefore hypothesize that the therapeutic efficacy of UVR is at least partly due to its ability to induce AMP secretion not only from the host cells, but also from certain skin resident microbes.

The Toll pathway mediates Drosophila resilience to Aspergillus mycotoxins through specific Bomanins

Host defense against infections encompasses both resistance, which targets microorganisms for neutralization or elimination, and resilience/disease tolerance, which allows the host to withstand/tolerate pathogens and repair damages. In Drosophila, the Toll signaling pathway is thought to mediate resistance against fungal infections by regulating the secretion of antimicrobial peptides, potentially including Bomanins. We find that Aspergillus fumigatus kills Drosophila Toll pathway mutants without invasion because its dissemination is blocked by melanization, suggesting a role for Toll in host defense distinct from resistance. We report that mutants affecting the Toll pathway or the 55C Bomanin locus are susceptible to the injection of two Aspergillus mycotoxins, restrictocin and verruculogen. The vulnerability of 55C deletion mutants to these mycotoxins is rescued by the overexpression of Bomanins specific to each challenge. Mechanistically, flies in which BomS6 is expressed in the nervous system exhibit an enhanced recovery from the tremors induced by injected verruculogen and display improved survival. Thus, innate immunity also protects the host against the action of microbial toxins through secreted peptides and thereby increases its resilience to infection.

TLR-activated mesenchymal stromal cell therapy and antibiotics to treat multi-drug resistant Staphylococcal septic arthritis in an equine model.

Rapid development of antibiotic resistance necessitates advancement of novel therapeutic strategies to treat infection. Mesenchymal stromal cells (MSC) possess antimicrobial and immunomodulatory properties, mediated through antimicrobial peptide secretion and recruitment of innate immune cells including neutrophils and monocytes. TLR-3 activation of human, canine and equine MSC has been shown to enhance bacterial killing and clearance in vitro, in rodent Staphylococcal biofilm infection models and dogs with spontaneous multi-drug-resistant infections. The objective of this study was to determine if intra-articular (IA) TLR-3-activated MSC with antibiotics improved clinical parameters and reduced bacterial counts and inflammatory cytokine concentrations in synovial fluid (SF) of horses with induced septic arthritis. Eight horses were inoculated in one tarsocrural joint with multidrug-resistant Staphylococcus aureus (S. aureus). Bone marrow-derived MSC from three unrelated donors were activated with TLR-3 agonist polyinosinic, polycytidylic acid (pIC). Recipient horses received MSC plus vancomycin (TLR-MSC-VAN), or vancomycin (VAN) alone, on days 1, 4, 7 post-inoculation and systemic gentamicin. Pain scores, quantitative bacterial counts (SF, synovium), SF analyses, complete blood counts, cytokine concentrations (SF, plasma), imaging changes (MRI, ultrasound, radiographs), macroscopic joint scores and histologic changes were assessed. Results were reported as mean ± SEM. Pain scores (d7, P=0.01, 15.2±0.2 vs. 17.9±0.5), ultrasound (d7, P=0.03, 9.0±0.6 vs. 11.8±0.5), quantitative bacterial counts (SF d7, P=0.02, 0±0 vs. 3.4±0.4; synovium P=0.003, 0.4±0.4 vs. 162.7±18.4), systemic neutrophil (d4, P=0.03, 4.6±0.6 vs. 7.8±0.6) and serum amyloid A (SAA) (d4, P=0.01, 1,106.0±659.0 vs. 2,858.8±141.3; d7, P=0.02, 761.8±746.2 vs. 2,357.3±304.3), and SF lactate (d7, P<0.0001, 5.4±0.2 vs. 15.0±0.3), SAA (endterm, P=0.01, 0.0 vs. 2,094.0±601.6), IL-6 (P=0.03, 313.0±119.2 vs. 1,328.2±208.9), and IL-18 (P=0.02, 11.1±0.5 vs. 13.3±3.8) were improved in TLR-MSC-VAN vs. VAN horses. Study limitations include the small horse sample size, short study duration, and lack of additional control groups. Combined TLR-activated MSC with antibiotic therapy may be a promising approach to manage joint infections with drug resistant bacteria.

