Specific Pathogenic Bacteria Research Articles

Antimicrobial effect of lactoferrin and glycerol monolaurate on selected bacteria associated with newborn infections

Human breast milk contains a rich array of bioactive substances, such as immunoglobulins, lactoferrin antimicrobial peptides, and glycerol monolaurate, which play a crucial role in providing immune protection to infants. Infant formula manufacturers strive to match mother's milk's nutritional makeup, including immune-boosting ingredients. Lactoferrin and glycerol monolaurate (GML) are important antibacterial compounds in human milk. The study aimed to investigate the effect of bovine lactoferrin (bLf) and GML in preventing the growth of inoculated bacteria into infant formula. The study examined both individual and combined use of these components. The bacteria that were tested included: 1) Gram-negative bacteria: Cronobacter sakazakii strains 12868 and 29004, Pseudomonas aeruginosa, Salmonella enterica Typhimurium, and 2) Gram-positive bacteria: Methicillin-resistant Staphylococcus aureus (MRSA), and Listeria monocytogenes. The result of the agar diffusion assays showed that bLf, at a concentration of 16 mg/disc, exhibited strong inhibition (≥20 mm) of all the selected bacterial strains. On the other hand, GML at a concentration of 8 mg/disc showed strong inhibition of all strains; however, Gram-positive bacteria were more susceptible, so a concentration of 5 mg/disc was enough to achieve strong inhibition of these strains. The minimal bactericidal concentrations (MBC) analysis aimed to achieve a >3-log reduction in the growth of various bacterial strains. The results showed that S. enterica Typhimurium and L. monocytogenes were more susceptible to bLf than the other strains (MBC: 7 and 4.8 mg/ml, respectively, vs. 14.9–18.4 mg/ml for the other strains). In contrast, MRSA and L. monocytogenes were more susceptible to GML (MBC: 6 and 10 mg/ml, respectively, vs. 16–18 mg/ml for Gram-negative strains). The results of reconstituted powdered infant formulas (RPIF), with the addition of bLf, GML, or both at pathogen-specific MBC, showed significant log reductions in the growth of experimentally inoculated bacteria compared to the control at different time intervals. All bacterial strains exposed to bLf and GML exhibited >3-log reduction within 72 h, with Gram-positive strains showing >7-log reduction. GML and bLf combined had a stronger anti-bacterial activity than individual components, indicating the potential of combining GML and bLf as natural agents against specific pathogenic bacteria. Future studies are needed to understand the potential use of these compounds in different food matrices and clinical settings.

Gut and respiratory microbiota landscapes in IgA nephropathy: a cross-sectional study

Background IgA nephropathy (IgAN) is intimately linked to mucosal immune responses, with nasopharyngeal and intestinal lymphoid tissues being crucial for its abnormal mucosal immunity. The specific pathogenic bacteria in these sites associated with IgAN, however, remain elusive. Our study employs 16S rRNA sequencing and machine learning (ML) approaches to identify specific pathogenic bacteria in these locations and to investigate common pathogens that may exacerbate IgAN. Methods In this cross-sectional analysis, we collected pharyngeal swabs and stool specimens from IgAN patients and healthy controls. We applied 16SrRNA sequencing to identify differential microbial populations. ML algorithms were then used to classify IgAN based on these microbial differences. Spearman correlation analysis was employed to link key bacteria with clinical parameters. Results We observed a reduced microbial diversity in IgAN patients compared to healthy controls. In the gut microbiota of IgAN patients, increases in Bacteroides, Escherichia-Shigella, and Parabacteroides, and decreases in Parasutterella, Dialister, Faecalibacterium, and Subdoligranulum were notable. In the respiratory microbiota, increases in Neisseria, Streptococcus, Fusobacterium, Porphyromonas, and Ralstonia, and decreases in Prevotella, Leptotrichia, and Veillonella were observed. Post-immunosuppressive therapy, Oxalobacter and Butyricoccus levels were significantly reduced in the gut, while Neisseria and Actinobacillus levels decreased in the respiratory tract. Veillonella and Fusobacterium appeared to influence IgAN through dual immune loci, with Fusobacterium abundance correlating with IgAN severity. Conclusions This study revealing that changes in flora structure could provide important pathological insights for identifying therapeutic targets, and ML could facilitate noninvasive diagnostic methods for IgAN.

