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IMPORTANCE: Even though studying on the possible involvement of extracellular vesicles (EVs) in host-microbe interactions, how these relationships mediate host physiology has not clarified yet. Our current findings provide insights into the encouraging benefits of dietary source-derived EVs and microRNAs (miRNAs) on organic acid production and ultimately stimulating gut microbiome for human health, suggesting that supplementation of dietary colostrum EVs and miRNAs is a novel preventive strategy for the treatment of inflammatory bowel disease.
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Colite , Vesículas Extracelulares , MicroRNAs , Feminino , Gravidez , Humanos , Animais , Bovinos , MicroRNAs/genética , Ácido 3-Hidroxibutírico , Akkermansia , Colostro , Colite/induzido quimicamenteRESUMO
Sepsis is a life-threatening condition with systemic inflammatory responses caused by bacterial infections. Considering the emergence of antibiotic-resistant bacteria such as methicillin-resistant Staphylococcus aureus (MRSA), sepsis is a great threat to public health. The gold standard methods for antimicrobial susceptibility testing (AST), however, take at least approximately 3 days to implement the entire blood culture, pure culture, and AST processes. To overcome the time-consuming nature of conventional AST, a method employing a chromatic biosensor composed of poly(diacetylene), alginate, and LB broth (PAL) is introduced in this study. Compared to the gold standards, AST with PAL biosensors can be completed within a time frame as short as 16 h. Such a significant reduction in time is possible because the consecutive cultures and AST are carried out simultaneously by encapsulating the bacterial nutrients and detection molecules into a single component. The bead-like hydrogel sensors were used in their freeze-dried form, which endows them with portability and stability, thus making them adequate for point-of-care testing. The PAL biosensor yields minimum inhibitory concentrations comparable to those from the Clinical and Laboratory Standards Institute, and the applicability of the biosensor is further shown in MRSA-infected mice.
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Staphylococcus aureus Resistente à Meticilina , Sepse , Animais , Camundongos , Sistemas Automatizados de Assistência Junto ao Leito , Colorimetria , Hidrogéis , Antibacterianos/farmacologia , Bactérias , Testes ImediatosRESUMO
SCOPE: Mild cognitive impairment is associated with a high prevalence of dementia. The study examines the benefits of a modified Korean MIND (K-MIND) diet and explores biomarkers using multi-omics analysis. METHODS AND RESULTS: The K-MIND diet, tailored to the elderly Korean population, includes perilla oil, milk, or fermented milk, and avoids alcohol consumption. As a result, the K-MIND diet significantly improves subjects "orientation to place" in the Korean version of the Mini-Mental State Examination, 2nd edition test. According to multi-omics analysis, the K-MIND diet upregulates genes associated with mitochondrial respiration, including ubiquinone oxidoreductase, cytochrome C oxidase, and ATP synthase, and immune system processes, and downregulates genes related to nuclear factor kappa B activity and inflammatory responses. In addition, K-MIND affects the metabolic pathways of glycine, serine, threonine, tryptophan, and sphingolipids, which are closely linked to cognitive function through synthesis of neurotransmitters and structures of brain cell membranes. CONCLUSION: The findings imply that the K-MIND diet improves cognitive function by upregulating key genes involved in oxidative phosphorylation and downregulating pro-inflammatory cytokines.
