Enterococcus faecium SF68 as a model for efficacy and safety evaluation of pharmaceutical probiotics.
Holzapfel W,Arini A,Aeschbacher M,Coppolecchia R,Pot B
Beneficial microbes
As normal inhabitants of diverse ecosystems, including the human gastrointestinal tract, the enterococci, and especially the two species Enterococcus faecalis and Enterococcus faecium, can be considered ubiquitous with regard to our natural environment. E. faecium has gained special importance thanks to beneficial strains marketed as probiotics, and because of its beneficial role in traditional fermented foods such as artisanal cheeses in some Southern European countries. Yet, following reports on the increasing association of some enterococcal strains with nosocomial infections such as endocarditis and bacteraemia, it became evident that strains from clinical origin are frequently highly resistant to 'last-defence-line' antibiotics such as the glycopeptide derivatives. For this reason enterococci have been classified in risk group 2 in the European Directive 93/88. With this paper it is intended to clarify the uncertain situation around the safety of the species E. faecium, also with referring to intra-species heterogeneity. In fact, well established scientific and surveillance data support the safety of some probiotic E. faecium strains for both human and animal applications. As a model, summarising yet extensive information is provided on the efficacy and safety of E. faecium SF68®, a pharmaceutical probiotic with a long history of safe use. We propose the approach presented in this review as a model for the evaluation of safety of probiotic strains of this species.
10.3920/BM2017.0148
Protective role of gamma-aminobutyric acid against chronic renal failure in rats.
Sasaki Sumiyo,Yokozawa Takako,Cho Eun Ju,Oowada Shigeru,Kim Mujo
The Journal of pharmacy and pharmacology
The protective effect of gamma-aminobutyric acid (GABA) against chronic renal failure (CRF) was investigated using a remnant kidney model with 5/6 nephrectomized rats. Nephrectomy led to renal dysfunction, which was evaluated via several parameters including serum urea nitrogen, creatinine (Cr) and Cr clearance. However, the administration of GABA ameliorated renal dysfunction, and a longer administration period of GABA increased its protective effect. In addition, nephrectomized control rats showed an elevation in the fractional excretion of sodium (FE(Na)) with an increase in urinary sodium, while GABA led to a significant decline in FE(Na). Moreover, nephrectomy resulted in a decrease of serum albumin and an increase of urinary protein with a change in the urinary protein pattern, whereas the rats administered GABA showed improvement in these changes associated with CRF caused by nephrectomy. This suggests that GABA would inhibit the disease progression and have a protective role against CRF. As one of the risk factors for CRF progression, hypertension was also regulated by GABA. The results also indicate that GABA may play a protective role against CRF through improvement of the serum lipid profile, with reductions in triglyceride and total cholesterol. Furthermore, nephrectomy led to renal oxidative stress with a decrease in the activity of antioxidative enzymes and elevation of lipid peroxidation. The administration of GABA attenuated oxidative stress induced by nephrectomy through an increase in superoxide dismutase and catalase, and decrease in lipid peroxidation. The histopathological lesions, including glomerular, tubular and interstitial lesions, under nephrectomy were also improved by GABA with the inhibition of fibronectin expression. This study demonstrated that GABA attenuated renal dysfunction via regulation of blood pressure and lipid profile, and it also ameliorated the oxidative stress induced by nephrectomy, suggesting the promising potential of GABA in protecting against renal failure progression.
10.1211/jpp.58.11.0013
Minocycline ameliorates anxiety-related self-grooming behaviors and alters hippocampal neuroinflammation, GABA and serum cholesterol levels in female Sprague-Dawley rats subjected to chronic unpredictable mild stress.
Zhang Cai,Kalueff Allan V,Song Cai
Behavioural brain research
Neuroinflammation induced by stress results in aberrant neurotransmission and dyslipidemia, which can trigger depression- and anxiety-like behaviors. Gamma-aminobutyric acid (GABA) and cholesterol play a crucial role in anxiety-like states, including self-grooming - a common stress-evoked rodent behavior. However, the interaction between neuroinflammation, GABA and cholesterol under stress, and their effects on grooming, remain unclear. Here, we utilize the chronic unpredictable mild stress (CUMS) rat cohort used previously in our Zhang et al. (2019) study, to examine whether CUMS affects grooming behavior, and whether minocycline, a microglia antagonist, can correct these behavioral deficits, accompanied by altering hippocampal neuroinflammation, GABA and serum cholesterol levels. Female Sprague-Dawley rats underwent a 6-week CUMS and received daily minocycline (40 mg/kg, i.p.) during this period, followed by behavioral testing in the open field test. Serum cholesterol, inflammatory cytokines and GABA levels in hippocampus were assayed by ELISA. CUMS significantly decreased locomotion, rearing, central zone entries and time spent in the open field center compared to unstressed controls. CUMS also strongly affected self-grooming behaviors, increasing the frequency of grooming episodes, the number of transitions, interruptions and individual elements of various grooming phases. However, these CUMS-induced behavioral abnormalities were corrected by minocycline. Likewise, CUMS elevated total serum cholesterol and lowered serum high-density lipoprotein cholesterol, whereas minocycline ameliorated these responses. CUMS also lowered hippocampal GABA, whereas minocycline normalized CUMS-induced GABA in the hippocampus. We also found significant correlations between neuroinflammation and GABA, neuroinflammation and cholesterol, GABA and grooming, as well as cholesterol and grooming measures, further implicating stress-evoked neuroinflammation, GABA and cholesterol in the regulation of complex rodent behaviors. In summary, minocycline ameliorated CUMS-induced aberrant self-grooming behaviors in rats by altering hippocampal neuroinflammation, GABA and serum cholesterol levels.