Bioreceptor modified electrochemical biosensors for the detection of life threating pathogenic bacteria: a review.

The lack of reliable and efficient techniques for early monitoring to stop long-term effects on human health is an increasing problem as the pathogenesis effect of infectious bacteria is growing continuously. Therefore, developing an effective early detection technique coupled with efficient and continuous monitoring of pathogenic bacteria is increasingly becoming a global public health prime target. Electrochemical biosensors are among the strategies that can be utilized for accomplishing that goal with promising potential. In recent years, identifying target biological analytes by interacting with bioreceptors modified electrodes is among the most commonly used detection techniques in electrochemical biosensing strategies. The commonly employed bioreceptors are nucleic acid molecules (DNA or RNA), proteins, antibodies, enzymes, organisms, tissues, and biomimetic components such as molecularly imprinted polymers. Despite the advancement in electrochemical biosensing, developing a reliable and effective biosensor for detecting pathogenic bacteria is still in the infancy stage with so much room for growth. A major milestone in addressing some of the issues and improving the detection pathway is the investigation of specific bacterial detection techniques. The present study covers the fundamental concepts of electrochemical biosensors, human PB illnesses, and the latest electrochemical biosensors based on bioreceptor elements that are designed to detect specific pathogenic bacteria. This study aims to assist researchers with the most up-to-date research work in the field of bio-electrochemical pathogenic bacteria detection and monitoring.

Dysbiosis promotes recurrence of adenomatous polyps in the distal colorectum

BACKGROUND Colorectal polyps, which are characterized by a high recurrence rate, represent preneoplastic conditions of the intestine. Due to unclear mechanisms of pathogenesis, first-line therapies for non-hereditary recurrent colorectal polyps are limited to endoscopic resection. Although recent studies suggest a mechanistic link between intestinal dysbiosis and polyps, the exact compositions and roles of bacteria in the mucosa around the lesions, rather than feces, remain unsettled. AIM To clarify the composition and diversity of bacteria in the mucosa surrounding or 10 cm distal to recurrent intestinal polyps. METHODS Mucosal samples were collected from four patients consistently with adenomatous polyps (Ade), seven consistently with non-Ade (Pol), ten with current Pol but previous Ade, and six healthy individuals, and bacterial patterns were evaluated by 16S rDNA sequencing. Linear discriminant analysis and Student’s t -tests were used to identify the genus-level bacteria differences between groups with different colorectal polyp phenotypes. Pearson’s correlation coefficients were used to evaluate the correlation between intestinal bacteria at the genus level and clinical indicators. RESULTS The results confirmed a decreased level of probiotics and an enrichment of pathogenic bacteria in patients with all types of polyps compared to healthy individuals. These changes were not restricted to the mucosa within 0.5 cm adjacent to the polyps, but also existed in histologically normal tissue 10 cm distal from the lesions. Significant differences in bacterial diversity were observed in the mucosa from individuals with normal conditions, Pol, and Ade. Increased abundance of Gram-negative bacteria, including Klebsiella , Plesiomonas , and Cronobacter , was observed in Pol group and Ade group, suggesting that resistance to antibiotics may be one risk factor for bacterium-related harmful environment. Meanwhile, age and gender were linked to bacteria changes, indicating the potential involvement of sex hormones. CONCLUSION These preliminary results support intestinal dysbiosis as an important risk factor for recurrent polyps, especially adenoma. Targeting specific pathogenic bacteria may attenuate the recurrence of polyps.

