The present disclosure provides AprL-clade protease enzymes, including variant AprL-clade protease enzymes, nucleic acids encoding same, and compositions and methods related to the production and use thereof, including an AprL-clade variant subtilisin enzyme that has improved stability and/or soil removal compared to a parent AprL-clade subtilisin enzyme. Địa chỉ: Số 22, Lô 7,8 - Khu đô thị Văn Khê - Phường La Khê - Quận Hà Đông - TP Hà Nội. Thành phần Mỗi ống có chứa 3 tỷ bào tử lợi khuẩn Bacillus clausii và Bacillus subtilis Nước muối sinh lý (0,9%). Công dụng Vệ sinh tai, mũi, họng hàng ngày Giảm triệu chứng sổ mũi Bacillus clausii PBC429 benefits. Promotes a healthy gut microbiome. Possesses immunomodulatory activities. Inhibit the growth of pathogens in the intestinal tract. Can withstand harsh environments like acidic pH, high temperature. Bacillus clausii is useful in the treatment of diarrhoea and the prevention of antibiotic-associated diarrhoea. Probiotics. Bacillus species are sometimes used as probiotics in both animals and humans. Bacillus subtilis, Bacillus clausii, B. cereus, B. coagulans, and B. licheniformis have been the most extensively examined. It is clear that few scientific studies have been performed on the potential of these species as probiotics, especially compared Bào tử lợi khuẩn tốt cho mẹ và bé PregMom. LiveSpo PregMom chứa 3 tỷ lợi khuẩn sống bao gồm Bacillus Subtilis, Bacillus Clausii, Bacillus Coagulans và 5ml nước cất giúp giảm táo bón, tiêu chảy và khó tiêu thông thường. Sản phẩm đặc biệt thích hợp cho trẻ nhỏ và phụ nữ mang thai. Microbiome Labs RestorFlora Probiotic Supplement - Saccharomyces boulardii, Bacillus subtilis HU58 & Bacillus clausii Spore & Yeast Probiotics - Gut, Immune & Digestive Health Support (50 Capsules) 50 Count (Pack of 1) tKEOu. Bacillus subtilis là một loại vi khuẩn có trong hệ tiêu hóa của con người và chúng mang lại những lợi ích nhất định cho chúng ta. Để hiểu rõ về loại vi khuẩn có lợi này, bạn hãy theo dõi bài viết ngay sau đây để được chuyên gia phân tích về chủ đề Bacillus subtilis là gì và có tác dụng gì với hệ tiêu hóa của trẻ? subtilis là gì?Bacillus subtilis là một lợi khuẩn đường ruộtBacillus subtilis là vi khuẩn gram dương hay còn được gọi là trực khuẩn cỏ, hay trực khuẩn rơm, vì đây là một loại vi khuẩn có trong cỏ, rơm, và cả đất nữa. Tuy nhiên chúng phát triển nhiều trong hệ tiêu hóa và mang lại nhiều tác dụng có lợi cho con người nên Bacillus subtilis được gọi là lợi khuẩn đường subtilis là trực khuẩn hình que, chúng thường tạo thành dạng bào tử để tăng khả năng sinh sống và phát triển trong môi trường khắc một tế bào Bacillus subtilis thì nó có khả năng phân đôi thành hai tế bào con đối xứng , hoặc phân chia không đối xứng để tạo các dạng bào tử trong môi trường khắc nghiệt như Chất dinh dưỡng nghèo nàn, bức xạ cao, hay hạn hán...Đặc biệt trong môi trường sống khắc nghiệt thì chúng có thể tự tạo kháng sinh để giết chết đồng loại cạnh tranh dinh dưỡng trước khi chúng hình thành bào subtilis là gì? Bacillus clausii có tác dụng gì với hệ tiêu hóa của trẻ?Chính vì tính ổn định cao của bào tử trong điều kiện sống khắc nghiệt nên trong các dạng chế phẩm thì Bacillus subtilis thường ở dạng bào tử. Khi uống vào cơ thể con người thì các dạng bào tử không bị tiêu diệt bởi acid dịch vị, sau đó vào trong ruột, các bào tử này sẽ phát triển thành dạng hoạt động giúp cơ thể cân bằng vệ vi khuẩn có lợi, và cải thiện chức năng tiêu hóa trong trường hợp sử dụng kháng sinh kéo Bào tử Bacillus subtilis có tác dụng gì đối với hệ tiêu hóa của trẻ?Bào tử Bacillus subtilis có rất nhiều tác dụng đối với trẻKhi uống các chế phẩm có chứa bào tử Bacillus subtilis thì các dạng bào tử này sẽ bền vững đi qua dạ dày, tới ruột non. Đến đây chúng nảy mầm thành các dạng lợi khuẩn giúp tạo hệ vi khuẩn có lợi cho hệ tiêu hóa của trẻ. Đồng thời cung cấp các chất dinh dưỡng và kích thích hệ miễn dịch cho trẻ. Bacillus subtilis là một loại vi khuẩn chí đường ruột, rất an toàn và không hề tạo bất cứ một loại chất nào có hại cho sức khỏe của con subtilis có khả năng tạo ra các enzym tiêu hóa như Amylase, protease, cellulose,...giúp củng cố chức năng hệ tiêu hóa và tăng khả năng hấp thu chất dinh dưỡng ở ra việc bổ sung lợi khuẩn Bacillus subtilis còn giúp tăng cường hệ vi khuẩn có lợi cho đường ruột, cung cấp thêm các chất dinh dưỡng và tăng sức đề kháng cho cơ thể của subtilis tăng cường sức đề kháng của trẻBacillus subtilis còn có tác dụng đồng hóa một số loại vitamin như vitamin B2 Đây là loại vitamin có mặt hầu hết trong các tế bào và tham gia vào quá trình dinh dưỡng và hô hấp của cơ thể con cạnh đó Bacillus subtilis còn có thể sản xuất ra một số loại kháng sinh để ức chế sự sinh trưởng và tiêu diệt những vi sinh vật có hại, giúp trẻ tăng cường miễn dịch, tăng khả năng phòng ngừa một số loại bệnh tật. Đồng thời nó có khả năng kích thích cơ thể tăng sản sinh các kháng thể IgA trên bề mặt hệ tiêu hóa giúp ức chế sự xâm nhập của các vi khuẩn gây bệnh cho Amano Enzyme bổ sung lợi khuẩn bacillus subtilis cho trẻ có một hệ tiêu hóa Enzyme tăng cường chức năng tiêu hóa, giúp trẻ ăn ngonAmano Enzyme là enzym tiêu hóa có chứa các nhóm thành phần như Lợi khuẩn, vitamin và khoáng chất, Enzyme, Lysine, Kẽm gluconat,..Hai chủng lợi khuẩn ở dạng bào tử là Bacillus subtilis và Bacillus clausii. Hai chủng này giúp tăng cường chức năng hệ tiêu hóa, hỗ trợ trẻ ăn ngon miệng và tăng sức đề tiêu hóa Amano Enzyme còn chứa rất nhiều các enzym tiêu hóa như amylase, protease Đây là các enzym giúp tăng cường phân giải thức ăn thành các chất dễ hấp thu hơn. Do đó giúp trẻ tăng khả năng hấp thu các chất dinh dưỡng và tăng cân đều có trong sản phẩm còn giúp tăng cường hệ miễn dịch và kích thích tăng bài tiết của các enzym tiêu hóa hơn từ đó góp phần giúp trẻ ăn ngon gluconat Giúp tăng cường sự nhạy cảm của vị giác, giúp trẻ có cảm giác ngon miệng hơn. Đồng thời tăng miễn dịch, chống nhiễm vitamin và khoáng chất Các vitamin nhóm B B1, B5, B6,.. , vitamin