scholarly journals Diallyl Disulfide (DADS) Ameliorates Intestinal Candida albicans Infection by Modulating the Gut microbiota and Metabolites and Providing Intestinal Protection in Mice

2022 ◽  
Vol 11 ◽  
Author(s):  
Wanchao Hu ◽  
Liou Huang ◽  
Ziyang Zhou ◽  
Liping Yin ◽  
Jianguo Tang
Keyword(s):  
Arachidonic Acid ◽  
Candida Albicans ◽  
Gut Microbiota ◽  
Pathogenic Bacteria ◽  
Biological Activities ◽  
The Body ◽  
Rrna Gene ◽  
Diallyl Disulfide

Diallyl disulfide (DADS), a garlic extract also known as allicin, has been reported to have numerous biological activities, including anticancer, antifungal, and inflammation-inhibiting activities, among others. Although many studies have assessed whether DADS can treat Candida albicans infection in vitro, its in vivo function and the underlying mechanism are still not clear. Accumulated evidence has implicated the gut microbiota as an important factor in the colonization and invasion of C. albicans. Thus, this study aimed to identify the mechanism by which DADS ameliorates dextran sulfate (DSS)-induced intestinal C. albicans infection based on the systematic analysis of the gut microbiota and metabolomics in mice. Here, we determined the body weight, survival, colon length, histological score, and inflammatory cytokine levels in the serum and intestines of experimental mice. Fecal samples were collected for gut microbiota and metabolite analysis by 16S rRNA gene sequencing and LC–MS metabolomics, respectively. DADS significantly alleviated DSS-induced intestinal C. albicans infection and altered the gut microbial community structure and metabolic profile in the mice. The abundances of some pathogenic bacteria, such as Proteobacteria, Escherichia–Shigella, and Streptococcus, were notably decreased after treatment with DADS. In contrast, SCFA-producing bacteria, namely, Ruminiclostridium, Oscillibacter, and Ruminococcaceae_UCG−013, greatly increased in number. The perturbance of metabolites in infectious mice was improved by DADS, with increases in secondary bile acids, arachidonic acid, indoles and their derivatives, which were highly related to the multiple differentially altered metabolic pathways, namely, bile secretion, arachidonic acid metabolism, and tryptophan metabolism. This study indicated that DADS could modulate gut microbiota and metabolites and protect the gut barrier to alleviate DSS-induced intestinal C. albicans infection in mice. Moreover, this work might also provide novel insight into the treatment of C. albicans infection using DADS.

scholarly journals Anti-adipogenic and anti-obesity activities of purpurin in 3T3-L1 preadipocyte cells and in mice fed a high-fat diet

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Woo Nam ◽  
Seok Hyun Nam ◽  
Sung Phil Kim ◽  
Carol Levin ◽  
Mendel Friedman
Keyword(s):  
Weight Gain ◽  
High Fat Diet ◽  
Biological Activities ◽  
The Body ◽  
High Fat ◽  
In Vivo Models ◽  
Triglyceride Accumulation ◽  
In Cells

Abstract Background The body responds to overnutrition by converting stem cells to adipocytes. In vitro and in vivo studies have shown polyphenols and other natural compounds to be anti-adipogenic, presumably due in part to their antioxidant properties. Purpurin is a highly antioxidative anthraquinone and previous studies on anthraquinones have reported numerous biological activities in cells and animals. Anthraquinones have also been used to stimulate osteoblast differentiation, an inversely-related process to that of adipocyte differentiation. We propose that due to its high antioxidative properties, purpurin administration might attenuate adipogenesis in cells and in mice. Methods Our study will test the effect purpurin has on adipogenesis using both in vitro and in vivo models. The in vitro model consists of tracking with various biomarkers, the differentiation of pre-adipocyte to adipocytes in cell culture. The compound will then be tested in mice fed a high-fat diet. Murine 3T3-L1 preadipocyte cells were stimulated to differentiate in the presence or absence of purpurin. The following cellular parameters were measured: intracellular reactive oxygen species (ROS), membrane potential of the mitochondria, ATP production, activation of AMPK (adenosine 5′-monophosphate-activated protein kinase), insulin-induced lipid accumulation, triglyceride accumulation, and expression of PPARγ (peroxisome proliferator activated receptor-γ) and C/EBPα (CCAAT enhancer binding protein α). In vivo, mice were fed high fat diets supplemented with various levels of purpurin. Data collected from the animals included anthropometric data, glucose tolerance test results, and postmortem plasma glucose, lipid levels, and organ examinations. Results The administration of purpurin at 50 and 100 μM in 3T3-L1 cells, and at 40 and 80 mg/kg in mice proved to be a sensitive range: the lower concentrations affected several measured parameters, whereas at the higher doses purpurin consistently mitigated biomarkers associated with adipogenesis, and weight gain in mice. Purpurin appears to be an effective antiadipogenic compound. Conclusion The anthraquinone purpurin has potent in vitro anti-adipogenic effects in cells and in vivo anti-obesity effects in mice consuming a high-fat diet. Differentiation of 3T3-L1 cells was dose-dependently inhibited by purpurin, apparently by AMPK activation. Mice on a high-fat diet experienced a dose-dependent reduction in induced weight gain of up to 55%.