Exploring Vernonia amygdalina’s leaf extracts for phytochemical screening and its anti-bacterial activities

ABSTRACT The aim of this study was to screen the phytochemicals and assess the antibacterial properties of crude extracts from Vernonia amygdalina leaves against specific pathogenic bacteria. Qualitative and qauntitave analysis was performed on both ethanol and ethyl acetate crude extracts using standardized techniques. The analysis revealed the presence of alkaloids, phenol, flavonoids, terpenoids, saponins, tannins, and cardiac glycosides in the ethanol extract, while saponins and glycosides were absent in the ethyl acetate extract. The quantities of phenols, flavonoids, and alkaloids were determined using Gallic acid, quercetin, and atropine assays, respectively. The ethanol extract contained 154.7 ± 3.6 (mg GAE/g) of total phenols, 33.3 ± 1.8 (mg QE/g) of flavonoids, and 2.4 ± 0.08 (mg AE) of alkaloids, whereas the ethyl acetate extract contained 93.7 ± 3.9 (mg GAE/g) of total phenols, 30.7 ± 8.3 (mg QE/g) of flavonoids, and 1.57 ± 0.3 (mg GAE/g) of alkaloids. This study identified 44 components in the ethanol crude extract and 10 components in the ethyl acetate crude extract. The presence of alkanes, alkenes, amines, carboxylic acids, and alcohols was confirmed by FT-IR analysis. Each crude extract was tested at concentrations of 500 mg/mL, 250 mg/mL, 125 mg/mL, and 62.5 mg/mL using the same method. A concentration of 0.001 mg/mL of Penicillin capsule standard drugs and dimethyl sulfoxide were used as positive and negative controls, respectively. Overall, the results of the study indicated that both crude extracts exhibited antibacterial activity at higher concentrations.

Luteolin exhibits antimicrobial actions against Salmonella Typhimurium and Escherichia coli: Impairment of cell adhesion, membrane integrity, and energy metabolism

There has been an increasing interest in phytochemicals with antimicrobial properties in food safety management. However, the mechanisms of action of phytochemicals remain mostly unknown, preventing their selective applications against biofilms of specific pathogenic bacteria. The objectives of the present study were to understand the antibiofilm and antibacterial properties of luteolin (LUT) and its modes of action against two detrimental foodborne pathogens, Salmonella enterica ser. Typhimurium and enterohemorrhagic Escherichia coli. The focus encompasses biofilm inhibition, interference with cell adhesion, disruption of membrane integrity, and dysfunctions of membrane-linked bacterial electron transport systems and energy metabolism. Our findings evidence that LUT prevents pathogenic biofilm formation on both biotic (eggshell) and abiotic (stainless steel and silicon rubber) surfaces by resisting irreversible cell adhesion and interfering with hydrophobic interactions between bacteria and contact surfaces. Our comprehensive biochemical and visual analyses further reveal that LUT mainly exhibits bactericidal activities by imposing oxidative stress on cells, leading to severe cellular structure damage, inhibition of metabolic and respiratory activities, and dysfunctions of energy metabolism, ultimately resulting in bacterial cell death. This study suggests that LUT has the potential to serve as a solution for developing effective, novel antimicrobials for improving food safety management.

Effects of Enterobacter cloacae insecticidal protein on the Duox-ROS system and midgut bacterial community and function of Galleria mellonella larvae

BackgroundEnterobacter cloacae insecticidal proteins have been reported to kill Galleria mellonella larvae through affecting their midgut microbiome. However, the mechanisms involved remain unclear. Here we aim to investigate how the insecticidal proteins act on the midgut Duox-ROS system and microbial community of G. mellonella larvae. MethodsReverse transcription qPCR and fluorescence probes were utilized to assess the Duox expression levels and to evaluate quantitative changes of the ROS levels. Sequencing of the 16S rRNA gene sequences of the midgut bacteria of G. mellonella larvae was conducted for further analyses of bacterial diversity, composition, and abundance. ResultsAfter the injection of the insecticidal proteins, the Duox expression levels first increased within 28 h, then dramatically peaked at 36 h, and slowly decreased thereafter. Simultaneously, the ROS levels increased significantly at 36 h, peaked at 48 h, and rapidly declined to the normal level at 60 h. Responsive to the change of the ROS levels, the structure of the midgut microbial community was altered substantially, compared to that of the untreated larvae. The relative abundance of Enterobacteriaceae and other specific pathogenic bacteria increased significantly, whereas that of Lactobacillus decreased sharply. Importantly, notable shifts were observed in the crucial midgut predicted metabolic functions, including membrane transportation, carbohydrate metabolism, and amino acid metabolism. ConclusionInsecticidal proteins of E. cloacae kill G. mellonella larvae mainly through generation of high oxidative stress, alterations of the midgut microbial community and function, and damage to the physiological functions. These findings provide insights into the inhibition mechanism of E. cloacae insecticidal proteins to G. mellonella larvae.