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Aminoácidos , Cognição , Humanos , Feminino , Idoso , Dieta , Inflamação , República da CoreiaRESUMO
Korean red ginseng has been widely used as an herbal medicine. Red ginseng dietary fiber (RGDF) is a residue of the processed ginseng product but still contains bioactive constituents that can be applied as prebiotics. In this study, we evaluated changes on fermentation profiles and probiotic properties of strains that belong to family Lactobacillaceae with RGDF supplementation. Metabolomic analyses were performed to understand specific mechanisms on the metabolic alteration by RGDF and to discover novel bioactive compounds secreted by the RGDF-supplemented probiotic strain. RGDF supplementation promoted short-chain fatty acid (SCFA) production, carbon source utilization, and gut epithelial adhesion of Lactiplantibacillus plantarum and inhibited attachment of enteropathogens. Intracellular and extracellular metabolome analyses revealed that RGDF induced metabolic alteration, especially associated with central carbon metabolism, and produced RGDF-specific metabolites secreted by L. plantarum, respectively. Specifically, L. plantarum showed decreases in intracellular metabolites of oleic acid, nicotinic acid, uracil, and glyceric acid, while extracellular secretion of several metabolites including oleic acid, 2-hydroxybutanoic acid, hexanol, and butyl acetate increased. RGDF supplementation had distinct effects on L. plantarum metabolism compared with fructooligosaccharide supplementation. These findings present potential applications of RGDF as prebiotics and bioactive compounds produced by RGDF-supplemented L. plantarum as novel postbiotic metabolites for human disease prevention and treatment.
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Melanogenesis is responsible for skin pigmentation and the enzymatic browning of foods. Tyrosinases play a major role in melanin synthesis, and many attempts have been made to identify new natural tyrosinase inhibitors, but few have sought to do in microbes. Postbiotics are bioactive compounds produced by the metabolism of probiotics and have been reported to be safe and effective. In this study, we evaluated the tyrosinase inhibitory effects of culture supernatants of probiotics and discovered novel bacterial metabolites that can be used as a potent tyrosinase inhibitor based on metabolomics. Cultures of Bifidobacterium bifidum IDCC 4201 and Lactiplantibacillus plantarum IDCC 3501 showed effective anti-tyrosinase, reduced melanin synthesis, and altered protein expression associated with the melanogenesis pathway. Comparative metabolomics analyses conducted by GC-MS identified metabolites commonly produced by B. bifidum and L. plantarum. Of eight selected metabolites, phenyllactic acid exhibited significant tyrosinase-inhibitory activity. Our findings suggest that applications of probiotic culture supernatants containing high amounts of phenyllactic acid have potential use as anti-melanogenesis agents in food and medicines.
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SCOPE: Chronic hypernutrition promotes lipid accumulation in the body and excessive lipid accumulation leads to obesity. An increase in the number and size of adipocytes, a characteristic of obesity is closely associated with adipose dysfunction. Recent in vitro and in vivo studies have shown that probiotics may prevent this dysfunction by regulating lipid metabolism. However, the mechanisms of action of probiotics in obesity are not fully understood and their usage for treating obesity remains limited. METHODS AND RESULTS: Bifidobacterium lactis IDCC 4301 is selected for its anti-obesity potential after evaluating inhibitory activity of pancreatic lipase and cholesterol reducing activity. Next, this study investigates the roles of B. lactis IDCC 4301 on lipid metabolism in 3T3-L1 preadipocytes and high-fat diet (HFD)-fed mice. B. lactis IDCC 4301 inhibits cell differentiation and lipid accumulation by suppressing the expression of adipogenic enzymes in 3T3-L1 cells. Moreover, the administration of B. lactis IDCC 4301 decreases body and adipose tissue weight, improves serum lipid levels, and downregulates adipogenic mRNA expression in HFD-fed mice. Additionally, metabolomic analysis suggests that 2-ketobutyrate should be a possible target compound against obesity. CONCLUSIONS: B. lactis IDCC 4301 may be used as an alternative treatment for obesity.