D3, canxi, magie, DHA...nhằm cung cấp các chất dinh dưỡng cần thiết cho cơ thể trẻ giúp trẻ phát triển một cách toàn diện về thể chất và trí Enzyme thích hợp cho các đối tượng nhưTrẻ biếng ăn, ăn cảm giác không ngon miệng, chậm tăng cân, hay người đang trong giai đoạn phục hồi sức khỏe sau có chức năng tiêu hóa kém do thiếu enzym tiêu hóa, hoặc người bị mất cân bằng hệ vi sinh đường ruột do sử dụng kháng sinh kéo Xem thêm Bacillus clausii là gì, có tác dụng gì với hệ tiêu hóa trẻ->> Xem thêm Hướng dẫn cách dùng amanoenzym ->> Xem thêm Trẻ bị đi ngoài mẹ cần chuẩn bị những món gì For example, the Bacillus clausii metE gene, which encodes a B12-independent form of methionine synthase, is regulated by tandem S box and B12 Comprehensive Natural Products II, 2010BACILLUS IntroductionI. Jenson, in Encyclopedia of Food Microbiology Second Edition, 2014ProbioticsBacillus species are sometimes used as probiotics in both animals and humans. Bacillus subtilis, Bacillus clausii, B. cereus, B. coagulans, and B. licheniformis have been the most extensively examined. It is clear that few scientific studies have been performed on the potential of these species as probiotics, especially compared with the application of lactic acid bacteria. Bacillus have the obvious advantage over other potential probiotics that they can be produced efficiently and cost effectively by drying and survive well through shelf life. They also will survive gastric acidity and survive into the bowel, the reputed site of action. At least some strains are able to germinate and reproduce in the human gastrointestinal tract. A number of products are registered for human use and also for animal use pigs, poultry, calves, aquaculture. Most products on the market do not have extensive clinical trial data. Claims often relate to extragastrointestinal effects, such as alleviation of allergy symptoms and rheumatoid arthritis symptoms, but claims for gastrointestinal efficacy are made for some products. The mechanisms by which bacilli may be effective as probiotics is not known. Some strains have been shown to produce extracellular is a B. subtilis–fermented soybean product, native to Japan, for which health benefits often have been ascribed. It is popular as a breakfast food. Natto has a strong odor and flavor and a viscous, stringy texture. In part, this is due to the production of a cell capsule of poly-γ-glutamic acid in stationary phase. Some B. cereus probiotic products are produced from strains that produce enterotoxin or at least contain enterotoxin full chapterURL of BIOVIA Materials Studio, LAMMPS, and GROMACS in Various Fields of Science and EngineeringSumit Sharma, ... Rakesh Chandra, in Molecular Dynamics Simulation of Nanocomposites Using BIOVIA Materials Studio, Lammps and Gromacs, Applications of GROMACSThe following paragraphs will explain the utility of GROMACS in various areas. Padmanabhan et al. [18] explored an eco-friendly method for the production of silver nanoparticles from Bacillus clausii cultured from Enterogermina. Along with the biosynthesis and conformity test, in silico studies were done on nicotinamide adenine dinucleotide phosphate NADPH-dependent nitrate reductase enzymes from the viewpoint of designing a rational enzymatic strategy for the synthesis. The detailed characterization of the nanoparticles was carried out using UV-vis spectroscopy, dynamic light scattering DLS particle size analysis, transmission electron microscopy TEM, and x-ray diffraction XRD analysis. Computational profiling and in silico characterization of NADH-dependent enzymes were carried out based on literature. Nitrate reductase sequence was retrieved from National Center for Biotechnology Information NCBI for characterization. Secondary structure was evaluated and verified by JPred and Self-Optimized Prediction Method with Alignment SOPMA tool. Tertiary structure was also modeled by MODELLER and Iterative Threading ASSEmbly Refinement I-TASSER parallel, and the best structure was selected based on energy values. Structure validation was done by GROMACS, and root-mean-square deviation RMSD, root-mean-square fluctuation RMSF, and temperature variation plot were also plotted. Interaction graphs between nitrate reductase and ligand silver nitrate were done through molecular docking using et al. [19] provided a data package of GROMACS input files for atomistic MD simulations of multicomponent, asymmetrical lipid bilayers using the optimized potentials for liquid simulations-all atom OPLS-AA force field. The data included 14 model bilayers composed of eight different lipid molecules. The lipids present in these models were cholesterol CHOL, 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylcholine POPC, 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylethanolamine POPE, 1-stearoyl-2-oleoyl-sn-glycero-3-phosphatidylethanolamine SOPE, 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylserine POPS, 1-stearoyl-2-oleoyl-sn-glycero-3-phosphatidylserine SOPS, N-palmitoyl-d-erythro-sphingosyl-phosphatidylcholine SM16, and N-lignoceroy l-d-erythro-sphingosyl-phosphatidylcholine SM24. The bilayers' compositions were based on lipidomic studies of PC-3 prostate cancer cells and exosomes discussed in Llorente et al. [20], showing an increase in the section of long-tail lipid species SOPS, SOPE, and SM24 in the exosomes. Former knowledge about lipid asymmetry in cell membranes was accounted for in the models, meaning that the model of the inner leaflet was composed of a mixture of PC, PS, PE, and cholesterol, while the extracellular leaflet was composed of SM, PC, and cholesterol discussed in Van Meer et al. [21]. The provided data include lipids' topologies, equilibrated structures of asymmetrical bilayers, all force field parameters, and input files with parameters describing simulation conditions The data were associated with the research article by Róg et al. [22].Róg et al. [23] provided topologies