The molecular biology of mammalian arachidonic acid metabolism

1991 ◽  
Vol 260 (2) ◽  
pp. L13-L28 ◽  
Author(s):  
E. Sigal
Keyword(s):  
Arachidonic Acid ◽  
Acid Metabolism ◽  
Recombinant Dna ◽  
Biological Activities ◽  
Biological Effects ◽  
Arachidonic Acid Metabolism ◽  
Bioactive Metabolites ◽  
Wide Range

The metabolism of arachidonic acid by cyclooxygenase and lipoxygenase enzymes results in a wide range of oxidized products with potent biological activities. These metabolites, which include the prostaglandins and leukotrienes, have been implicated in the pathogenesis of a variety of inflammatory diseases. Research over the last decade has focused primarily on the elucidation of the chemical structure of the metabolites and their biological effects in vitro and in vivo. Recently, research on the enzymes that produce these bioactive metabolites through oxidization of arachidonic acid has intensified. Recombinant DNA techniques have enabled investigators to determine the nucleotide sequences for several of the enzymes in the arachidonic acid cascade. The resulting cDNAs are now being used to further investigate the biochemical and biological features of arachidonic acid metabolism. The purpose of this paper is to review how the cDNAs for these enzymes were obtained, what information they convey, and how they are being applied in current research.

scholarly journals In Vitro and In Vivo Anti-infective Potential of Thymol Against Early Childhood Caries Causing Dual Species Candida albicans and Streptococcus mutans

2021 ◽  
Vol 12 ◽  
Author(s):  
Arumugam Priya ◽  
Anthonymuthu Selvaraj ◽  
Dass Divya ◽  
Ramalingam Karthik Raja ◽  
Shunmugiah Karutha Pandian
Keyword(s):  
Early Childhood ◽  
Candida Albicans ◽  
Streptococcus Mutans ◽  
Early Childhood Caries ◽  
Galleria Mellonella ◽  
Biological Activities ◽  
Infective Potential ◽  
Childhood Caries

Early childhood caries (ECC), a severe form of caries due to cross-kingdom interaction of Candida albicans and Streptococcus mutans, is a serious childhood dental disease that affects majority of the children with poor background. The present study investigated the anti-infective potential of thymol against C. albicans and S. mutans dual species for the management of ECC. Thymol, a plant derivative of the monoterpene group, has been well known for its numerous biological activities. Thymol at 300 μg/ml concentration completely arrested growth and proliferation of dual species of C. albicans and S. mutans. Rapid killing efficacy of pathogens, within a span of 2 min, was observed in the time kill assay. In addition, at sub-inhibitory concentrations, thymol effectively diminished the biofilm formation and virulence of both C. albicans and S. mutans such as yeast-to-hyphal transition, hyphal-to-yeast transition, filamentation, and acidogenicity and acidurity, respectively, in single and dual species state. qPCR analysis was consistent with virulence assays. Also, through the invertebrate model system Galleria mellonella, in vivo toxicity and efficacy of the phytocompound was assessed, and it was found that no significant toxic effect was observed. Moreover, thymol was found to be proficient in diminishing the infection under single and dual state in in vivo condition. Overall, the results from the present study illustrate the anti-infective potential of thymol against the ECC-causing dual species, C. albicans and S. mutans, and the applicability of thymol in medicated dentifrice formulation.

scholarly journals Lactobacillus gallinarum modulates the gut microbiota and produces anti-cancer metabolites to protect against colorectal tumourigenesis