10.1016/j.bbr.2019.01.045
Gamma-aminobutyric acid-producing lactobacilli positively affect metabolism and depressive-like behaviour in a mouse model of metabolic syndrome.
Patterson E,Ryan P M,Wiley N,Carafa I,Sherwin E,Moloney G,Franciosi E,Mandal R,Wishart D S,Tuohy K,Ross R P,Cryan J F,Dinan T G,Stanton C
Scientific reports
Metabolic and neuroactive metabolite production represents one of the mechanisms through which the gut microbiota can impact health. One such metabolite, gamma-aminobutyric acid (GABA), can modulate glucose homeostasis and alter behavioural patterns in the host. We previously demonstrated that oral administration of GABA-producing Lactobacillus brevis DPC6108 has the potential to increase levels of circulating insulin in healthy rats. Therefore, the objective of this study was to assess the efficacy of endogenous microbial GABA production in improving metabolic and behavioural outcomes in a mouse model of metabolic dysfunction. Diet-induced obese and metabolically dysfunctional mice received one of two GABA-producing strains, L. brevis DPC6108 or L. brevis DSM32386, daily for 12 weeks. After 8 and 10 weeks of intervention, the behavioural and metabolic profiles of the mice were respectively assessed. Intervention with both L. brevis strains attenuated several abnormalities associated with metabolic dysfunction, causing a reduction in the accumulation of mesenteric adipose tissue, increased insulin secretion following glucose challenge, improved plasma cholesterol clearance and reduced despair-like behaviour and basal corticosterone production during the forced swim test. Taken together, this exploratory dataset indicates that intervention with GABA-producing lactobacilli has the potential to improve metabolic and depressive- like behavioural abnormalities associated with metabolic syndrome in mice.
10.1038/s41598-019-51781-x
Effects of Lactobacillus acidophilus and Bifidobacterium bifidum Probiotics on the Expression of MicroRNAs 135b, 26b, 18a and 155, and Their Involving Genes in Mice Colon Cancer.
Heydari Zahra,Rahaie Mahdi,Alizadeh Ali Mohammad,Agah Shahram,Khalighfard Solmaz,Bahmani Sahar
Probiotics and antimicrobial proteins
A wide range of sources supports that the link between diet and colorectal cancer may be due to an imbalance of the intestinal microflora. In this case, it seems that the probiotics may have a possible molecular mechanism via microRNAs (miRNAs). The present study is aimed to evaluate the effects of Lactobacillus acidophilus and Bifidobacterium bifidum probiotics on the expression of miRNAs 135b, 26b, 18a, and 155 and their target genes, including APC, PTEN, KRAS, and PU.1 in mouse azoxymethane (AOM)-induced colon cancer. Thirty-eight male BALB/c mice were randomly divided into four groups: the control, AOM, Lactobacillus acidophilus, and Bifidobacterium bifidum to deliberate the effects of the probiotics on the miRNAs and their target genes. Except for the control group, the rest groups were weekly given AOM (15 mg/kg, s.c) in three consecutive weeks to induce mouse colon cancer. The animals were given 1.5 g powders of L. acidophilus (1 × 10 cfu/g) and B. bifidum (1 × 10 cfu/g) in 30 cc drinking water in the related groups for 5 months. At the end of the study, the animals were sacrificed and their blood and colon samples were removed for the molecular analyses. The results showed that the expression of the miR-135b, miR-155, and KRAS was increased in the AOM group compared to the control group in both the plasma and the colon tissue samples, and the consumption of the probiotics decreased their expression. Moreover, the miR-26b, miR-18a, APC, PU.1, and PTEN expressions were decreased in the AOM group compared to the control group and the consumption of the probiotics increased their expressions. It seems that Lactobacillus acidophilus and Bifidobacterium bifidum though increasing the expression of the tumor suppressor miRNAs and their target genes and decreasing the oncogenes can improve colon cancer treatment.
10.1007/s12602-018-9478-8
A combination of calcium phosphate and probiotics beneficially influences intestinal lactobacilli and cholesterol metabolism in humans.