and force field parameter files for MD simulations of lipids in the OPLS-AA force field using the GROMACS package. This was the first systematic parameterization of lipid molecules in this force field. Topologies were provided for four phosphatidylcholines saturated dipalmitoylphosphatidylcholine DPPC, mono-cis-unsaturated POPC and 1,2-dioleoyl-sn-glycero-3-phosphocholine DOPC, and mono-trans-unsaturated phosphoenolpyruvate carboxylase PEPC. Parameterization of the phosphatidylcholines was achieved in two steps first the authors supplemented the OPLS force field parameters for DPPC with new parameters for torsion angles and van der Waals parameters for the carbon and hydrogen atoms in the acyl chains and new partial atomic charges and parameters for torsion angles in the phosphatidylcholine and glycerol moieties [24]. Next, parameters were derived for the cis- and transdouble bonds and the neighboring single bonds [25]. Additionally the authors provided GROMACS input files with parameters describing simulation conditions which were strongly recommended to be used with these lipid models. The data were associated with the research article by Kulig et al. [25] and provided as supporting the study by Lemkul [26], users are provided the rationale and a theoretical explanation for the command-line syntax in each step in the online tutorials available at and the underlying settings and algorithms necessary to perform robust MD simulations in each full chapterURL in Biomedical ResearchK. Mikawlrawng, in New and Future Developments in Microbial Biotechnology and Bioengineering, 2016ProbioticsIt is a well established fact that some intestinal microfloras perform several important functions including metabolic, trophic, and protective ones for the body. Probiotics are formulations of live microbial cells such as Bacillus clausii, Lactobacillus, and Bifidobacterium that contribute to intestinal microbial balance. Probiotics play a vital role in directly maintaining gastrointestinal microbial balance in particular, and increasing the immunity of the entire body in general. Their benefits to human and animal health have been proven in countless scientific researches. Probiotics literally means “for life,” and they are microorganisms that are associated with benefical effects for humans and animals. Regular consumption of food containing probiotic microorganisms is recommended for establishment of a positive balanced population of useful or beneficial intestinal flora. They play an important role in the protection of the organism against harmful microbes and also strengthen the immune system of the host. Probiotics are also usually consumed after antibiotic therapy, the result of which may have destroyed beneficial microbial flora of the digestive tract. However, those probiotic formulations containing some Bacillus species are recommended for use along with antibiotics since these strains eg, B clausii are resistant to antibiotics Coppi et al., 1985. Generally, the probiotic formulations consist mostly of the strains of the genera Bacillus, Lactobacillus, and Bifidobacterium, but reports are now available about the use of other strains of bacteria such as Enterococcus and Streptococcus, and even fungi such as Aspergillus and Saccharomyces Fox, 1988. With the advancement in understanding of the ecology of gastrointestinal microbes and their roles it can be speculated that more desirable microbes from fungi will join the list of full chapterURL to Polyphenolic Compounds Modulates Type 1 Diabetes The Case of GenisteinGuannan Huang, ... Tai L. Guo, in Polyphenols Mechanisms of Action in Human Health and Disease Second Edition, ProbioticsProbiotics are defined as “mono- or mixed cultures of live microorganisms that can beneficially affect the host by improving the properties of the indigenous microflora” [99]. Common probiotic components include Bifidobacterium breve, Bifidobacterium longum, Bifidobacterium infantis, Bacillus clausii, Lactobacillus acidophilus, Lactobacillus GG, Lactobacillus plantarum, Lactobacillus paracasei, Lactobacillus bulgaricus, and Streptococcus thermophiles [100]. In a prospective cohort study, probiotic supplementation at the age of 0–27 days in infants was associated with a decreased risk of islet autoimmunity comparing with probiotic supplementation after 27 days [101]. One study performed in NOD mice found that the oral probiotic VSL3 can effectively prevent T1D while inducing antiinflammatory IL-10 production [102]. Similarly, in another study, oral administration of VSL3 in NOD mice prevented T1D by inhibiting IL-1β expression and releasing components of inflammasome [103]. Moreover, by orally transferring Lactobacillus johnsonii strain from Biobreeding diabetes-resistant rats to BB-DP rats, a study found that the probiotics conferred T1D protection in diabetes-prone rats through enhanced Th17 differentiation [104]. In addition, it was reported that the combinatorial use of probiotics and vitamin C could effectively reduce BGL more than vitamin C alone in an alloxan-induced Wistar rat model [105].Read full chapterURL Ward, ... A. Kulkarni, in Encyclopedia of Microbiology Third Edition, 2009Bacillus Protease ProductionEnzymes produced by Bacillus species represent about 50% of the total enzyme market with the Bacillus alkaline serine proteases subtilisins being the single most dominant commercial enzyme because of its application in household detergents. The most important commercial serine alkaline protease, subtilisin Carlsberg, produced by B. licheniformis, consists of a single peptide chain with 274 amino acid residues, contains no cysteine amino acids, and consequently has no disulfide bonds. This enzyme is also produced by Bacillus pumilus. Another Bacillus serine alkaline protease, subtilisin BPN, produced by B. amyloliquefaciens, B. subtilis, and B. stearothermophilus has little commercial significance compared with subtilisin Carlsberg. While