Medicine in Microecology最新文献

Introduction

EDP1815 is a single-strain of Prevotella histicola with preclinical immunomodulatory properties. The aim of this study was to evaluate pharmacodynamic effects of EDP1815 on the immune response following immunization with keyhole limpet hemocyanin (KLH) and dermal rechallenge.

Methods

Thirty-two healthy subjects (median 30, range 18–59 years) were randomized over two cohorts to EDP1815 or placebo (12:4). Both cohorts received 8.0 × 10¹¹ total cells daily for 28 days, reconstituted in 10 (A formulation) or 5 (B formulation) capsules. KLH-specific antibodies and circulating regulatory T cells were evaluated. Skin response after rechallenge was assessed with imaging. Immune cell subsets from blister exudates were assessed in the B cohort only. Ex vivo phytohemagglutinin and lipopolysaccharide whole blood challenges were performed to evaluate cytokine release. Gastrointestinal tract persistence, prevalence, and colonization of EDP1815 were assessed by fecal qPCR and microbiome assays. Data were analyzed using repeated measures analysis of covariances.

Results

There was a trend toward a treatment effect on the KLH-induced skin rechallenge response (CIELab a* estimated difference (ED) −1.50 arbitrary unit (AU), 95% CI −3.47–0.47 AU, P = .13, and average redness ED −0.14 AU, 95% CI −0.31–0.03 AU, P = .10 in B cohort) and, to a lesser extent, on the humoral KLH response. No notable EDP1815 effects were observed on gut persistence, microbiome, and other safety parameters.

Conclusion

Based on our findings and the clinical benefit observed in the phase 2 study in psoriasis, further investigation of the immunomodulatory effects and potential clinical benefit of EDP1815 is warranted.

Antimicrobial peptides (AMPs) are compounds that inhibit the growth of bacterial pathogens by preventing microbial colonization in the host. AMPs are usually found in animals, humans, and plants. In particular, AMPs of human origin are released by cells of the immune system in response to microbial infections. Studies have shown that AMPs target virulence proteins of bacterial strains and inhibit the colonization of host tissues. However, over the past few decades, the emergence of drug-resistant pathogenic strains has led to sources for AMPs from green sources such as tropical plants. Such plant-based AMPs (pAMPs) were proven to exhibit antimicrobial activity against several gram-positive, gram-negative, and fungal pathogens. Several studies have demonstrated the presence of pAMPs such as thionins, defensins, snakins, lipid transfer peptides, and knottin-like peptides from a wide range of plant sources. For instance, pAMP such as defensins (CtDef1) from the plant species Clitoria ternatea were proven to inhibit Bacillus subtilis. In addition, such pAMPs are sustainable as they are extracted from green sources such as plants. Therefore, pAMP can potentially combat the threat of drug resistance in pathogenic strains. This review highlights the mechanism of the plant AMPs and their role in killing bacterial cells. In addition, this article also critically evaluates the studies conducted using pAMP conjugated with fluorescent markers to identify the subcellular targets. Overall, this article emphasizes the potential of plant AMPs in mitigating drug resistance.

Aims

This study was designed to investigate the incidence of subgingival Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans infections and their relationship with genetic variability in Saudi Arabian adults with chronic periodontitis and to evaluate the correlation between infection frequency and other variables.

Methods

Multiplex polymerase chain reaction (PCR) assays were developed to detect P. gingivalis 16 ​S rDNA, fimbria (fimA), and collagenase (prtC) genes, as well as the A. actinomycetemcomitans 16 ​S rDNA, leukotoxin (lktA), and fimbria-associated protein (fap) genes in saliva samples from 50 patients with periodontitis and 51 healthy subjects.

Results

The incidence of both P. gingivalis and A. actinomycetemcomitans infections was higher (72% and 14%) in the “Periodontal disease” group than in the healthy subjects (P ​< ​0.001). The P. gingivalis 16 ​S rDNA, fimA, and prtC genes were detected in 43.56%, 61.36%, and 84.09% of saliva samples, respectively, while A. actinomycetemcomitans 16 ​S rDNA, lktA, and fap genes were detected in 6.93%, 71.43%, and 0%, respectively. P. gingivalis strains with the fimA+/prtC ​+ ​genotype were found in 61.11% and 25% of chronic periodontitis patients and healthy subjects, respectively. By comparison, A. actinomycetemcomitans strains with the lktA+ ​genotype were found in 71.43% of chronic periodontitis patients.