Trautvetter Ulrike,Ditscheid Bianka,Kiehntopf Michael,Jahreis Gerhard
Clinical nutrition (Edinburgh, Scotland)
BACKGROUND & AIMS:The study focuses on the influence of a probiotic supplement alone and in combination with a calcium supplement on faecal lactobacilli colonisation and beneficial health effects such as a lowering of blood cholesterol. METHODS:Thirty-two men and women participated in the double-blind, placebo-controlled, cross-over study. All participants consumed a probiotic drink containing 10(10)CFU/d Lactobacillus paracasei (LPC37) for four weeks. In addition, one group consumed bread enriched with pentacalcium hydroxy-triphosphate (CaP; 1g Ca/d) and the other group had bread without CaP. After a two-week washout and a two-week placebo period, the intervention was switched for further four weeks. RESULTS:After intervention with LPC37+CaP, total cholesterol and LDL-cholesterol concentration in plasma decreased significantly compared to LPC37 and placebo. The faecal concentration of L. paracasei and that of all lactobacilli increased significantly after LPC37+CaP and LPC37 compared to placebo. Moreover, secondary bile acids in faeces increased significantly after LPC37+CaP intervention compared to placebo. CONCLUSIONS:CaP modulates the colonisation of LPC37 in the human gut under combinatory supplementation of CaP and LPC37. The combined supplementation also decreases plasma LDL-cholesterol and the LDL/HDL ratio in healthy, moderately hypercholesterolemic men and women, which could be also due to the CaP supplementation. CLINICAL TRIAL REGISTRATION NUMBER:NCT01033461.
10.1016/j.clnu.2011.09.013
Lactobacillus plantarum strains as potential probiotic cultures with cholesterol-lowering activity.
Huang Ying,Wang Xiaojun,Wang Jinfeng,Wu Fei,Sui Yujie,Yang Longfei,Wang Zonggui
Journal of dairy science
Elevated blood cholesterol is an important risk factor associated with atherosclerosis and coronary heart disease. The search for mediators that fine-tune cholesterol homeostasis has revealed lactic acid bacteria (LAB) to be potentially beneficial. The aim of the present study was to identify and characterize probiotic strains with bile salt hydrolase activity from kefir grains and evaluate their potential use as cholesterol-reducing probiotics in rats. Two isolates, Lp09 and Lp45, obtained from kefir grains were identified as Lactobacillus plantarum via molecular typing methods. Lactobacillus plantarum Lp09 and Lp45 exhibited excellent tolerance to low pH levels and high bile salt concentrations and showed potential bile salt hydrolase activity, bile salt deconjugation activity, and cholesterol coprecipitation ability. Additionally, the potential effect of Lb. plantarum Lp09 and Lp45 on plasma cholesterol levels was evaluated in Sprague-Dawley rats. Rats in 3 treatment groups were fed different experimental diets: a high-cholesterol diet, a high-cholesterol diet plus Lb. plantarum Lp09, or a high-cholesterol diet plus Lb. plantarum Lp45 for 4 wk. Total cholesterol, triglyceride, and low-density lipoprotein cholesterol levels in serum as well as cholesterol and triglyceride levels in liver were significantly decreased in the LAB-treated rats compared with rats fed a high-cholesterol diet without LAB supplementation. Also, both fecal cholesterol and bile acid levels were significantly increased after LAB administration. No significant changes were detected in high-density lipoprotein cholesterol levels. These results suggest that the Lb. plantarum Lp09 and Lp45 strains present the potential to be explored as probiotic agents for the management of hypercholesterolemia.
10.3168/jds.2012-6123
Cholesterol-lowering potentials of Lactobacillus strain overexpression of bile salt hydrolase on high cholesterol diet-induced hypercholesterolemic mice.
Wang Guangqiang,Huang Wenli,Xia Yongjun,Xiong Zhiqiang,Ai Lianzhong
Food & function
Hypercholesterolemia is closely associated with cardiovascular disease. Supplementation with probiotics has been shown to contribute to improving lipid metabolism. The probiotic mechanisms of cholesterol reduction are complicated and remain unclear. One of the potential probiotic mechanisms for cholesterol reduction is the deconjugation of bile salts. We previously found a high bile salt hydrolase (BSH) activity of Lactobacillus casei pWQH01 (overexpression of bsh1) and Lactobacillus plantarum AR113, but found no BSH activity for Lactobacillus casei LC2W in vitro. Therefore, we decided to investigate whether the high BSH activity of L. plantarum AR113 and L. casei pWQH01 could exert a cholesterol-reducing effect in vivo. Compared to the high-cholesterol diet (HCD) group, AR113 and pWQH01 groups had a significantly lower body weight (BW), serum total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) levels and atherogenic index (AI), whereas the LC2W group had a poor capability to mitigate the blood lipid levels in the hypercholesterolemic mice. In addition, the AR113 and pWQH01 groups decreased the hepatic levels of TC and LDL-C and improved hepatic steatosis compared with the HCD group. To explore their cholesterol-lowering mechanisms of action, we determined the expression levels of these genes on the cholesterol metabolic pathways. AR113 and pWQH01 groups downregulated the expression of farnesoid X receptor (FXR) and small heterodimer partner (SHP) genes, but upregulated the expression of the cholesterol 7α-hydroxylase (CYP7A1) gene in the liver. Simultaneously, the expression of cholesterol liver X receptor (LXR) and low density lipoprotein receptor (LDLR) genes was upregulated in the liver. These results indicated that L. plantarum AR113 and L. casei pWQH01 could inhibit the cholesterol absorption and accelerate the cholesterol transportation. Taken together, these findings suggest that Lactobacillus strain overexpression of bile salt hydrolase has beneficial effects against hypercholesterolemia by reducing cholesterol absorption and increasing cholesterol catabolism.