Gut ◽  
2021 ◽  
pp. gutjnl-2020-323951
Author(s):  
Naoki Sugimura ◽  
Qing Li ◽  
Eagle Siu Hong Chu ◽  
Harry Cheuk Hay Lau ◽  
Winnie Fong ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Cell Proliferation ◽  
Gut Microbiota ◽  
Pathogenic Bacteria ◽  
Culture Supernatant ◽  
Suppressive Effect ◽  
Cell Cycle Distribution ◽  
Metagenomic Sequencing

ObjectiveUsing faecal shotgun metagenomic sequencing, we identified the depletion of Lactobacillus gallinarum in patients with colorectal cancer (CRC). We aimed to determine the potential antitumourigenic role of L. gallinarum in colorectal tumourigenesis.DesignThe tumor-suppressive effect of L. gallinarum was assessed in murine models of CRC. CRC cell lines and organoids derived from patients with CRC were cultured with L. gallinarum or Escherichia coli MG1655 culture-supernatant to evaluate cell proliferation, apoptosis and cell cycle distribution. Gut microbiota was assessed by 16S ribosomal DNA sequencing. Antitumour molecule produced from L. gallinarum was identified by liquid chromatography mass spectrometry (LC-MS/MS) and targeted mass spectrometry.ResultsL. gallinarum significantly reduced intestinal tumour number and size compared with E. coli MG1655 and phosphate-buffered saline in both male and female murine intestinal tumourigenesis models. Faecal microbial profiling revealed enrichment of probiotics and depletion of pathogenic bacteria in L. gallinarum-treated mice. Culturing CRC cells with L. gallinarum culture-supernatant (5%, 10% and 20%) concentration-dependently suppressed cell proliferation and colony formation. L. gallinarum culture-supernatant significantly promoted apoptosis in CRC cells and patient-derived CRC organoids, but not in normal colon epithelial cells. Only L. gallinarum culture-supernatant with fraction size <3 kDa suppressed proliferation in CRC cells. Using LC-MS/MS, enrichments of indole-3-lactic acid (ILA) was identified in both L. gallinarum culture-supernatant and the gut of L. gallinarum-treated mice. ILA displayed anti-CRC growth in vitro and inhibited intestinal tumourigenesis in vivo.ConclusionL. gallinarum protects against intestinal tumourigenesis by producing protective metabolites that can promote apoptosis of CRC cells.

scholarly journals Intake of nanoparticles and impact on gut microbiota: in vitro and animal models available for testing

2021 ◽  
Vol 3 ◽  
Author(s):  
Débora Campos ◽  
Ricardo Goméz-García ◽  
Diana Oliveira ◽  
Ana Raquel Madureira
Keyword(s):  
Gut Microbiota ◽  
Oral Delivery ◽  
Animal Studies ◽  
Pathogenic Bacteria ◽  
Oral Intake ◽  
Nanosized Materials ◽  
Antimicrobial Nanoparticles ◽  
The Impact

ABSTRACT The oral delivery of compounds associated with diet or medication have an impact on the gut microbiota balance, which in turn, influences the physiologic process. Several reports have shown significant advances in clarifying the impact, interactions and outcomes of oral intake of nanoparticles and the human gut. These interactions may affect the bioavailability of the delivered compounds. In addition, there is a considerable breakthrough in the development of antimicrobial nanoparticles for intestinal pathogenic bacteria. Several in vitro fermentation and in vivo models have been developed throughout the years and were used to test these systems. The methodologies and studies carried out so far on the modulation of human and animal gut microbiome by oral delivery nanosized materials were reviewed. Overall, the available in vitro studies mimic the real physiological events enabling to select the best production conditions of nanoparticulate systems in a preliminary stage of research. On the other hand, animal studies can be used to access the dosage effect, safety and correlation between haematological, biochemical and symptoms, with gut microbiota groups and metabolites.

scholarly journals Human gut bifidobacteria inhibit the growth of the opportunistic fungal pathogen Candida albicans

2021 ◽  
Author(s):  
Liviana Ricci ◽  
Joanna Mackie ◽  
Gillian E Donachie ◽  
Ambre Chapuis ◽  
Kristyna Mezerova ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Inhibitory Activity ◽  
Fungal Pathogen ◽  
Antagonistic Activity ◽  
Rrna Gene ◽  
Human Gut ◽  
Bifidobacterium Adolescentis ◽  
Opportunistic Fungal Pathogen