Overview of Opportunistic Bacteria

The receptive patient and the bacterium serve as the two defining criteria for opportunistic bacteria. Theoretically, no saprophytic or typical commensal microbes can infiltrate a healthy receptive person. Only specific "undesirable" commensal species, "such as Vargues' Specific Pathogenic Bacteria", can infect this person. Several species from the typical commensal flora, or opportunistic bacteria in the wide meaning of the word, “may infiltrate an otherwise healthy host if their immune defences temporarily deteriorate”. Even species that were previously thought to be non-virulent may assault an immunosuppressed patient with a significant and protracted immune system depression, “including various saprophytic and commensal microbes”. Several bacteria that are typically found in water, food, and the air have recently become opportunistic pathogens in both people and animals. The issue is made more difficult by the introduction of many antibiotic-resistant strains of these opportunistic pathogens, which make hospital-acquired infections in susceptible hosts challenging to treat in the setting of illness.

AI-2 quorum sensing signal disrupts coral symbiotic homeostasis and induces host bleaching

Symbiotic microorganisms play critical ecophysiological roles that facilitate the maintenance of coral health. Currently, information on the gene and protein pathways contributing to bleaching responses is lacking, including the role of autoinducers. Although the autoinducer AI-1 is well understood, information on AI-2 is insufficient. Here, we observed a 3.7–4.0 times higher abundance of the AI-2 synthesis gene luxS in bleached individuals relative to their healthy counterparts among reef-building coral samples from the natural environment. Laboratory tests further revealed that AI-2 contributed significantly to an increase in coral bleaching, altered the ratio of potential probiotic and pathogenic bacteria, and suppressed the antiviral activity of specific pathogenic bacteria while enhancing their functional potential, such as energy metabolism, chemotaxis, biofilm formation and virulence release. Structural equation modeling indicated that AI-2 influences the microbial composition, network structure, and pathogenic features, which collectively contribute to the coral bleaching status. Collectively, our results offer novel potential strategies for coral conservation based on a signal manipulation approach.

Pore-Forming Toxin-Driven Recovery of Peroxidase-Mimicking Activity in Biomass Channels for Label-Free Electrochemical Bacteria Sensing.

The development of sensitive, selective, and rapid methods to detect bacteria in complex media is essential to ensuring human health. Virulence factors, particularly pore-forming toxins (PFTs) secreted by pathogenic bacteria, play a crucial role in bacterial diseases and serve as indicators of disease severity. In this study, a nanochannel-based label-free electrochemical sensing platform was developed for the detection of specific pathogenic bacteria based on their secreted PFTs. In this design, wood substrate channels were functionalized with a Fe-based metal-organic framework (FeMOF) and then protected with a layer of phosphatidylcholine (PC)-based phospholipid membrane (PM) that serves as a peroxidase mimetic and a channel gatekeeper, respectively. Using Staphylococcus aureus (S. aureus) as the model bacteria, the PC-specific PFTs secreted by S. aureus perforate the PM layer. Now exposed to the FeMOF, uncharged 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonate) (ABTS) molecules in the electrolyte undergo oxidation to cationic products (ABTS•+). The measured transmembrane ionic current indicates the presence of S. aureus and methicillin-resistant S. aureus (MRSA) with a low detection limit of 3 cfu mL-1. Besides excellent specificity, this sensing approach exhibits satisfactory performance for the detection of target bacteria in the complex media of food.