10.1039/c8fo02181c
Lactobacillus fermentum NCIMB 5221 and NCIMB 2797 as cholesterol-lowering probiotic biotherapeutics: in vitro analysis.
Tomaro-Duchesneau C,Saha S,Malhotra M,Jones M L,Rodes L,Prakash S
Beneficial microbes
Cardiovascular and coronary artery disease risk are correlated with cholesterol levels and are significant health concerns. Current cholesterol-lowering approaches includes lifestyle and diet modifications, as well as statins which presents numerous shortcomings. The probiotic bacteria, Lactobacillus fermentum NCIMB 5221 and NCIMB 2797, have demonstrated cholesterol-lowering potential in animal studies. However, there is a lack in understanding the mechanism(s) behind these observed effects. The goal of this work is to investigate, in vitro, the cholesterol-lowering mechanisms of these two strains. To determine the cholesterol-lowering mechanisms, probiotic cholesterol assimilation, colon epithelial adhesion and inhibition of cholesterol uptake by colon epithelial (Caco-2) cells were investigated. L. fermentum NCIMB 2797 (P=0.012) and NCIMB 5221 (P=0.003) assimilated cholesterol and their cell surface hydrophobicity was 70.30±8.85% and 55.60±2.59%, respectively. Both L. fermentum strains showed no significant impact (P>0.05) on Caco-2 cell viability. Of most interest, Caco-2 pre-exposure to L. fermentum NCIMB 5221 significantly decreased (P=0.015) cholesterol uptake, with 85.98±2.07% uptake compared to the untreated cells. Similarly, L. fermentum NCIMB 2797 probiotic cells significantly decreased (P=0.019) cholesterol uptake by Caco-2 cells, with 86.45±1.71% uptake observed compared to the control cells. The results demonstrate that L. fermentum NCIMB 5221 and L. fermentum NCIMB 2797 have the potential via various modes of action to lower cholesterol. Additional studies are required to understand the mechanism(s) of action behind probiotic cholesterol assimilation and behind the cholesterol uptake inhibition by colon epithelial cells.
10.3920/BM2015.0021
Lactic acid bacteria with cholesterol-lowering properties for dairy applications: In vitro and in situ activity.
Albano C,Morandi S,Silvetti T,Casiraghi M C,Manini F,Brasca M
Journal of dairy science
Cholesterol-lowering activity is one of the most promising properties of lactic acid bacteria with probiotic characteristics. In the present study, 58 potentially probiotic lactic acid bacteria were tested for their ability to survive in vitro digestion and reduce cholesterol in a medium containing cholesterol and bile acids. The best-performing strains (Lactobacillus casei VC199, Lactobacillus paracasei ssp. paracasei SE160 and VC213, Lactobacillus plantarum VS166 and VS513, Enterococcus faecium VC223, and Enterococcus lactis BT161) resulted in a 42 to 55% reduction of the cholesterol level in broth and were further tested in cheese manufacture. The cholesterol content in all the cheeses decreased with ripening. All the strains were present in the cheese at levels higher than 10 cfu/g until 60 d of ripening, the highest reductions (up to 23%) being obtained when Lb. paracasei ssp. paracasei VC213 and E. lactis BT161 were added during the cheese-making. The adjunct cultures had no negative effect on the sensory characteristics of the cheese. Thus, these strains with proven in vitro properties are good candidates for novel probiotic-containing formulations and could be used to functionalize foods such as dairy fermented products.
10.3168/jds.2018-15096
Cholesterol-lowering probiotics: in vitro selection and in vivo testing of bifidobacteria.
Bordoni Alessandra,Amaretti Alberto,Leonardi Alan,Boschetti Elisa,Danesi Francesca,Matteuzzi Diego,Roncaglia Lucia,Raimondi Stefano,Rossi Maddalena
Applied microbiology and biotechnology
Thirty-four strains of bifidobacteria belonging to Bifidobacterium adolescentis, Bifidobacterium animalis, Bifidobacterium bifidum, Bifidobacterium breve, Bifidobacterium longum, and Bifidobacterium pseu-docatenulatum were assayed in vitro for the ability to assimilate cholesterol and for bile salt hydrolase (BSH) against glycocholic and taurodeoxycholic acids (GCA and TDCA). Cholesterol assimilation was peculiar characteristic of two strains belonging to the species B. bifidum (B. bifidum MB 107 and B. bifidum MB 109), which removed 81 and 50 mg of cholesterol per gram of biomass, being the median of specific cholesterol absorption by bifidobacteria 19 mg/g. Significant differences in BSH activities were not established among bifidobacterial species. However, the screening resulted in the selection of promising strains able to efficiently deconjugate GCA and TDCA. No relationship was recognized between BSH phenotype and the extent of cholesterol assimilation. On the basis of cholesterol assimilation or BSHGCA and BSHTDCA activities, B. bifidum MB 109 (DSMZ 23731), B. breve MB 113 (DSMZ 23732), and B. animalis subsp. lactis MB 2409 (DSMZ 23733) were combined in a probiotic mixture to be fed to hypercholesterolemic rats. The administration of this probiotic formulation resulted in a significant reduction of total cholesterol and low-density cholesterol (LDL-C), whereas it did not affect high-density cholesterol (HDL-C) and HDL-C/LDL-C ratio.