Conclusion

Infection with fimA+ and prtC+ ​P. gingivalis or lktA+ ​A. actinomycetemcomitans was correlated with periodontal disease occurrence in Saudi adults. Nevertheless, A. actinomycetemcomitans lktA and P. gingivalis fimA and prtC are closely linked to periodontal destruction, whereas A. actinomycetemcomitans fap is not.

Human is a host to billions of microbes and has developed sophisticated defense systems to stave off infections. Macrophages, which are at the forefront of innate immune protection against bacterial invaders, play a critical role in host responses to intracellular bacteria. At the same time, these phagocytes are prime targets for intracellular bacteria seeking to exploit host cells. Neisseria meningitidis belongs to a select group of bacterial pathogens with a sophisticated arsenal of virulence factors that can disrupt macrophage defense mechanisms or counter-balance the host's immunological defense mechanisms in order to ensure survival or expansion in a hostile environment. Worldwide, meningococci continues to play a significant role in the development of severe sepsis and meningitis. There is still much to learn about the tactics N. meningitidis uses to avoid immune response, such as mimicking host molecules, expression of virulence factor, capsule switching, and lipopolysaccharide phase changes. The macrophage evasion mechanisms of meningococcal present significant challenges for therapy and treatments. This review provides an overview of factors that meningococci utilize to manipulate macrophage immune responses and understand the asymptomatic and infection phases. Knowledge of the intricate web of host-pathogen interaction can help us find new target sites to devise effective therapeutics.

This current study is to identify the most appropriate dose against intra and extrahepatic toxic agents as well as hematosuppressive agent in rats. The animals were divided into six groups (n ​= ​10). Group 1 was placed on basal diet. Group II, III and IV were placed on a basal diets supplemented with 9.9%, 19.8% and 30%, respectively of MCF-ADSPC. Group V was placed on basal diet fed with unfermented Adasonia digitata seeds (UF-ADS) for 56 days. The results revealed 9.9% MCF-ADSPC as better dose to augment weight growth and total protein in rats. Similarly, MCF-ADSPC generated slight increase of WBC and centrophils count at lowest dose (9.9%) and highest dose (30%), respectively better than UF-ADS. The levels of PCV, RBC, haemoglobin, neutrophil, lymphocyte, eosinophils, basophils and monocytes showed no significant difference. Whereas, 19.8% MCF-ADSPC showed a better protection against hepatotoxicity, nephrotoxicity, intestinal mucosa, abnormal cholesterol level and splenomegaly in relation to 9.9%, 30% MCF-ADSPC and UF-ADS. Conclusively, MCF-ADSPC nutriment at 19.8% dose protected functional endpoints of intra and extrahepatic tissues than UF-ADS in a rat model.

Women of European Ancestry are more likely to harbor a Lactobacillus-dominated microbiome that supports healthy pregnancy progression compared to women of African descent who are more likely to experience preterm birth due to a diverse microbial profile. However, to date, many of these studies linking a diverse vaginal profile to adverse pregnancy outcomes in women of African ancestry are commonly focused on Blacks in Westernized populations. To bridge this gap, a comparative systematic review and meta-analysis were performed by searching PubMed, Web of Science, EMBASE, and Cochrane Library databases. A total of 40 studies assessing the vaginal microbiome and preterm birth using molecular-based techniques were selected for full-text review. After extensively analyzing these studies for experimental design, the method applied, clinical characteristics, and geographical location, only two articles fulfilled the inclusion criteria for meta-analysis. A meta-analysis was conducted by merging two studies comprising 217 samples from 115 pregnant women of African descent. Taxon analysis of vaginal profiles shows that Nigerian women had a significantly higher abundance of Atopobium (q<0.05; permutation test), compared to African American (AA) women who were significantly more enriched with Sneathia (q<0.05; permutation test). The mean Alpha-diversity was not significantly different between the AA and Nigerian groups (3.3 ​± ​0.09 versus 2.9 ​± ​0.09, p ​= ​0.10) respectively. Vaginal communities of AA women were relatively unstable, only Ureaplasma parvum remained stable throughout pregnancy (p_ADF <0.001), whereas L. crispatus, L. iners, and Atopobium vaginae were relatively more stable over pregnancy (p_ADF <0.001) in Nigerian women. In summary, our study indicated that there are differences in the core vaginal microbiome composition in women of similar ethnicity in different geographical locations. Future work should focus on advancing precision medicine by understanding the microbiome from an individual perspective, independent of ethnicity.