33255 Handwash formulations containing 12-hydroxystearic acid provide long-lasting protection against bacteria in vivo

Antimicrobial peptides (AMPs) are part of skin’s innate immune system and help protect from infections. 12-hydroxystearic acid (12HSA) is a well-known cosmetic ingredient used for skin appearance and barrier-building benefits. It is believed that 12HSA deposited through cosmetic formulations could provide long-lasting protection against pathogenic microbes by modulating the skin’s innate immune response. The objective of this research was to investigate if a handwash containing 12HSA could provide enhanced protection against a test microbe in vivo, through increased AMP secretion as measured from skin cells in vitro and ex vivo.

33255 Handwash formulations containing 12-hydroxystearic acid provide long-lasting protection against bacteria in vivo

Antimicrobial peptides (AMPs) are part of the skin’s innate immune system and help protect from infections. 12-hydroxystearic acid (12HSA) is a well-known cosmetic ingredient used for skin appearance and barrier-building benefits. It is believed that 12HSA deposited through cosmetic formulations could provide long-lasting protection against pathogenic microbes by modulating the skin’s innate immune response. The objective of this research was to investigate if a handwash containing 12HSA could provide enhanced protection against a test microbe in vivo, through increased AMP secretion as measured from skin cells in vitro and ex vivo.

PARP1 inhibition enhances reactive oxygen species on gut microbiota.

Poly(ADP-ribose) polymerase 1 (PARP1) plays a key role in genome stability by modulating DNA-damage responses. Activated by DNA interruptions through ultraviolet (UV) exposure, PARylation is synthesized by PARP1 and serves as a survival mechanism for cancer and metabolic diseases. Several strategies including ROS and antimicrobial peptides(AMPs) function in host defenses, while the targeted tissue and mechanism under DNA damage are unknown. Here, we show that DNA damage induces responses specifically in the gut tissue. The knockdown of PARP1 reduces the activation of PARylation. Parp1 knockdown under DNA damage results in over-accumulated ROS and secretion of AMPs through the regulation of Relish, a subunit of nuclear factor-κB(NF-κB). Double-knockdown of Parp1 and Relish specifically in the gut inhibits AMP secretion. In conclusion, the host defense is achieved through ROS accumulation rather than the AMPs under DNA damage. In contrast, the knockdown of PARP1 exacerbates ROS accumulation to a harmful level. Under this circumstance, NF-κb targeted AMP secretion is provoked for host defense. Microbiome and functional analysis provide evidence for the hazard of DNA damage and show variations in the metabolic pathways following Parp1 inhibition. Our findings suggest the notion that PARP1 inhibition contributes to ROS accumulation under DNA damage and its role in NF-κb activation for host defense.

Akkermansia muciniphila Colonization Alleviating High Fructose and Restraint Stress-Induced Jejunal Mucosal Barrier Disruption.

Akkermansia muciniphila (A. muciniphila) is a mucin-degrading bacterium that resides in the mucus layer, but its potential in intestinal inflammatory diseases has sparked controversy. It is well known that both the consumption of fructose-containing beverages and psychological stress increase the risk of intestinal disease. Our results revealed that a high-fructose diet aggravated the damage to the jejunal mucosal barrier caused by restraint stress, reduced tight junction protein expression and the intestinal digestion and absorption capacity, disrupted the ability of Paneth cells to secrete antimicrobial peptides, and promoted the expression of inflammatory cytokines. A. muciniphila colonization enhanced the defense function of the mucosal barrier by enhancing the function of the NLRP6, promoting autophagy, maintaining the normal secretion of antimicrobial peptides in Paneth cells, promoting the expression of tight junction proteins, negatively regulating the NF-kB signaling pathway and inhibiting the expression of inflammatory cytokines. Our work indicates that A. muciniphila ameliorates the disruption of the intestinal mucosal barrier under high fructose and restraint stress. These results provided a rationale for the development of probiotic colonization for the prevention or treatment of intestinal diseases.