10.1007/s00253-013-5088-2
Effect of Probiotics Bacillus coagulans and Lactobacillus plantarum on Lipid Profile and Feces Bacteria of Rats Fed Cholesterol-Enriched Diet.
Aminlari Ladan,Shekarforoush Seyed Shahram,Hosseinzadeh Saeid,Nazifi Saeed,Sajedianfard Javad,Eskandari Mohammad Hadi
Probiotics and antimicrobial proteins
The aim of this study was to investigate the effect of Lactobacillus plantarum and Bacillus coagulans on serum lipid profile and lowering potential of probiotic in hypercholesterolemic rats. Twenty-eight male Wistar rats were divided into four groups as follows: (1) control group, fed standard commercial diet; (2) HC group, fed high-cholesterol diet; (3) HC + LP group, fed high-cholesterol diet and gavaging of L. plantarum; and (4) HC + BC group fed high-cholesterol diet and gavaging of B. coagulans. After 28 and 50 days, serum lipid profile; serum ALT and AST; the body and organ weights; fecal total count; Enterobacteriaceae, L. plantarum, and B. coagulans counts; and blood glucose tolerance were measured. We observed that levels of triglyceride, cholesterol, LDL, VLDL, and atherogenic index in serum were significantly lower in the HC + probiotic groups. Also, serum ALT and AST were significantly decreased in probiotic-treated groups. In addition, we found that feeding of a high-cholesterol diet for 50 days produced significant increases in the body weight, in addition to the fact that the administration of L. plantarum and B. coagulans has considerably reduced the body weight gain. B. coagulans and L. plantarum can survive passing through the upper-gastrointestinal tract after oral feeding to the rats and colonized in their colon. These bacteria could be exploited as a potential biotherapeutic remedy to reduce TC, TG, LDL, VLDL, and atherogenic index in hypercholesterolemic condition.
10.1007/s12602-018-9480-1
Characterization of Selected Lactobacillus Strains for Use as Probiotics.
Song Minyu,Yun Bohyun,Moon Jae-Hak,Park Dong-June,Lim Kwangsei,Oh Sejong
Korean journal for food science of animal resources
The aim of this study was to evaluate the functional properties of lactic acid bacteria from various sources and to identify strains for use as probiotics. Ten Lactobacillus strains were selected and their properties such as bile tolerance, acid resistance, cholesterol assimilation activity, and adherence to HT-29 cells were assessed to determine their potential as probiotics. Lactobacillus sp. JNU 8829, L. casei MB3, L. sakei MA9, L. sakei CH8, and L. acidophilus M23 were found to show full tolerance to the 0.3% bile acid. All strains without L. acidophilus M23 were the most acid-tolerant strains. After incubating the strains at pH 2.5 for 2 h, their viability decreased by 3 Log cells. Some strains survived at pH 2.5 in the presence of pepsin and 0.3% bile acid. Lactobacillus sp. JNU 8829, L. acidophilus KU41, L. acidophilus M23, L. fermentum NS2, L. plantarum M13, and L. plantarum NS3 were found to reduce cholesterol levels by >50% in vitro. In the adhesion assay, Lactobacillus sp. JNU 8829, L. casei MB3, L. sakei MA9, and L. sakei CH8 showed higher adhesion activities after 2 h of co-incubation with the intestinal cells. The results of this comprehensive analysis shows that this new probiotic strain named, Lactobacillus sp. JNU 8829 could be a promising candidate for dairy products.
10.5851/kosfa.2015.35.4.551
Antagonistic effects of Streptococcus and Lactobacillus probiotics in pharyngeal biofilms.
Humphreys G J,McBain A J
Letters in applied microbiology
Direct antagonism towards pathogens including Streptococcus pyogenes is a proposed mechanism of pharyngeal probiosis but off-target effects on the symbiotic microbiota of the throat are possible and may be beneficial, harmful or neutral. We have assessed the bacteriological effects of two candidate Lactobacillus probiotics and the established pharyngeal probiotic Streptococcus salivarius K12. Antagonism towards S. pyogenes and potential off-target effects were determined using sessile monospecies biofilms and pharyngeal microcosms, respectively. The candidate probiotics were antagonistic towards S. pyogenes (rank order of increasing potency, Lactobacillus acidophilus < Lactobacillus plantarum < Streptococcus salivarius) in the absence of significant acidification or cell-cell contact. Streptococcus salivarius and L. plantarum caused significant reductions in viable counts of streptococci in pharyngeal microbiotas, whilst S. salivarius also caused reductions in staphylococci. In contrast, changes in pharyngeal eubacterial DNA profiles were limited overall. In summary, the three candidate probiotics suppressed axenic Streptococcus pyogenes biofilms by mechanisms that did not depend on cell-cell contact or acidification and did not markedly destabilize complex pharyngeal microbiotas derived from healthy individuals. SIGNIFICANCE AND IMPACT OF THE STUDY: Candidate probiotic bacteria deployed to prevent or treat bacterial pharyngitis will interact with the target bacteria such as Streptococcus pyogenes as well as with the microbiota of the throat, where off-target effects are possible. Three candidate probiotics Lactobacillus acidophilus, Lactobacillus plantarum and Streptococcus salivarius reduced viability within extant S. pyogenes biofilms through the elaboration of diffusible factors other than fermentation acids but did not markedly disrupt ex situ pharyngeal microcosms. This work demonstrates the application of in vitro pharyngeal models in the preclinical testing of the safety and efficacy of candidate pharyngeal probiotics.