Influenza is an age-old disease. With its pandemic spread over various centuries, the virus remains one of the most challenging ones in the environment. Its fast-changing genome, RNA, is highly dynamic, and new variants of all the strains are discovered each year. Influenza A remains the most prevalent strain to infect the human race. With its fast multiplication rate, a sudden spike in hospitalization and high demand for antiviral drugs is seen during flu seasons. Antiviral drugs are considered the most suitable and specific since they attack particular steps of viral replication and halt it. Amantadine and Rimantadine were quite successful in their time, but the discovery of resistant strains of the virus limited humans from using it as a potent drug. Against all odds, the duo still provides a lot of information to learn from and implement in the field of research and also forms a base for discovering or formulating a more potent and long-lasting drug. Even though people rely more on vaccines, it is because of these drugs that any unprecedented situations, even in the vaccinated individuals, can be prevented and the lives of numerous patients can be saved. Amongst all the drugs, Baloxavir marboxil, Zanamivir, and Peramivir are preferred by most health systems because of their recent discovery, highly specific nature, and even high bioavailability. Parallel to antiviral drugs, nanotechnology is emerging as a new alternative for the treatment of Influenza.

The biofilm is a bacterial colony wrapped in an auto-produced polymer matrix of polysaccharides, proteins, and DNA. Bacterial biofilms cause persistent infections because they are more resistant to antibiotics, disinfectants, and the immune system of the body. Other significant biofilm characteristics are a gradient of oxygen and nutrition from the top layer to the bottom layer of biofilms. Lower bacterial cell metabolic activity and longer doubling rates are linked to the gradients; these are the quiescent cells responsible for some of the resistance to antibiotics. Biofilms may be avoided and cured with vigorous antibiotic prophylaxis or treatment early on and with continuous suppressive medication. This review discusses the development of antibiotic resistance and tolerance in bacteria due to biofilm formation, the tolerance mechanisms, and the development of persistent cells that induce antibiotic resistance in bacteria. Recent strategies to combat antibiotic resistance are also discussed.

Background

Microbiomes have been identified in various tumor types and could affect tumor progression and treatment. As the most prevalent primary malignant eye tumor in adults, uveal melanoma (UM) has not been explored regarding its endogenous microbiome. Plaque radiotherapy (PRT) is the gold standard for the treatment of UM. Hereby, we recruited 71 UM patients, sequenced the 16S rRNA gene of their tumor tissues, and analyzed the association between UM microbiome and disease phenotypes.

Results

Clear bacterial signals were observed in UM tissues using fluorescence in situ hybridization. 450 bacterial species passed strict decontamination against 58 environmental control samples in 16S rRNA gene analysis, and these species formed three distinct types by unsupervised clustering. The UM microbiome types were significantly associated with PRT. A biomarker analysis showed that Pseudomonas was significantly enriched in the radiation group (RG) compared to the non-radiation group (NRG). A kind of radiation-resistant bacteria had a significantly higher positive rate in tumor tissues that underwent radiotherapy. We found that the radio-resistant bacteria Deinococcus was associated with smaller and earlier tumor stages, while Pseudomonas and Stenotrophomonas were associated with later metastasis.

Conclusion

An endogenous microbiome might exist in UM tissues and was associated with UM features and treatment. Whether the tumor-residing microbiome has a role in UM development and metastasis is worth further investigation.

Bacterial vaginosis (BV) is a polymicrobial vaginal dysbiosis alongside lactobacillus depletion that primarily affects women of reproductive age. The fishy odor vaginal discharge is the major cause of anaerobic pathogenic bacteria colonization. Symptomatic women face specific catastrophic physiological and immunopathological consequences in addition to an elevated risk of sexually transmitted infections. Further, rash antibiotic therapy has witnessed antimicrobial-resistance amplifying vaginal infections. The emergence of biofilm-associated antimicrobial-resistance has made the issue worsened. This article has gone on to explore novel regimens, advanced diagnosis, and various cutting-edge strategies that are found to be effective in addressing these problems and restoring vaginal health.