Gut microbiota composition in patients with Crohn's disease in Saudi Arabia.

Crohn's disease (CD) entails intricate interactions with gut microbiome diversity, richness, and composition. The relationship between CD and gut microbiome is not clearly understood and has not been previously characterized in Saudi Arabia. We performed statistical analysis about various factors influencing CD activity and microbiota dysbiosis, including diagnosis, treatment, and its impact on their quality of life as well as high-throughput metagenomic V3-V4 16S rRNA encoding gene hypervariable region of a total of eighty patients with CD, both in its active and inactive state with healthy controls. The results were correlated with the demographic and lifestyle information, which the participants provided via a questionnaire. α-diversity measures indicated lower bacterial diversity and richness in the active and inactive CD groups compared to the control group. Greater dysbiosis was observed in the active CD patients compared to the inactive form of the disease, showed by a reduction in microbial diversity. Specific pathogenic bacteria such as Filifactor, Peptoniphilus, and Sellimonas were identified as characteristic of CD groups. In contrast, anti-inflammatory bacteria like Defluviitalea, Papillibacter, and Petroclostridium were associated with the control group. Among the various factors influencing disease activity and microbiota dysbiosis, smoking emerged as the most significant, with reduced α-diversity and richness for the smokers in all groups, and proinflammatory Fusobacteria was more present (p<0.05). Opposite to the control group, microbial diversity and richness were lower in CD participants of older age compared to younger ones, and male CD participants showed less diversity compared to women participants from the same groups. Our results describe the first report on the relationship between microbiota and Crohn's disease progress in Saudi Arabia, which may provide a theoretical basis for the application of therapeutic methods to regulate gut microbes in CD.

Ceftobiprole mono-therapy versus combination or non-combination regimen of standard antibiotics for the treatment of complicated infections: A systematic review and meta-analysis

ObjectiveVarious bacteria produce complicated infections that are difficult to treat worldwide. Ceftobiprole is effective against resistant Gram-positive and Gram-negative bacteria. MethodsThis review assessed effectiveness and safety of ceftobiprole monotherapy for severe infections. A systematic review and meta-analysis of randomized controlled trials comparing clinical cure, microbiological cure, and safety of ceftobiprole alone to a combination or non-combination antibiotic regimen was conducted. Until December 20, 2022, we searched a major databases. ResultsThis study includes 4168 patients from six trials. Ceftobiprole and comparator-received patients had similar clinical responses for all patient population. Also, the eradication rate of all organisms and specific pathogenic bacteria in microbiologically examined patients was comparable between the groups. Ceftobiprole induced more gastrointestinal side events than comparable drugs, mostly nausea [OR 1.91 (1.26-2.90), p=<0.01]. While skin-related adverse events were significantly associated with comparator antibiotics [6 trials, 4062 patients; OR 0.77 (0.60-0.99), p=0.03]. Conclusion: Ceftobiprole monotherapy is effective and safe for severe infections caused by Gram-positive or Gram-negative bacteria.

Changes in fecal microbiota during estrous cycle in healthy thoroughbred mares

Gut microbiota plays a crucial role in various physiological processes, including the regulation of the reproductive system and steroid sex hormones. Throughout the normal estrous cycle of healthy mares, the levels of estradiol-17β (E2) and progesterone (P4) in the blood exhibit periodic changes. To investigate the relationship between cyclic changes in steroid sex hormones and the gut microbiome of mares, we analyzed the fecal microbiota composition in healthy mares during the typical estrous cycle. Blood and fecal samples from five healthy mares were collected, E2 and P4 levels in serum were analyzed using radioimmunoassay (RIA), and the gut microbiome was analyzed by 16S rRNA sequencing. The overall richness and composition of the gut microbiota remained relatively stable during the normal estrous cycle in mares. The Linear Discriminant Analysis Effect Size analysis of the microbial composition during the follicular and luteal phases identified the Rhodococcus genus as differentially abundant. These findings indicate that the mare's gut microbiota's significant composition remains consistent throughout the estrous cycle. At the same time, specific low-abundance pathogenic bacteria exhibit changes that align with sexual hormonal fluctuations.