the enzyme structures have significant similarities, the Carlsberg enzyme has a broader pH-activity curve, and it retains a much greater percentage of its optimum pH activity, when the pH is reduced to three largest enzyme manufacturers, Novo Nordisk, Genencor International, and DSM have reported market shares of about 41–44, 21, and 8%, respectively, with other producers in North America, Europe, and Asia accounting for most of the remaining 27–30%. Commercial proteases from some of the major manufacturers are listed in Table 2. The subtilisin Carlsberg-type alkaline serine protease is produced by B. licheniformis, B. pumilus, and B. subtilis. Highly alkalophilic Bacillus species, such as Bacillus clausii and Bacillus halodurans, produce more highly alkaline stable enzymes used in heavy-duty detergent formulations, such as Esperase produced by Novo Nordisk. Commercial neutral proteases produced by Bacillus species have activity optima in the region of pH 7 and these are zinc metalloproteases. They have applications in milk and soy protein modification, in brewing for control of amino nitrogen, and in optimization of cereal mash extraction and chill-haze removal. Commercially important proteases of Bacillus species are typically produced constitutively, and the production is associated with the exponential and postexponential phases of 2. Examples of commercial proteases’ sources, applications, and their industrial suppliersSupplierProduct trade nameMicrobial sourceApplicationNovo Nordisk, DenmarkAlcalaseBacillus licheniformisDetergent high alkaline, high temperature, silk degumming, protein hydrolysates, meat processing, fuel alcohol fermentation enhancementBiofeed proB. licheniformisFeedDurazymBacillus lentusDetergent, food, silk degummingEverlaseBacillus spDetergent bleach stableFlavorzymeAspergillus oryzaeProtein hydrolysates mixture of exo-, endo-proteasesKannaseBacillus cold washKojizymeNot specifiedProtein hydrolysatesNeutraseB. subtilisBrewing and bakingNovoBate WBBacillus 243B. licheniformisDenture cleanersNovozyme 539HP FGenetically modified Bacillus broad specificity, hydrolyses amide, and ester bonds, enantioselective catalyst in synthesis of optically active amines, alcohols, carboxylic acids, and amines; peptide synthesisNUEBacillus liming active at pH 12–13OvozymeBacillus detergent egg inhibitor-resistantProtamexBacillus protease complexProduction of protein hydrolysates, flavor development, and meat higher pH, medium temperature, AGenetically modified Bacillus broad specificity, hydrolyses amide and ester bonds, enantioselective catalyst in synthesis of optically active amines, alcohols, carboxylic acids, and amines; peptide synthesisGenencor International, USAAcid fungal proteaseAspergillus hydrolysisFermgenBacillus fermentationsFungal proteaseAspergillus dairy-selective protein hydrolysisHT proteolyticBacillus hydrolysis high temperatureMultifect neutralBacillus hydrolysis neutral pH, wheat ethanol fermentationPrimatanBacterial sourceLeather batingProperaseBacillus high alkaline, low temperatureProtexBacillus hydrolysis alkalinePurafectB. lentusDetergent high alkaline, leather alkaline soakDSM, NLAccelerezymeNon GMOCheesemaking – flavor developmentBakeZyme B500BGBacillus B500BGAspergillus proteaseBacillus neutral proteaseFromaseRhizomucor coagulantMaxirenRecombinant Kluyveromyces lactisCheesemaking fermentation produced chymosinSuparen/SurecurdCryphonectria parasiticaCheesemaking fungal coagulantAmanoPharmaceuticals JPAcid protease AA. nigerProtein hydrolysis pH protease DSA. nigerDietary supplementCollagenaseClostridium cultureNewlase FRhizopus niveusProtein hydrolysis pH hydrolysis pH 10Protease A 2A. oryzaeProtein hydrolysis pH A-DSA. oryzaeDietary supplementProtease DSA. melliusDietary supplementProtease MA. oryzaeProtein hydrolysis pH NB. subtilisBiotransformations, protein hydrolysisProtease SB. stearothermophilusBiotransformations, protein hydrolysisProtinBacillus bating, dehairing, and silver recovery pH 10–11ProzymeAspergillus melliusDigestive aidStreptokinase/streptodornaseStreptococcus pharmaceuticalThermoaseBacillus bating, dehairing, and silver recovery pH 7– Development, USAEnzeco alkaline proteaseB. licheniformisIndustrial pH alkaline protease-L FGB. licheniformisFoodEnzeco high alkaline proteaseBacillus neutral bacterial proteaseB. subtilisFood, meat tenderizingEnzeco neutral bacterial proteaseB. licheniformisVegetable protein hydrolysis pH 6– species are attractive hosts for production of proteases for a variety of reasons. They exhibit high growth rates, which result in short fermentation cycles. Several strains of Bacillus, including B. subtilis and B. licheniformis, have GRAS status from the United States Food and Drug Administration, which means these organisms and their products are generally regarded as safe. The complete sequence of B. subtilis and a number of other Bacillus species have now been published, which is facilitating the further development and engineering of these strains and their enzyme products. Bacillus species, including B. subtilis, B. licheniformis, and B. amyloliquefaciens, have a high capacity to secrete the proteases of interest into the extracellular medium. In this regard, the identification of several genes in the B. subtilis genome, which encode proteins of the major secretion pathway, including five type-I signal peptidase genes and one type-II signal peptidase, was of special significance. Genomic analysis of the alkaliphilic B. halodurans has also been especially interesting from the perspective of producing commercial alkaline proteases. Through protein engineering techniques, it has been possible to develop commercial protease variants of the B. clausii alkaline protease to generate enzymes with improved performance for use in low-temperature washes and in bleach containing variety of molecular strategies are used for development of recombinant Bacillus strains for commercial