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Fármacos Antiobesidade , Bifidobacterium animalis , Camundongos , Animais , Metabolismo dos Lipídeos , Dieta Hiperlipídica , Fármacos Antiobesidade/farmacologia , Obesidade/metabolismo , Adipogenia , Modelos Animais de Doenças , Colesterol , Células 3T3-L1 , Camundongos Endogâmicos C57BLRESUMO
BACKGROUND: Probiotics have been reported to exhibit positive effects on host health, including improved intestinal barrier function, preventing pathogenic infection, and promoting nutrient digestion efficiency. These internal changes are reflected to the fecal microbiota composition and, bacterial metabolites production. In accordance, the application of probiotics has been broadened to industrial animals, including swine, which makes people to pursue better knowledge of the correlation between changes in the fecal microbiota and metabolites. Therefore, this study evaluated the effect of multi-strain probiotics (MSP) supplementation to piglets utilizing multiomics analytical approaches including metagenomics, culturomics, and metabolomics. RESULTS: Six-week-old piglets were supplemented with MSP composed of Lactobacillus isolated from the feces of healthy piglets. To examine the effect of MSP supplement, piglets of the same age were selected and divided into two groups; one with MSP supplement (MSP group) and the other one without MSP supplement (Control group). MSP feeding altered the composition of the fecal microbiota, as demonstrated by metagenomics analysis. The abundance of commensal Lactobacillus was increased by 2.39%, while Clostridium was decreased, which revealed the similar pattern to the culturomic approach. Next, we investigated the microbial metabolite profiles, specifically SCFAs using HPLC-MS/MS and others using GC-MS, respectively. MSP supplement elevated the abundance of amino acids, including valine, isoleucine and proline as well as the concentration of acetic acid. According to the correlation analyses, these alterations were found out to be crucial in energy synthesizing metabolism, such as branched-chain amino acid (BCAA) metabolism and coenzyme A biosynthesis. Furthermore, we isolated commensal Lactobacillus strains enriched by MSP supplement, and analyzed the metabolites and evaluated the functional improvement, related to tight junction from intestinal porcine enterocyte cell line (IPEC-J2). CONCLUSIONS: In conclusion, MSP administration to piglets altered their fecal microbiota, by enriching commensal Lactobacillus strains. This change contributed amino acid, acetic acid, and BCAA concentrations to be increased, and energy metabolism pathway was also increased at in vivo and in vitro. These changes produced by MSP supplement suggests the correlation between the various physiological energy metabolism functions induced by health-promoting Lactobacillus and the growth performance of piglets.
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Many urinary tract infections (UTIs) are recurrent because uropathogens persist within the bladder epithelial cells (BECs) for extended periods between bouts of infection. Because persistent uropathogens are intracellular, they are often refractive to antibiotic treatment. The recent discovery of endogenous Lactobacillus spp. in the bladders of healthy humans raised the question of whether these endogenous bacteria directly or indirectly impact intracellular bacterial burden in the bladder. Here, we report that in contrast to healthy women, female patients experiencing recurrent UTIs have a bladder population of Lactobacilli that is markedly reduced. Exposing infected human BECs to L. crispatus in vitro markedly reduced the intracellular uropathogenic Escherichia coli (UPEC) load. The adherence of Lactobacilli to BECs was found to result in increased type I interferon (IFN) production, which in turn enhanced the expression of cathepsin D within lysosomes harboring UPECs. This lysosomal cathepsin D-mediated UPEC killing was diminished in germ-free mice and type I IFN receptor-deficient mice. Secreted metabolites of L. crispatus seemed to be responsible for the increased expression of type I IFN in human BECs. Intravesicular administration of Lactobacilli into UPEC-infected murine bladders markedly reduced their intracellular bacterial load suggesting that components of the endogenous microflora can have therapeutic effects against UTIs.