Serovar-level identification of bacterial foodborne pathogens from full-length 16S rRNA gene sequencing.

The resolution of variation within species is critical for interpreting and acting on many microbial measurements. In the key foodborne pathogens Salmonella and Escherichia coli, the primary subspecies classification scheme used is serotyping: differentiating variants within these species by surface antigen profiles. Serotype prediction from whole-genome sequencing (WGS) of isolates is now seen as comparable or preferable to traditional laboratory methods where WGS is available. However, laboratory and WGS methods depend on an isolation step that is time-consuming and incompletely represents the sample when multiple strains are present. Community sequencing approaches that skip the isolation step are, therefore, of interest for pathogen surveillance. Here, we evaluated the viability of amplicon sequencing of the full-length 16S rRNA gene for serotyping Salmonella enterica and E. coli. We developed a novel algorithm for serotype prediction, implemented as an R package (Seroplacer), which takes as input full-length 16S rRNA gene sequences and outputs serovar predictions after phylogenetic placement into a reference phylogeny. We achieved over 89% accuracy in predicting Salmonella serotypes on in silico test data and identified key pathogenic serovars of Salmonella and E. coli in isolate and environmental test samples. Although serotype prediction from 16S rRNA gene sequences is not as accurate as serotype prediction from WGS of isolates, the potential to identify dangerous serovars directly from amplicon sequencing of environmental samples is intriguing for pathogen surveillance. The capabilities developed here are also broadly relevant to other applications where intraspecies variation and direct sequencing from environmental samples could be valuable.IMPORTANCEIn order to prevent and stop outbreaks of foodborne pathogens, it is important that we can detect when pathogenic bacteria are present in a food or food-associated site and identify connections between specific pathogenic bacteria present in different samples. In this work, we develop a new computational technology that allows the important foodborne pathogens Escherichia coli and Salmonella enterica to be serotyped (a subspecies level classification) from sequencing of a single-marker gene, and the 16S rRNA gene often used to surveil bacterial communities. Our results suggest current limitations to serotyping from 16S rRNA gene sequencing alone but set the stage for further progress that we consider likely given the rapid advance in the long-read sequencing technologies and genomic databases our work leverages. If this research direction succeeds, it could enable better detection of foodborne pathogens before they reach the public and speed the resolution of foodborne pathogen outbreaks.

The Association between the Gut Microbiota and Erectile Dysfunction.

Explore the causal relationship between the gut microbiota and erectile dysfunction (ED) at phylum, class, order, family, and genus levels, and identify specific pathogenic bacteria that may be associated with the onset and progression of ED. The genetic variation data of 196 human gut microbiota incorporated in our study came from the human gut microbiome Genome Wide Association Studies (GWAS) dataset released by the MiBioGen Consortium. The GWAS statistics for ED were extracted from one study by Bovijn et al., which included 223,805 participants of European ancestry, of whom 6,175 were diagnosed with ED. Subsequently, Mendelian randomization (MR) analysis was carried out to explore whether a causal relationship exists between the gut microbiota and ED. Additionally, bidirectional MR analysis was performed to examine the directionality of the causal relationship. Through MR analysis, we found that family Lachnospiraceae (odds ratio [OR]: 1.27, 95% confidence interval [CI]: 1.05-1.52, p=0.01) and its subclass genus LachnospiraceaeNC2004 group (OR: 1.17, 95% CI: 1.01-1.37, p=0.04) are associated with a higher risk of ED. In addition, genus Oscillibacter (OR: 1.17, 95% CI: 1.02-1.35, p=0.03), genus Senegalimassilia (OR: 1.32, 95% CI: 1.06-1.64, p=0.01) and genus Tyzzerella3 (OR: 1.14, 95% CI: 1.02-1.27, p=0.02) also increase the risk of ED. In contrast, the inverse variance weighted estimate of genus RuminococcaceaeUCG013 (OR: 0.77, 95% CI: 0.61-0.96, p=0.02) suggests that it has a protective effect against the occurrence of ED. This study preliminarily identified 6 bacterial taxa that may have a causal relationship with ED, including family Lachnospiraceae, genus Lachnospiraceae NC2004 group, Oscillibacter, Senegalimassilia, Tyzzerella 3 and Ruminococcaceae UCG013. These identified important bacterial taxa may serve as candidates for microbiome intervention in future ED clinical trials.