production. Engineered versions of natural plasmids from the same organism or a closely related species are introduced into hosts using transformation, cell fusion, and electroporation approaches. Native promoters, such as the promoter of the highly efficient B. subtilis α-amylase, are often exploited. It was found that more stable clones could be developed by direct insertion of DNA into the chromosome. Antibiotic resistance strategies cannot be used in commercial enzyme production fermentations for stable plasmid maintenance, and other strategies such as incorporating the only copy of another gene required for microbial growth into the plasmid have been used. Amplification of gene copy number has generated high enzyme-producing strains. It has been suggested that the ideal production strain is a genetically stable and chromosomally integrated gene, supported by high levels of expression and a different context, the ability of Bacillus species to produce both a large variety and high quantities of extracellular proteases has presented a barrier to the use of these hosts for production of cloned foreign proteins because the proteases tend to degrade the secreted cloned proteins. As a result, strategies to use protease-deficient mutants have been employed and successfully used to produce a number of intact heterologous full chapterURL Pacifici, ... Claes Ohlsson, in Marcus and Feldman's Osteoporosis Fifth Edition, Effects of probiotics on bone mass in rodentsProbiotic is defined as “live microorganisms that, when administered in adequate amounts, confer a health benefit on the host” [58] One important advantage of using probiotic treatment compared with the GF mouse model when evaluating the role of the GM for adult bone metabolism is that no developmental effects might confound the findings. Probiotic treatments changes composition and/or metabolic activity in an already present GM. A large number of studies have evaluated the role of probiotic treatments in different rodent bone disease models as well as in healthy gonadal intact rodents and these studies, which in general have reported beneficial effects of probiotic treatment on skeletal health, will be summarized in this section [43,57,59–74]. Ovariectomized rodent modelsThe rapid bone loss caused by the pronounced drop in estradiol levels during menopause contributes to the lower bone mass and higher risk of fractures in women compared with men [75,76]. Current available approved osteoporosis medications have postmenopausal osteoporosis as a main indication. The rodent ovariectomy ovx-model is a well-established animal model of postmenopausal et al. was the first to show in a preventive study that probiotics can protect from ovx-induced bone loss in mice [64]. The ovx-mice were treated with either a single Lactobacillus paracasei or a mix of L. paracasei and Lactobacillus plantarum. Both treatments protected the mice from ovx-induced bone loss, and this was associated with decreased expression of inflammatory cytokines and increased frequency of regulatory T cells in the bone marrow. Shortly after this study, an independent study by Britton et al. confirmed that probiotics has the capacity to protect mice from ovx-induced bone loss [60]. These authors demonstrated that preventive treatment with Lactobacillus reuteri protected mice from ovx-induced bone loss associated with decreased osteoclastic gene expression in the bone marrow. Sex steroid deficiency increases intestinal permeability causing inflammation that can lead to bone loss [43,77]. In an elegant study by Li et al. it was demonstrated that treatment with Lactobacillus rhamnosus GG or the combination of probiotic strains known as VSL3 protected from ovx-induced bone loss associated with a protection from increased intestinal permeability, suggesting that probiotics at least partly may protect from ovx-induced bone loss via a modulation of the intestinal permeability and thereby inflammation [43] Fig. Moreover, Lactobacillus acidophilus treatment protected mice from ovx-induced bone loss by decreasing inflammatory cytokines and increase regulatory T cells in both bone marrow and spleen [72]. Besides treatment with several different Lactobacillus strains, both Bacillus clausii and Bifidobacterium longum, have been reported to protect rodents from ovx-induced bone loss [63,64,67,68,71,73,74]. Collectively, these studies clearly demonstrate that probiotic treatments have the capacity to protect female rodents from ovx-induced bone loss. Currently, it has not been reported if probiotics may also protect male rodents from castration-induced bone Healthy gonadal intact rodentsThe effect of probiotics on the skeleton has also been investigated in healthy gonadal intact female and male rodents. McCabe et al. was the first to show that probiotic treatment, using L. reuteri, increased the trabecular bone mass in femur and vertebra in healthy gonadal intact male but not female mice [59]. The increased bone mass in male mice was associated with decreased intestinal inflammation. Collins et al. demonstrated that the positive effects of L. reuteri on bone mass in healthy gonadal intact male mice is dependent on lymphocytes [78]. Two other studies support that treatment with certain Lactobacillus strains does not increase bone mass in healthy gonadal intact female mice [60,64]. In contrast, treatment with L. rhamnosus GG was in another study shown to increase trabecular bone mass in both femur and spine in healthy gonadal intact female mice [43]. In a subsequent study it was reported that the increased trabecular bone mass by L. rhamnosus GG treatment was associated with increased intestinal production of the SCFA butyrate. Butyrate diffuses to the bone marrow where it increases the number of regulatory T cells. This lineage stimulates the production of the osteogenic Wnt ligand Wnt10b by CD8+ T cells. Wnt10b activates Wnt signaling in osteoblastic cells, thus stimulating