The human gut microbiota protects the host from invading pathogens and the overgrowth of indigenous opportunistic species via mechanisms such as competition for nutrients and by production of antimicrobial compounds. Here, we investigated the antagonist activity of human gut bacteria towards Candida albicans, an opportunistic fungal pathogen that can cause severe infections and mortality in susceptible patients. Co-culture batch incubations of C. albicans in the presence of faecal microbiota from six different healthy individuals revealed varying levels of inhibitory activity against C. albicans. 16S rRNA gene sequence profiling of these faecal co-culture bacterial communities showed that the Bifidobacteriaceae family, and Bifidobacterium adolescentis in particular, were most correlated with antagonistic activity against C. albicans. Follow up mechanistic studies confirmed that culture supernatants of Bifidobacterium species, particularly B. adolescentis, inhibited C. albicans in vitro under both aerobic and anaerobic conditions. Production of the fermentation acids acetate and lactate, together with the concomitant decrease in pH, were strong drivers of the inhibitory activity. Bifidobacteria may therefore represent attractive targets for the development of probiotics and prebiotic interventions tailored to enhance inhibitory activity against C. albicans in vivo.

scholarly journals Candida albicans and Pseudomonas aeruginosa Interact To Enhance Virulence of Mucosal Infection in Transparent Zebrafish

2017 ◽  
Vol 85 (11) ◽  
Author(s):  
Audrey C. Bergeron ◽  
Brittany G. Seman ◽  
John H. Hammond ◽  
Linda S. Archambault ◽  
Deborah A. Hogan ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Candida Albicans ◽  
The Body ◽  
Host Responses ◽  
Patient Treatment ◽  
Infection Model ◽  
Content Type ◽  
Epithelial Invasion

ABSTRACT Polymicrobial infections often include both fungi and bacteria and can complicate patient treatment and resolution of infection. Cross-kingdom interactions among bacteria, fungi, and/or the immune system during infection can enhance or block virulence mechanisms and influence disease progression. The fungus Candida albicans and the bacterium Pseudomonas aeruginosa are coisolated in the context of polymicrobial infection at a variety of sites throughout the body, including mucosal tissues such as the lung. In vitro, C. albicans and P. aeruginosa have a bidirectional and largely antagonistic relationship. Their interactions in vivo remain poorly understood, specifically regarding host responses in mediating infection. In this study, we examine trikingdom interactions using a transparent juvenile zebrafish to model mucosal lung infection and show that C. albicans and P. aeruginosa are synergistically virulent. We find that high C. albicans burden, fungal epithelial invasion, swimbladder edema, and epithelial extrusion events serve as predictive factors for mortality in our infection model. Longitudinal analyses of fungal, bacterial, and immune dynamics during coinfection suggest that enhanced morbidity is associated with exacerbated C. albicans pathogenesis and elevated inflammation. The P. aeruginosa quorum-sensing-deficient ΔlasR mutant also enhances C. albicans pathogenicity in coinfection and induces extrusion of the swimbladder. Together, these observations suggest that C. albicans-P. aeruginosa cross talk in vivo can benefit both organisms to the detriment of the host.

BIOLOGICAL ACTIVITIES OF HAMYCIN

1966 ◽  
Vol 12 (2) ◽  
pp. 377-384
Author(s):  
A. C. Maniar ◽  
Sarala Mavdikar
Keyword(s):  
Candida Albicans ◽  
Antifungal Activity ◽  
Oral Dose ◽  
Biological Activities ◽  
The Body ◽  
In Vitro Activity ◽  
Body Tissues ◽  
High Concentrations ◽  
Albumin Molecule

After ad ministration of an oral dose to mice, hamycin, an antifungal antibiotic, penetrated the body tissues and eliminated Cryptococcus neoformans present in the lungs. Out of 11 polyenes (hamycin, aureofungin, trichomycin, etruscomycin, amphotericin B, pimaricin, mycostatin, candidin, candicidin, PA150, and filipin), hamycin and aureofungin showed the highest "in vitro" activity against Candida albicans. The antifungal activity of hamycin, PA150, and aureofungin was increased by the addition of serum, plasma, or crystalline albumins. This increase in activity can be used as an additional characteristic to differentiate some of the polyenes. We now believe that serum was responsible for our previous findings that "high concentrations of hamycin in the organs of mice were detected". It has been shown that the complete albumin molecule was required to increase the activity of hamycin. The possibility that serum globulins or other proteins may increase the hamycin activity is not ruled out by our experiments.