BIOGENIC NANOSCALE SILVER PARTICLES: A STUDY ON THEIR ANTIMICROBIAL POTENTIAL

A sustainable method for producing silver nanoparticles (AgNPs) using Vitis vinifera seed extract has been proposed. The formation of AgNPs was confirmed through spectroscopy, X-ray Diffraction (XRD), and electron microscopy. The UV-visible spectrophotometer revealed distinct absorbance peaks at 398.80 nm and 416.24 nm, signifying the presence of Surface Plasmon Resonance (SPR). XRD, quasi-elastic light scattering, and surface topography results exposed that the AgNPs were crystalline and had rod-like shapes. FTIR identified seed extract functional groups that reduced silver ions to AgNPs and acted as capping agents. The nanoparticles showed inhibition against gram-positive microorganisms like Staphylococcus pneumonia and Mycobacterium tuberculosis, surpassing their effectiveness against gram-negative microorganisms such as Pseudomonas fluorescens. This environmentally responsible approach not only offers a green synthesis method but also holds promise for combating specific pathogenic bacteria.

Fibroblast Growth Factor 19 Alters Bile Acids to Induce Dysbiosis in Mice With Alcohol-Induced Liver Disease

Excessive alcohol consumption can lead to alcohol-associated liver disease, a spectrum of conditions ranging from steatosis to fibrosis and cirrhosis. Bile acids regulate metabolic pathways by binding to cellular and nuclear receptors, and they also interact with the gut microbiome to control microbial overgrowth. Fibroblast growth factor 19 (FGF-19) is an ileum-derived hormone induced and released in response to bile acid activation of the nuclear receptor farnesoid X receptor. FGF-19 signaling is dysregulated with ethanol consumption and is increased in patients with alcoholic hepatitis. Here, we examined the effects of FGF-19 in a mouse model of chronic+ binge ethanol feeding. After injection of adeno-associated virus-green fluorescent protein or AAV-FGF-19, female C57BL/6J mice were pair-fed a Lieber DeCarli liquid diet (5% v/v) or control diet for 10 days and were given a bolus gavage of 5% ethanol or maltose control to represent a binge drinking episode. Tissues were collected for analysis 9 hours after the binge. Chronic+ binge ethanol feeding induced steatosis regardless of FGF-19 expression. Interestingly, FGF-19 and ethanol resulted in significantly increased liver inflammation, as measured by Il6, Tgfβ, and Tnfα, compared with ethanol alone. Both ethanol and FGF-19 decreased bile acid synthesis, and FGF-19 significantly reduced secondary bile acids, leading to overgrowth of specific pathogenic bacteria including Enterococcus faecalis, Escherichia coli, and Clostridium perfringens. Dysregulation of FGF-19 and consequent changes in bile acid synthesis and composition during alcohol consumption may be a contributing factor to alcohol-induced liver disease and dysbiosis.

Targeted Depletion of Individual Pathogen by Bacteria-Templated Polymer.

Selective and targeted removal of individual species or strains of bacteria from complex communities can be desirable over traditional and broadly acting antibiotics in several conditions. However, strategies that can detect and ablate bacteria with high specificity are emerging in recent years. Herein, a platform is reported that uses bacteria as a template to synthesize polymers containing guanidinium groups for self-selective depletion of specific pathogenic bacteria without disturbing microbial communities. Different from conventional antibiotics, repeated treatment of bacteria with the templated polymers does not evolve drug resistance mutants after 20 days of serial passaging. Especially, high in vivo therapeutic effectiveness of the templated polymers is achieved in E. coli- and P. aeruginosa-induced microbial peritonitis. The templated polymers have shown high selectivity in in vivo antimicrobial activity, which has excellent potential as systemic antimicrobials against bacterial infections.