bone formation in healthy gonadal intact female mice [79]. Taken together, the effect of Lactobacillus on bone mass in healthy gonadal intact mice might be strain dependent, and it is also possible that the animal facility or the genetic background of the mouse strain used might contribute to the conflicting results regarding the effects of different probiotic treatments on bone mass in healthy gonadal intact Inflammation-induced bone lossPerturbations in the GM homeostasis can be caused by pathogens, antibiotic treatment, and diet causing inflammation, tissue destruction and dysbiosis that may lead to disease development [80]. Perturbed microbial composition has been postulated to be involved in a range of inflammatory conditions, within and outside the gut, including inflammatory bowel diseases, rheumatoid arthritis RA, multiple sclerosis, food allergies, eczema, and asthma as well as obesity and the metabolic syndrome [23,24]. Low-grade inflammation has been reported to affect physiological bone turnover and play a role in pathological skeletal conditions such as osteoporosis [81–84]. Furthermore, gut-associated inflammatory and autoimmune conditions have been associated with low bone mass [85,86]. Recently, the protective capacity of probiotic treatments for bone health in inflammation-induced bone loss has been evaluated in different rodent disease models. In one study, L. reuteri increased bone mass in female mice that were subjected to dorsal skin incision to induce a chronic inflammation [61]. Treatment with L. reuteri was also shown to prevent type 1 diabetes induced bone loss in male mice by increasing Wnt10b expression [62]. The autoimmune disease RA is associated with severe bone destructions. Treatment with Lactobacillus casei in adjuvant-induced arthritis in rats partly protected against the inflammation-induced bone loss and this protective effect was associated with decreased inflammatory cytokine levels in serum [87]. Taken together, available evidence indicate that at least certain Lactobacillus strains have the capacity to protect rodents from inflammation-induced bone Probiotics modulates the effects of medications on bone health in rodentsOne may hypothesize that different prescribed medications may exert their positive or negative effects on bone health via different GM dependent mechanisms and some recent studies support this notion Fig. Glucocorticoids GCs are immune-modulating drugs with severe side effects, including GC-induced osteoporosis. It was recently shown in a groundbreaking study that GCs treatment in mice alters the GM composition [88]. Importantly, depletion of the GM by broad spectrum antibiotics prevented the GC-induced bone loss, demonstrating that the GM is crucial for mediating GC-induced bone loss. Interestingly, treatment with L. reuteri prevented from GC-induced bone loss by protecting from increased intestinal permeability and increased apoptosis of osteoblasts and osteocytes. Severe bone loss is associated with the antiretroviral agent tenofovir disoproxil fumarate TDF which has been widely used as a first-line treatment of human immunodeficiency virus HIV and hepatitis B virus HBV infections worldwide [89] TDF plays an antiretroviral role by inhibiting adenine analog reverse transcription and improves the survival of patients with HIV or HBV [90]. However, TDF treatment is associated with substantially increased bone resorption and bone loss that is larger compared with other anti-HIV agents [91,92]. Recently, it was shown in a mouse model that L. rhamnosus GG prevented TDF-induced bone loss, and this protection was associated with increased intestinal barrier integrity, expanded regulatory T cells, decreased Th17 cells, and downregulated osteoclastogenesis-related cytokines in the bone marrow, spleen, and gut in the TDF treated mice [89]. In a study by Schepper et al., they evaluated the postantibiotic effects on bone and found that mice that were treated with L. reuteri or a mucus supplement were protected from postantibiotic bone loss by preventing from increased intestinal permeability [57]. These three recent important studies demonstrate that probiotic treatment has the capacity to prevent medication-induced bone loss involving the GM and future clinical studies should determine if GCs and/or TDF regulate the human GM composition and if the deleterious effects of GCs and TDF on bone health might be avoided by specific probiotic as recently described for the first-line medication for treatment of type 2 diabetes metformin, the GM might also contribute to the beneficial bone effects of the different available osteoporosis treatments [93]. Metformin was reported to alter the gut microbiome of individuals with treatment-naïve type 2 diabetes, contributing to the therapeutic effect of the drug. It was first demonstrated in descriptive studies that metformin altered the GM composition in humans and subsequent functional studies, using fecal transplantation from metformin-treated donors to GF mice, revealed that metformin treatment of the donors improved the glucose tolerance in the recipient mice [93]. Intermittent treatments with PTH analogs are approved for osteoporosis treatment, and in a recent report, it was demonstrated that the GM is permissive for the bone anabolic effect of intermittent PTH treatment in mice [94]. In that study, it was shown that intermittent PTH does not increase bone mass in GF mice or mice with the depletion of GM using broad spectrum antibiotics. Subsequent mechanistic studies revealed that the GM produces permissive butyrate acting on GPR43 to enable intermittent PTH to increase Treg cells and thereby bone formation [94]. Thus there is now data from animal studies that at least some of both the negative and positive effects of different medications on bone health are mediated via or dependent on the GM. Future human translational studies are clearly warranted to determine if the