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Antibiose , Infecções por Escherichia coli , Interferon Tipo I , Lactobacillus crispatus , Bexiga Urinária , Infecções Urinárias , Escherichia coli Uropatogênica , Animais , Terapia Biológica , Catepsina D/metabolismo , Infecções por Escherichia coli/imunologia , Infecções por Escherichia coli/microbiologia , Infecções por Escherichia coli/terapia , Feminino , Humanos , Imunidade Inata , Interferon Tipo I/imunologia , Lactobacillus crispatus/fisiologia , Masculino , Camundongos , Bexiga Urinária/imunologia , Bexiga Urinária/microbiologia , Infecções Urinárias/imunologia , Infecções Urinárias/microbiologia , Infecções Urinárias/terapia , Escherichia coli Uropatogênica/crescimento & desenvolvimentoRESUMO
The purpose of this study was to explore students' psychosocial characteristics presumably nurtured in school physical education (PE) and school sports club activities in Korea. In addition, this study attempted to investigate what actual behaviours for each characteristic are observed and could be evaluated. Previous studies related to secondary students' character development in school sports clubs and school PE classes were investigated at the initial stage, and then a panel of 3 experts and 4 host researchers reviewed and selected 9 characteristics and 30 behaviours. Two replicates of a modified Delphi analysis and the Analytic Hierarchy Process (AHP) with 25 and 50 PE teachers respectively were performed and reached 7 characteristics and 21 behavioural indexes and their hierarchy. The content validity ratio (CVR) for seven characteristics in two replicates of a modified Delphi analysis was 0.93. The highest CVR was 1.00 while the lowest was 0.68. The highest CVR among 21 behaviour indexes was 1.00 while the lowest was 0.52, which implied that all the characteristics and the behaviour indexes are valid. In the stage of AHP for each characteristic's hierarchy, "Earnestness" was ranked highest with a weight of 0.215, while "Leadership" was ranked lowest at 0.044 (consistency index and consistency ratio < 0.1). 'Disengaged observation/late in class,' 'helping peer,' and 'opinion coordination' shared the highest score at 0.091 while 'taking initiatives' was placed lowest with 0.010 in the list of 21 behaviour indexes. The results helped infer that PE teachers consider development of interpersonal characteristics and the level of articulation for behaviour indexes important.
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Educação Física e Treinamento , Esportes , Atitude , Humanos , Instituições Acadêmicas , Estudantes/psicologiaRESUMO
Corn-soybean meal diets are commonly used in the pork industry as a primary source of energy and protein. However, such a diet generally contains non-starch polysaccharides (NSPs) which present a challenge in finding ways to improve their availability and digestibility. Dietary multi-carbohydrases (MCs) have been proposed as an efficient approach to utilize NSPs, and can result in improved growth performance and host intestinal fitness. In this study, we evaluated the effects of MC in lactation diets on gut microbiota composition of lactating sows and their litters. The experimental design contained two dietary treatments, a diet based on corn-soybean meal (CON), and CON supplemented with 0.01% multigrain carbohydrases (MCs). Sow and piglet fecal samples were collected on days 7 and 28 after farrowing. Based on the results from 16S rRNA gene amplicon sequencing, MC led to changes in species diversity and altered the microbial compositions in lactating sows and their piglets. Specifically, the MC treatment induced an increase in the proportions of Lactobacillus in piglets. Clostridium and Spirochaetaceae showed a significantly reduced proportion in MC-treated sows at day 28. Our results support the beneficial effects of dietary carbohydrases and their link with improved production due to better host fitness outcomes and gut microbiota composition.
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Microbioma Gastrointestinal , Lactação , Ração Animal/análise , Animais , Dieta/veterinária , Suplementos Nutricionais , Feminino , Glicosídeo Hidrolases , RNA Ribossômico 16S/genética , Glycine max , SuínosRESUMO
To elucidate the role and mechanism of microbes, we combined culture-dependent and culture-independent approaches to investigate differences in gut bacterial composition between sows and weaned pigs. Under anaerobic conditions, several nonselective and selective media were used for isolation from fecal samples. All isolated bacteria were identified and classified through 16S rRNA sequencing, and the microbiota composition of the fecal samples was analyzed by metagenomics using next generation sequencing (NGS) technology. A total of 278 and 149 colonies were acquired from the sow and weaned pig fecal samples, respectively. Culturomics analysis revealed that diverse bacterial genus and species belonged to Firmicutes, Actinobacteria, Proteobacteria, and Bacteroidetes were isolated from sow and weaned pigs. When comparing culture-dependent and culture-independent analyses, 191 bacterial species and 2 archaeal bacterial species were detected through culture-independent analysis, and a total of 23 bacteria were isolated through a culture-dependent approach, of which 65% were not detected by metagenomics. In conclusion, culturomics and metagenomics should be properly combined to fully understand the intestinal microbiota, and livestock-derived microbial resources should be informed by culturomic approaches to understand and utilize the mechanism of host-microbe interactions.