10.1111/lam.13133
A review on sustainable yeast biotechnological processes and applications.
Nandy Subir Kumar,Srivastava R K
Microbiological research
Yeast is very well known eukaryotic organism for its remarkable biodiversity and extensive industrial applications. Saccharomyces cerevisiae is one of the most widely used microorganisms in biotechnology with successful applications in the biochemical production. Biological conversion with the focus on the different utilization of renewable feedstocks into fuels and chemicals has been intensively investigated due to increasing concerns on sustainability issues worldwide. Compared with its counterparts, Saccharomyces cerevisiae, the baker's yeast, is more industrially relevant due to known genetic and physiological background, the availability of a large collection of genetic tools, the compatibility of high-density and large-scale fermentation, and optimize the pathway for variety of products. Therefore, S. cerevisiae is one of the most popular cell factories and has been successfully used in the modern biotech industry to produce a wide variety of products such as ethanol, organic acids, amino acids, enzymes, and therapeutic proteins. This study explores how different sustainable solutions used to overcome various environmental effects on yeast. This work targets a broad matrix of current advances and future prospect in yeast biotechnology and discusses their application and potential in general.
10.1016/j.micres.2017.11.013
Impact of Saccharomyces cerevisiae metabolites produced during fermentation on bread quality parameters: A review.
Heitmann Mareile,Zannini Emanuele,Arendt Elke
Critical reviews in food science and nutrition
Although bread making with the use of Baker's yeast has a long tradition in human history, little attention has been paid to the connection between yeast addition and the final bread quality. Nowadays, bakers mainly use different flour additives such as enzymes (amylases, hemicellulases, and proteases) to change and improve dough properties and/or bread quality. Another strategy is the use of modified industrial Baker's yeast. To date, there is no yeast strain used in the baking industry, which is genetically modified, despite some studies demonstrating that the application of recombinant DNA technology is a possibility for improved strains suitable for baking. However, due to the fact that the majority of consumers in Europe highly reject the use of genetically modified microorganisms in the production of food, other strategies to improve bread quality must be investigated. Such a strategy would be a reconsideration of the selection of yeast strains used for the baking process. Next to the common criteria, the requirement for adequate gas production, more attention should be paid on how yeast impacts flavor, shelf life, color, and the nutritional value of baked products, in a similar way to which yeast strains are selected in the wine and brewing industries.
10.1080/10408398.2016.1244153
Metabolic regulatory mechanisms and physiological roles of functional amino acids and their applications in yeast.
Takagi Hiroshi
Bioscience, biotechnology, and biochemistry
In yeast, amino acid metabolism and its regulatory mechanisms vary under different growth environments by regulating anabolic and catabolic processes, including uptake and export, and the metabolic styles form a complicated but robust network. There is also crosstalk with various metabolic pathways, products and signal molecules. The elucidation of metabolic regulatory mechanisms and physiological roles is important fundamental research for understanding life phenomenon. In terms of industrial application, the control of amino acid composition and content is expected to contribute to an improvement in productivity, and to add to the value of fermented foods, alcoholic beverages, bioethanol, and other valuable compounds (proteins and amino acids, .). This review article mainly describes our research in constructing yeast strains with high functionality, focused on the metabolic regulatory mechanisms and physiological roles of "functional amino acids", such as l-proline, l-arginine, l-leucine, l-valine, l-cysteine, and l-methionine, found in yeast.
10.1080/09168451.2019.1576500
Probiotic Saccharomyces cerevisiae strains as biotherapeutic tools: is there room for improvement?
Palma Mariana L,Zamith-Miranda Daniel,Martins Flaviano S,Bozza Fernando A,Nimrichter Leonardo,Montero-Lomeli Mônica,Marques Ernesto T A,Douradinha Bruno
Applied microbiology and biotechnology
The probiotic yeast Saccharomyces cerevisiae var boulardii is widely used as a low cost and efficient adjuvant against gastrointestinal tract disorders such as inflammatory bowel disease and treatment of several types of diarrhea, both in humans and animals. S. boulardii exerts its protective mechanisms by binding and neutralizing enteric pathogens or their toxins, by reducing inflammation and by inducing the secretion of sIgA. Although several S. cerevisiae strains have proven probiotic potential in both humans and animals, only S. boulardii is currently licensed for use in humans. Recently, some researchers started using S. boulardii as heterologous protein expression systems. Combined with their probiotic activity, the use of these strains as prophylactic and therapeutic proteins carriers might result in a positive combined effort to fight specific diseases. Here, we provide an overview of the current use of S. cerevisiae strains as probiotics and their mechanisms of action. We also discuss their potential to produce molecules with biotherapeutic application and the advantages and hurdles of this approach. Finally, we suggest future directions and alternatives for which the combined effort of specific immunomodulatory effects of probiotic S. cerevisiae strains and ability to express desired foreign genes would find a practical application.