Evaluation of the Effectiveness of Staphylococcus Phages in a Skincare Serum against Staphylococcus spp.

The emergence of multidrug-resistant (MDR) Staphylococcus spp. has resulted in the reduced use of antibiotics in many skincare cosmetic products. Alternative treatments using natural bioactive compounds and chemical agents can be replaced. However, these compounds have induced negative side effects among users and are not environmentally friendly. Phage therapy is an alternative to antibiotics for the treatment of specific pathogenic bacteria including Staphylococcus spp., without harmful effects on human skin cells and microflora. Phages can be potentially used in cosmetic products. The direct application of phage-based cosmetic products on skin can reduce the chance of skin infection caused by pathogenic Staphylococcus spp. In the present work, we isolated 17 Staphylococcus phages from sewage and soil samples. Phage A1 showed the highest lytic ability at 50% (B1 profile), covering 13 tested Staphylococcus isolates including Staphylococcus aureus (SA), methicillin-resistant S. aureus (MRSA), S. capitis (SC), and S. epidermidis (SE). Phage A1 reduced the representative S. aureus ATCC 25923 and S. capitis SC1 by 2.0 ± 0.1 and 4.1 ± 0.3 log units at a multiplicity of infection (MOI) of 104 and by 4.2 ± 0.2 and 4.4 ± 0.5 log units at a MOI of 105 after 6 h of post-phage treatment. The transmission electron microscope revealed that phage A1 was classified in the order Caudovirales of the family Myoviridae based on its appearance. Phage A1 showed optimal survival in the presence of a 0.125% (v/v) solidant DMH suspension after 3 h of post-treatment. Under a phage skincare serum formulation, the titers of phage A1 were reduced by 0.46 and 0.85 log units after storage at 4 and 25 °C, whereas a reduction of 2.96 log units was also observed after storage at 37° for 90 days. This study provides strong evidence for the effectiveness of phage application in cosmetic skincare serum for the treatment of skin diseases caused by MDR and pathogenic Staphylococcus spp. The concept of this study could be advantageous for cosmetic and/or cosmeceutical industries searching for new bioactive ingredients for cosmetic/cosmeceutical products.

Melatonin supplementation protects against traumatic colon injury by regulating SERPINA3N protein expression.

Traumatic colon injury (TCI) is a typical injury with high mortality. Prolongation of the intervention time window is a potentially useful approach to improving the outcomes of TCI casualties. This study aimed to identify the pathological mechanisms of TCI and to develop effective strategies to extend the survival time. A semicircular incision was made to prepare a TCI model using C57BL/6 mice. An overview of microbiota dysregulation was achieved by metagenome sequencing. Protein expression reprogramming in the intestinal epithelium was investigated using proteomics profiling. The mice that were subjected to TCI died within a short period of time when not treated. Gut symbiosis showed abrupt turbulence, and specific pathogenic bacteria rapidly proliferated. The protein expression in the intestinal epithelium was also reprogrammed. Among the differentially expressed proteins, SERPINA3N was overexpressed after TCI modeling. Deletion of Serpina3n prolonged the posttraumatic survival time of mice with TCI by improving gut homeostasis in vivo. To promote the translational application of this research, the effects of melatonin (MLT), an oral inhibitor of the SERPINA3N protein, were further investigated. MLT effectively downregulated SERPINA3N expression and mitigated TCI-induced death by suppressing the NF-κB signaling pathway. Our findings prove that preventive administration of MLT serves as an effective regimen to prolong the posttraumatic survival time by restoring gut homeostasis perturbed by TCI. It may become a novel strategy for improving the prognosis of patients suffering from TCI.