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Iron is an essential element for Vibrio cholerae to survive, and Feo, the major bacterial system for ferrous iron transport, is important for growth of this pathogen in low-oxygen environments. To gain insight into its biochemical mechanism, we evaluated the effects of widely used ATPase inhibitors on the ATP hydrolysis activity of the N-terminal domain of V. cholerae FeoB. Our results showed that sodium orthovanadate and sodium azide effectively inhibit the catalytic activity of the N-terminal domain of V. cholerae FeoB. Further, sodium orthovanadate was the more effective inhibitor against V. cholerae ferrous iron transport in vivo. These results contribute to a more comprehensive biochemical understanding of Feo function, and shed light on designing effective inhibitors against bacterial FeoB proteins.
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Ferro/metabolismo , Vanadatos/farmacologia , Vibrio cholerae/metabolismo , Trifosfato de Adenosina/metabolismo , Azidas/farmacologia , Transporte Biológico , Catálise , Hidrólise , Simulação de Acoplamento MolecularRESUMO
Despite its beneficial properties, effects of betulinic acid on the nutrient-sensing mTOR pathway via insulin or IGF1 signaling remain unclear. Here, we investigated whether betulinic acid reduces intracellular lipid accumulation via the nutrient-sensing pathway in HepG2 cells. Results showed that betulinic acid reduced intracellular lipid accumulation in a dose-dependent manner and inhibited the expression of de novo lipogenesis-related genes and proteins. RNA sequencing analysis revealed the transcriptional modulation of plasma membrane proteins by betulinic acid, and an in silico binding assay indicated an interaction between betulinic acid and IR or IGF1R. Furthermore, betulinic acid downregulated the post-translational modification of the canonical IRS1/PI3K/AKT-pT308 and IGF1/mTORC2/AKT-pS473 pathways, thereby reducing the activity of the mTOR/S6K/S6 pathway. These findings imply that betulinic acid suppresses hepatic lipid synthesis by inhibiting insulin and IGF1 signaling as upstream effectors of the nutrient-sensing mTOR pathway and could be a potent nutraceutical agent for the treatment of metabolic syndromes.
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Insulina , Lipogênese , Humanos , Insulina/metabolismo , Nutrientes , Triterpenos Pentacíclicos , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo , Ácido BetulínicoRESUMO
Vinegar, composed of various organic acids, amino acids, and volatile compounds, has been newly recognized as a functional food with health benefits. Vinegar is produced through alcoholic fermentation of various raw materials followed by acetic acid fermentation, and detailed processes greatly vary between different vinegar products. This study performed metabolite profiling of various vinegar products using gas chromatography-mass spectrometry to identify metabolites that are specific to vinegar production processes. In particular, seven traditional vinegars that underwent spontaneous and slow alcoholic and acetic acid fermentations were compared to four commercial vinegars that were produced through fast acetic acid fermentation using distilled ethanol. A total of 102 volatile and 78 nonvolatile compounds were detected, and the principal component analysis of metabolites clearly distinguished between the traditional and commercial vinegars. Ten metabolites were identified as specific or significantly different compounds depending on vinegar production processes, most of which had originated from complex microbial metabolism during traditional vinegar fermentation. These process-specific compounds of vinegars may serve as potential biomarkers for fermentation process controls as well as authenticity and quality evaluation.