10.1007/s00253-015-6776-x
Application of Saccharomyces cerevisiae var. boulardii in food processing: a review.
Lazo-Vélez M A,Serna-Saldívar S O,Rosales-Medina M F,Tinoco-Alvear M,Briones-García M
Journal of applied microbiology
Probiotics are increasingly being added to food in order to develop products with health-promoting properties. Particularly, Saccharomyces cereviceae var. boulardii yeast is recently being investigated like a starting-culture for development of functional and probiotic foods. Although the literature is abundant on the beneficial effects of S. boulardii on health, slight information is available on the effects of supplementing this probiotic to food systems. The aim of this paper is to examine the applications of S. boulardii to different food matrices and its implication in food processing (stability, sensorial properties and other technological implications) and the concomitant effects on nutrition and health.
10.1111/jam.14037
An overview of Bacillus proteases: from production to application.
Contesini Fabiano Jares,Melo Ricardo Rodrigues de,Sato Hélia Harumi
Critical reviews in biotechnology
Proteases have a broad range of applications in industrial processes and products and are representative of most worldwide enzyme sales. The genus Bacillus is probably the most important bacterial source of proteases and is capable of producing high yields of neutral and alkaline proteolytic enzymes with remarkable properties, such as high stability towards extreme temperatures, pH, organic solvents, detergents and oxidizing compounds. Therefore, several strategies have been developed for the cost-effective production of Bacillus proteases, including optimization of the fermentation parameters. Moreover, there are many studies on the use of low-cost substrates for submerged and solid state fermentation. Other alternatives include genetic tools such as protein engineering in order to obtain more active and stable proteases and strain engineering to better secrete recombinant proteases from Bacillus through homologous and heterologous protein expression. There has been extensive research on proteases because of the broad number of applications for these enzymes, such as in detergent formulations for the removal of blood stains from fabrics, production of bioactive peptides, food processing, enantioselective reactions, and dehairing of skins. Moreover, many commercial proteases have been characterized and purified from different Bacillus species. Therefore, this review highlights the production, purification, characterization, and application of proteases from a number of Bacillus species.
10.1080/07388551.2017.1354354
Trends in the application of Bacillus in fermented foods.
Current opinion in biotechnology
Bacillus species such as Bacillus subtilis and Bacillus amyloliquefaciens are widely used to produce fermented foods from soybeans and locust beans in Asian and West African countries, respectively. Genomic information for B. subtilis strains isolated from Asian Bacillus-fermented foods (BFFs) has been gathered, and the chemical components of fermented products were defined with metabolomic approaches, facilitating the development of new starter strains and the evaluation of health claims. On the other hand, although advanced studies have been performed for some commercially produced BFFs, home-manufactured products still remain to be characterized in rural areas. In West Africa, the microbial flora of BFFs was examined in detail, leading to the isolation of candidates of the starter that produced bacteriocin against Bacillus cereus contaminating the products. These studies may provide a choice of Bacillus strains in food application and increase opportunities for further usage of Bacillus in foods.
10.1016/j.copbio.2018.09.001
[Hypercholesterolemia - Where are we today? Where are we going?].
Gitt A K,Zahn R
Herz
Hypercholesterolemia is one of the major modifiable risk factors for the development of atherosclerosis. Increasing LDL cholesterol is associated with an increased risk of developing cardiovascular diseases as well as cardiovascular ischemic complications. Studies with statins and ultimately with ezetimibe have been able to impressively demonstrate that lowering LDL cholesterol contributes to a significant reduction of cardiovascular ischemic complications.Based on the results of randomized trials for lipid lowering, the practice guidelines developed by the professional societies have defined LDL cholesterol goals. High-risk patients, such as patients with clinically manifest cardiovascular disease, type 2 diabetes, type 1 diabetes with organ damage, moderate or severe chronic kidney disease or a risk of SCORE ≥10 %, should reach LDL cholesterol values <70 mg/dl. Data from observational trials demonstrated that in daily practice only about 20 % of treated high-risk patients reached this recommended LDL cholesterol goal. The therapeutic options are not yet exhausted; patients are treated mainly with low or at most average statin dosages. There should be more potent and high-dose statins used as well as the combination therapy of statin and ezetimibe to achieve the recommended LDL cholesterol goals. Specific cardiac rehabilitation and prevention programs with regular benchmarking could support improved goal-achievement. The new therapeutic option of PCSK9 inhibitors, which significantly and safely lower LDL cholesterol on top of statins and ezetimibe, is currently investigated in large randomized outcome trials.