scholarly journals Application of nano-curcumin as a natural antimicrobial agent against Gram-positive pathogens

2021 ◽  
Vol 13 (1) ◽  
pp. 110-126
Author(s):  
Ruchi Sankhwar ◽  
Shilpi Yadav ◽  
Abhishek Kumar ◽  
Ravi Kr. Gupta
Keyword(s):  
Pathogenic Bacteria ◽  
Biological Activities ◽  
Aqueous Solubility ◽  
Gram Positive ◽  
Curcumin Nanoparticles ◽  
Superficial Skin ◽  
Potential Applications ◽  
Conventional Antibiotics

Gram-positive bacteria cause various diseases from the superficial skin to deep tissue infections. The capability of causing numerous diseases is due to the production of virulence factors which are tightly regulated by the virulence genes. Various Gram-positive pathogenic bacteria e.g. Staphylococcus, Mycobacterium, and Listeria are capable of causing lethal infections in humans and animals. Conventional antibiotics, targeted antibiotics, and combinatorial drugs are used as therapeutic agents against Gram-positive pathogens. Due to intricate virulence pathway bacteria readily adopt resistance to available drugs. Therefore, there is need to develop some alternative approaches to combat these infections. Various natural extracts are effective against pathogenic bacteria with or without the available drugs. Curcumin is a natural extract of Curcuma longas rhizome, known as turmeric. Curcumin shows various biological activities such as antimicrobial, antioxidant and anti-inflammatory. It also shows strong antibacterial activity against Gram-positive and few Gram-negative bacteria. Besides all these beneficial applications, major drawbacks of curcumin are poor aqueous solubility and less bioavailability. However, drug delivery approaches including nanoformulation are developed to increase its stability in vitro and in vivo settings. The present review article focused on the translation of potential applications of curcumin in various diseases specifically caused by Gram-positive pathogens. Various methods used for the formulations of curcumin nanoparticles, combinatorial strategies with curcumin nanoparticles and their application in the prevention of infections have been discussed. The present article also discusses the future aspects of curcumin-nanoparticles and its use as an alternative therapeutic approach against pathogens.

Role of Modified Diet and Gut Microbiota in Metabolic Endotoxemia in Mice

2021 ◽  
Author(s):  
Iram Liaqat ◽  
Arjumand Iqbal Durrani ◽  
Urooj Zafar ◽  
Saima Rubab ◽  
Mehwish Faheem ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
16S Rrna Gene Sequencing ◽  
Diet Group ◽  
The Body ◽  
Chow Diet ◽  
Rrna Gene ◽  
Group 2 ◽  
Rrna Gene Sequencing ◽  
Metabolic Endotoxemia

Abstract This study was aimed to investigate the effect of cultured gut microbiota (GM) from obese humans coupled HFD in inducing metabolic endotoxemia in humanized mice. In total, 30 strains were isolated from 10 stool samples of obese patients. Following morphological and biochemical characterization, 16S rRNA gene sequencing of six abundant isolates identified these as Klebsiella aerogenes, Levilactobacillus brevis, Escherichia coli, Staphylococcus aureus, Bacillus cereus and Bacillus subtilis (MZ052089- MZ052094). In vivo trial using above six isolates, known as human gut microbiota (HGM), was performed for six months. Sixteen mice were distributed into four groups i.e., G1 (control) mice fed with chow diet, group 2 (G2) mice with HFD, group 3 (G3) mice with HFD + HGM and group 4 (G4) mice with chow diet + HGM. Body mass index (BMI) and plasma endotoxins were measured pre and post experiment. In vivo study revealed that HFD + HGM caused significant increase (3.9 g/cm at 20 weeks) in the body weight and BMI (0.4g/cm post experiment) of G3 mice compared to the other groups. One way ANOVA showed significantly higher level of endotoxins (2.41, 4.08 and 3.7 mmol/l) in mice groups G2, G3 and G4, respectively, indicating onset of metabolic endotoxemia. Cecal contents of experimental mice groups showed more diversified microbiota in mice groups G1 and G4 compared to G2 and G3 where high fat feeding alone and combined with obese gut microbiota caused a shift in microbial diversity as observed by all five strains belonging to either Firmicutes or Bacteriodetes phyla, respectively. In conclusion, current study reported that minor alteration in GM composition through HFD feeding and cultured GM transfer has significant impact in development of metabolic endotoxemia, possibly via modified intestinal permeability.

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