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Staphylococcus aureus RF122 is a major pathogen that causes bovine mastitis, which is the most prevalent and costly disease in the milk and dairy industry. S. aureus expresses various virulence factors that are especially highly associated with iron metabolism, and the bacterial ferrous iron transport system Feo is important for bacterial growth or virulence in mammalian hosts. In this study, we evaluated a new antimicrobial agent, PHT-427, targeting the S. aureus RF122 Feo system for the prevention of bovine mastitis. Various analyses on in vitro enzymatic assays, growth inhibition, virulence expressions, and toxicity of animal model systems were conducted to characterize the inhibition properties of PHT-427. This small molecule efficiently inhibited enzyme activity of FeoB and bacterial growth. PHT-427 attenuated various virulence factors related to milk quality, including staphyloxanthin production, biofilm formation, and coagulation. Considering the high frequency of antibiotic-resistant S. aureus in bovine mastitis isolates, PHT-427 synergistically enhanced bacterial antibiotic susceptibility and further inhibited global Gram-positive bacterial growth. Unlike its effects on bacteria, the inhibitor did not show any toxicity on animal model systems. These results indicate that the S. aureus Feo system represents a good target for antimicrobial strategies, and this new antimicrobial agent may represent a promising biotechnological application for preventing S. aureus-induced bovine mastitis in the milk and dairy industry.
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Anti-Infecciosos , Mastite Bovina , Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Animais , Antibacterianos/farmacologia , Bovinos , Feminino , Mastite Bovina/tratamento farmacológico , Mastite Bovina/prevenção & controle , Testes de Sensibilidade Microbiana , Leite , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/veterinária , Staphylococcus aureusRESUMO
Dry aging is a traditional method that improves meat quality, and diverse microbial communities are changed during the process. Lactic acid bacteria (LAB) are widely present in fermented foods and has many beneficial effects, such as immune enhancement and maintenance of intestinal homeostasis. In this study, we conducted metagenomic analysis to evaluate the changes in the microbial composition of dry-aged beef. We found that lactic acid bacterial strains were abundant in dry-aged beef including Lactobacillus sakei and Enterococcus faecalis. We investigated their abilities in acid and bile tolerance, adhesion to the host, antibiotic resistance, and antimicrobial activity as potential probiotics, confirming that L. sakei and E. faecalis strains had remarkable capability as probiotics. The isolates from dry-aged beef showed at least 70% survival under acidic conditions in addition to an increase in the survival level under bile conditions. Antibiotic susceptibility and antibacterial activity assays further verified their effectiveness in inhibiting all pathogenic bacteria tested, and most of them had low resistance to antibiotics. Finally, we used the Caenorhabditis elegans model to confirm their life extension and influence on host resistance. In the model system, 12D26 and 20D48 strains had great abilities to extend the nematode lifespan and to improve host resistance, respectively. These results suggest the potential use of newly isolated LAB strains from dry-aged beef as probiotic candidates for production of fermented meat.
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Raw milk acts as a mediator of major foodborne pathogenic bacterial infections. However, the sources of pathogens that contaminate milk are often unclear. This study assessed the prevalence of sanitary quality-indicating bacteria (total aerobic bacteria, psychrotrophic bacteria, coliform, and yeast/molds), including seven foodborne pathogens, in a dairy farm environment and processing plant in Korea. The microbiological analysis showed that a few sites, such as vat bottoms, room floors, drain holes, and niches, showed high microbial loads in most dairy farms. Based on quantitative microbial tests, Bacillus cereus was detected in three farms and Staphylococcus aureus was detected in only one farm. Among them, S. aureus JDFM SA01 isolated from a milk filter showed strong biofilm formation and toxicity to the host Caenorhabditis elegans. Subsequently, RNA-seq was performed to characterize the biofilm formation ability of S. aureus JDFM SA01. In biofilms, the significant upregulation of genes encoding microbial surface components and recognizing adhesive matrix molecules promotes adhesion might explain the increased viability and biomass of biofilms. This study provided insight into the prevalence of pathogenic bacteria and microbial contamination levels across dairy farms.