effect of different medications on bone health is dependent or mediated via the GM also in full chapterURL on bacterial secretomes enlighten research on Mycoplasma secretomeMuhammad Zubair, ... Aizhen Guo, in Microbial Pathogenesis, Bacillus clausii secretomeDifferential secretome among bacterial strains helps to indicate the virulent properties associated with specific strain such as Bacillus clausii probiotic strains [9]. Many pathogenic bacterial secretome has been probed and found crucial virulence or pathogenesis related factors that can be the source of diagnostic markers or candidate for effective vaccine development. Rather than the numbers of studies that have been conducted in this field, the investigation of secretome at molecular level remains in need. Whereas the identification of various secreted proteins and their pathogenic functions including cell interaction, adhesion, invasion, apoptosis and/or inflammatory response might add a great progress in this field. Such kind of studies may lead to the discovery of novel antigens that might be useful as diagnostic markers, vaccine and drug full articleURL regulation RNA special issueRebecca L Coppins, ... Eduardo A Groisman, in Current Opinion in Microbiology, 2007New riboswitch architecturesThe vast majority of riboswitches sense single metabolites to modulate gene expression. However, Breaker's laboratory [15••] has now provided the first examples of mRNAs harboring two riboswitches in tandem in their 5’-UTR regions, each responding to a different metabolite Figure 1. They demonstrated that the metE mRNA from Bacillus clausii has, in its 5′-region, two distinct riboswitches one responding to S-adenosylmethionine and another responding to coenzyme B12 [15••]. Because these two ligands can independently repress metE expression, the tandem riboswitch arrangement is proposed to function as a Boolean NOR gate that inhibits the production of the MetE protein whenever S-adenosylmethionine or coenzyme B12 are present [15••]. The ability to control metE expression in response to these two metabolites is conserved in E. coli, but through the traditional’ protein binding to S-adenosylmethionine and coenzyme B12. In addition, the Breaker laboratory reports the results of a genomic analysis predicting the existence of other mRNAs with tandem riboswitches, some of which are suggested to respond to different undefined ligands. These results indicate that extant bacterial species often rely on sophisticated RNA-based sensors to integrate multiple signals into the decision to express particular gene products, which had been the province of protein full articleURL microbiota A new force in diagnosing and treating pancreatic cancerZhengting Jiang, ... Dong Tang, in Cancer Letters, Intratumoral microbiota as a potential biomarker for pancreatic cancer diagnosisA significant difference was observed in the abundance of microbiota between healthy tissues and pancreatic tumors Table 1. 16S rRNA gene sequencing of some microbiota associated with pancreatic cancer revealed that Enterobacteriaceae, Pseudomonadaceae, Proteobacteria, Bacteroidetes, Firmicutes, Pseudoxanthomonas, Streptomyces, Saccharopolyspora and Bacillus clausii were significantly more abundant in pancreatic tumors, while the abundance of some other microbiota only changed outside of the tumor. This demonstrates that intratumoral microbiota may be a biomarker for the diagnosis of pancreatic cancer, and changes in intratumoral microbiota may play a vital role in the timely detection of pancreatic cancer and prediction of prognosis [56].Table 1. Changes in the abundance of microbiota in patients with pancreatic typeMicrobial characterizationAbundance changes outside the tumorAbundance changes in the tumorReferencesEnterobacteriaceae, PseudomonadaceaePancreatic tumors16S rRNA gene sequencingincreasingincreasing[7]Proteobacteria, Bacteroidetes, FirmicutesPancreatic tumors16S rRNA gene sequencingincreasingincreasing[8]Pseudoxanthomonas, Streptomyces, Saccharopolyspora, Bacillus clausiiPancreatic tumors16S rRNA gene sequencingincreasingincreasing[10]Proteobacteria, Actinobacteria, Fusobacteria, VerrucomicrobiaFecal16S rRNA gene sequencingincreasing[8]Porphyromonas, Aggregatibacter, Porphyromonas gingivalisSalivary16S rRNA gene sequencingincreasing[59]Leptotrichia, Fusobacteria, Porphyromonas, Streptococcus mitis, Neisseria elongateSalivary16S rRNA gene sequencingdecreasing[59]Table 2. Clinical trials of microbiota-associated pancreatic NumberTitleStatusConditionsInterventionsNCT03809247Microbial Diversity of Pancreatic DiseasesRecruitingPancreatic CancerPancreatic DiseaseNCT03840460A Prospective Translational Tissue Collection Study in Early and Advanced Pancreatic Ductal Adenocarcinoma and Pancreatic Neuroendocrine Tumors to Enable Further Disease Characterization and the Development of Potential Predictive and Prognostic BiomarkersRecruitingPancreatic AdenocarcinomaNCT04203459The Mechanism of Enhancing the Anti-tumor Effects of CAR-T on PC by Gut Microbiota RegulationRecruitingPancreatic CancerGut MicrobiotaCAR-TNCT04600154MS-20 on Gut Microbiota and Risk/Severity of Cachexia in Pancreatic Cancer PatientsRecruitingPancreatic CancerDrug MS-20CachexiaOther PlaceboChemotherapy EffectNCT04931069Correlation Between Complications After Pancreaticoduodenectomy and MicrobiotaRecruitingPancreatic CancerOther Microbiota analysisNCT04975217Fecal Microbial Transplants for the Treatment of Pancreatic CancerRecruitingPancreatic Ductal AdenocarcinomaProcedure Fecal Microbiota TransplantationDrug Fecal Microbiota Transplantation CapsuleOther Questionnaire Administration and 2 more …NCT04993846Pancreatic Cancer and Oral MicrobiomeRecruitingOral MicrobiomeDiagnostic Test Dental plaque samplingPancreatic CancerIPMNDiagnostic Test qPCRParodontopathyNCT05193162Retrospective Study on Microbial Diversity in Paraffin Tissue of Pancreatic DiseasesRecruitingPancreatic CancerOther No any