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Being a microbial host for lignocellulosic biofuel production, Saccharomyces cerevisiae needs to be engineered to express a heterologous xylose pathway; however, it has been challenging to optimize the engineered strain for efficient and rapid fermentation of xylose. Deletion of PHO13 (Δpho13) has been reported to be a crucial genetic perturbation in improving xylose fermentation. A confirmed mechanism of the Δpho13 effect on xylose fermentation is that the Δpho13 transcriptionally activates the genes in the non-oxidative pentose phosphate pathway (PPP). In the current study, we found a couple of engineered strains, of which phenotypes were not affected by Δpho13 (Δpho13-negative), among many others we examined. Genome resequencing of the Δpho13-negative strains revealed that a loss-of-function mutation in GCR2 was responsible for the phenotype. Gcr2 is a global transcriptional factor involved in glucose metabolism. The results of RNA-seq confirmed that the deletion of GCR2 (Δgcr2) led to the upregulation of PPP genes as well as downregulation of glycolytic genes, and changes were more significant under xylose conditions than those under glucose conditions. Although there was no synergistic effect between Δpho13 and Δgcr2 in improving xylose fermentation, these results suggested that GCR2 is a novel knockout target in improving lignocellulosic ethanol production.
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The emergence of multidrug-resistant Staphylococcus aureus strains has become a serious clinical problem. Iron is absolutely required for the bacterial growth, virulence associated with colonization, and survival from the host immune system. The FeoB protein is a major iron permease in bacterial ferrous iron transport systems (Feo) that has been shown to play a crucial role in virulence of some pathogenic bacteria. However, FeoB is still uncharacterized in Gram-positive pathogens, and its effects on S. aureus pathogenesis are unknown. In this study, we identified a novel inhibitor, GW3965·HCl, that targets FeoB in S. aureus. The molecule effectively inhibited FeoB in vitro enzyme activity, bacterial growth, and virulence factor expression. Genome-editing and metabolomic analyses revealed that GW3965·HCl inhibited FeoB function and affected the associated mechanisms with reduced iron availability in S. aureus. Gentamicin resistance and Caenorhabditis elegans infection assays further demonstrated the power of GW3965·HCl as a safe and efficient antibacterial agent. In addition to S. aureus, GW3965·HCl also presented its effectiveness on inhibition of the FeoB activity and growth of Gram-positive bacteria. This novel inhibitor will provide new insight for developing a next-generation antibacterial therapy.
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Antibacterianos/farmacologia , Proteínas de Bactérias/efeitos dos fármacos , Benzoatos/farmacologia , Benzilaminas/farmacologia , Compostos Ferrosos/metabolismo , Bactérias Gram-Positivas/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Animais , Antibacterianos/química , Proteínas de Bactérias/química , Transporte Biológico , Caenorhabditis elegans/efeitos dos fármacos , Farmacorresistência Bacteriana/efeitos dos fármacos , Gentamicinas/farmacologia , Bactérias Gram-Positivas/crescimento & desenvolvimentoRESUMO
Increasing evidence indicates that alterations in gut microbiota are associated with mammalian development and physiology. The gut microbiota has been proposed as an essential player in metabolic diseases including brain health. This study aimed to determine the impact of probiotics on degenerative changes in the gut microbiota and cognitive behavior. Assessment of various behavioral and physiological functions was performed using Y-maze tests, wheel running tests, accelerated rotarod tests, balance beam tests, and forced swimming tests (FSTs), using adult mice after 50 weeks of administering living probiotic bacterium Lactobacillus fermentum strain JDFM216 or a vehicle. Immunomodulatory function was investigated using immune organs, immune cells and immune molecules in the mice, and gut microbiota was also evaluated in their feces. Notably, the L. fermentum JDFM216-treated group showed significantly better performance in the behavior tests (P < 0.05) as well as improved phagocytic activity of macrophages, enhanced sIgA production, and stimulated immune cells (P < 0.05). In aged mice, we observed decreases in species belonging to the Porphyromonadaceae family and the Lactobacillus genus when compared to young mice. While administering the supplementation of L. fermentum JDFM216 to aged mice did not shift the whole gut microbiota, the abundance of Lactobacillus species was significantly increased (P < 0.05). Our findings suggested that L. fermentum JDFM216 also provided beneficial effects on the regulation of immune responses, which has promising implications for functional foods. Taken together, L. fermentum JDFM216 could confer the benefit of improving health with enhanced cognition, physiological behavior, and immunity by modulating the gut microbiota.