interventionPancreatic DiseaseMicrobial ColonizationNCT05271344Oral Immunonutrition With Synbiotics, Omega 3 and Vitamin D in Patients Undergoing Duodenopancreatectomy for Tumoral LesionRecruitingPancreatic CancerDietary Supplement Nutritional ProductsComplication, PostoperativeSurgery1Intratumoral microbiota is used for the early detection of pancreatic cancer. The intestinal tract, oral cavity, and NAT are the primary potential sources of the intratumoral microbiota. Of these, oral microbiota derived from saliva samples are the most readily available and are used as biomarkers for noninvasive detection [57]. Compared to healthy controls, in pancreatic cancer patients, the salivary levels of Porphyromonas, Leptrichina, Streptococcus and Leptospira significantly increased, while the levels of Neisseria and Veillonella decreased [58]. Using 16S rRNA sequencing of saliva samples from 361 pancreatic adenocarcinomas and 371 matched controls, the researchers found that Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis can increase the risk of pancreatic cancer and Fusobacteria and its genus Leptotrichia decreased this risk [59]. Additionally, Neisseria mucosa and Fusobacterium periodonticum are associated with a risk of developing pancreatic cancer [60]. Therefore, intratumoral microbiota originating from the oral cavity may be a critical target for the early diagnosis of pancreatic cancer. However, not all oral microbiota can translocate into pancreatic tumors, and the link between changes in the oral microbiota and pancreatic tumor microbiota requires further investigation. Moreover, the abundance of Actinobacteria, Proteobacteria and Firmicutes and the levels of their metabolites including acetate and butyrate in the feces of pancreatic cancer patients were significantly lower than those in normal people. This was demonstrated to be the basis for the early detection of pancreatic cancer [61]. The microbiota in feces originates from the intestinal tract, which is also a potential microbiota source in pancreatic tumors, and the development of pancreatic cancer causes changes in the gut microbiota to manifest in feces [62]. Further investigation is required to determine whether changes in intratumoral microbiota can be demonstrated by detecting microbiota in feces and using this as a potential biomarker for diagnosing pancreatic cancer. Notably, the accuracy of oral and fecal microbiota as diagnostic markers for detecting pancreatic cancer is yet to be assessed [63]. Intratumoral microbiota may have higher accuracy in the timely detection of pancreatic microbiota is used to determine the prognosis of pancreatic cancer patients. Using 16SrRNA sequencing to compare DNA samples from pancreatic cancer patients with different survival outcomes, long-term survivors with an overall survival rate of over five years contained a richer variety of intratumoral microbiota than short-term survivors [10]. Among them, Bacillus clausii, Saccharopolyspora, Streptomyces and Pseudoxanthomonas are strongly associated with the long-term survival of patients, and the abundance of these bacteria is upregulated in long-term survivors [10]. Compared with healthy controls, the abundance of Fusobacterium is significantly increased in pancreatic tumors, which correlates with a shorter survival time in patients [64]. The convincing power of this experiment would be further enhanced if the abundance of Fusobacterium in pancreatic tumors of long-term survivors were compared with that of short-term survivors. These data suggest that intratumoral microbiota acts as a potential biomarker for determining the prognostic status of pancreatic cancer. Intratumoral microbiota is potentially valuable for increasing the accuracy and convenience of prognostic screening in patients with pancreatic full articleURL Tumour immunology April 2021Kathy D McCoy, Lukas F Mager, in Current Opinion in Immunology, 2021Pancreatic cancerUnderstanding the impact of the microbiome in pancreatic ductal adenocarcinoma PDAC is still emerging; however, associations between distinct bacteria such as Porphyromonas gingivalis or Fusobacterium spp. and PDAC have been reported reviewed in Ref. [22]. Recent efforts have focused on identifying specific microbes and microbial signatures that are associated with long term survival LTS compared to short term survival STS in PDAC. Analysis of the tumor microbiome in PDAC revealed a signature of bacteria Pseudoxanthomonas–Streptomyces–Saccharopolyspora–Bacillus clausii found to be enriched in LTS [23•]. Faecal microbial transfer FMT from LTS patients into tumor bearing mice was able to reduce tumor burden and enhance intratumoral CD8+IFN-γ+ T cells when compared to FMT from STS patients. This was remarkable as comparison of matched donor samples revealed that only 25% of the tumor microbiome was represented in the fecal microbiome and only 40% of the transplanted microbiome engrafted into the mice [23•]. This may indicate that a select few bacteria are sufficient to induce anti-tumor immunity in similar study also found marked microbial differences in pancreatic tumors compared to normal pancreatic tissue, with specific enrichment of Actinobacteria, Deferribacteres and Bifidobacteria in tumors [24]. Intriguingly, ablation of the microbiome protected mice from PDAC through reduction of suppressive myeloid cell infiltration and an increase in Th1 activated CD4+ and CD8+ T cells. In contrast to the previous report, FMT from tumor-bearing hosts enhanced PDAC development in recipient mice [24].It is currently unclear as to why these studies report conflicting outcomes. It may merely be based on the stratification of LTS compared to STS microbiomes or different experimental setups. Certainly, the tumor-associated microbiome in the pancreas modulates PDAC development, but the precise dissection of host–microbiome interactions awaits further full articleURL

bacillus subtilis và bacillus clausii