10.1007/s00059-016-4457-x
Exploitation of Bacillus subtilis as a robust workhorse for production of heterologous proteins and beyond.
Cui Wenjing,Han Laichuang,Suo Feiya,Liu Zhongmei,Zhou Li,Zhou Zhemin
World journal of microbiology & biotechnology
Bacillus subtilis, belonging to the type species of Bacillus, is a type of soil-derived, low %G+C, endospore-forming Gram-positive bacterium. After the discovery of B. subtilis 168 that displayed natural competence, this bacterium has been intensively considered to be an ideal model organism and a robust host to study several basic mechanisms, such as metabolism, gene regulation, bacterial differentiation, and application for industrial purposes, such as heterologous protein expression and the overproduction of an array of bioactive molecules. Since the first report of heterologous overproduction of recombinant proteins in this strain, the bulk production of a multitude of valuable enzymes, especially industrial enzymes, has been performed on a relatively large scale. Since B. subtilis can non-specifically secrete recombinant proteins using various signal peptides, it has tremendous advantages over Gram-negative bacterial hosts. Along with the report of the complete genome sequence of B. subtilis, a number of genetic tools, including diverse types of plasmids, bacterial promoters, regulatory elements, and signal peptides, have been developed and characterized. These novel genetic elements tremendously accelerated genetic engineering in B. subtilis recombinant systems. In addition, with the development of several complex gene expression systems, B. subtilis has performed a number of more complex functions. This ability enables it to be a substantial chassis in synthetic biology rather than just a workhorse for the overproduction of recombinant proteins. In this review, we review the progress in the development of B. subtilis as a universal platform to overproduce heterologous diverse high-value enzymes. This progress has occurred from the development of biological parts, including the characterization and utilization of native promoters, the fabrication of synthetic promoters and regulatory elements, and the assembly and optimization of genetic systems. Some important industrial enzymes that have been produced in large quantities in this host are also summarized in this review. Furthermore, the ability of B. subtilis to serve as a cellular tool was also briefly recapitulated and reviewed.
10.1007/s11274-018-2531-7
Inhibitory Effect of Lactic Acid Bacteria on Foodborne Pathogens: A Review.
Journal of food protection
Foodborne pathogens are serious challenges to food safety and public health worldwide. Fermentation is one of many methods that may be used to inactivate and control foodborne pathogens. Many studies have reported that lactic acid bacteria (LAB) can have significant antimicrobial effects. The current review mainly focuses on the antimicrobial activity of LAB, the mechanisms of this activity, competitive growth models, and application of LAB for inhibition of foodborne pathogens.
10.4315/0362-028X.JFP-18-303
The emerging concept of "individualized cholesterol-lowering therapy": A change in paradigm.
Lütjohann Dieter,Stellaard Frans,Mulder Monique T,Sijbrands Eric J G,Weingärtner Oliver
Pharmacology & therapeutics
High LDL-cholesterol concentrations constitute a risk for atherosclerotic cardiovascular disease. By consensus, cholesterol-lowering therapy is initiated with a statin that reduces endogenous cholesterol synthesis, upregulates hepatic LDL receptor activity, increases LDL clearance and lowers LDL-cholesterol concentrations in the bloodstream. The efficacy of statin treatment is dose dependent and achieves a risk reduction of up to 50%. However, a substantial body of evidence suggests that a quarter of statin-treated patients do not respond adequately as a result of low endogenous cholesterol synthesis. In humans fractional cholesterol absorption varies from 20% to 80%. High cholesterol absorbers, which are characterized by a low-to-normal cholesterol synthesis, exhibit poor responsiveness to statin treatment. On the other hand, the cholesterol absorption inhibitor ezetimibe effectively reduces serum cholesterol levels in these patients. On this background, we suggest to "get personal" and individualize cholesterol-lowering therapies, according to the individual's status of cholesterol synthesis and absorption.
10.1016/j.pharmthera.2019.03.004
The Pharmacologic Role and Clinical Utility of PCSK9 Inhibitors for the Treatment of Hypercholesterolemia.
White C Michael
Journal of cardiovascular pharmacology and therapeutics
In addition to monoclonal antibodies against proprotein convertase subtilisin-kexin type 9 (PCSK9), vaccines against PCSK9 and smaller molecule inhibitors as well as RNA inhibitors of PCSK9 production have been created. The monoclonal antibodies against PCSK9 and the PCSK9 RNA inhibitors can reduce low-density lipoproteins (LDLs) by over 50%, non-high-density lipoprotein (HDL) cholesterol and triglycerides, and increasing HDL. Although effective in several homozygous familial hypercholesterolemia patient types, PCSK9 inhibitors does not work in all patient types. Outcome trials show no effects on mortality but do show reductions in atherosclerotic events such as myocardial infarctions, strokes, and need for coronary revascularization. PCSK9 inhibitors have a very attractive safety profile with no significant elevations in measures of muscle or liver damage. The current and more advanced experimental agents all require subcutaneous dosing, and injection site reactions are among the most common adverse events. Therapy for the Food and Drug Administration (FDA) approved agents is markedly expensive, and this is the primary barrier to utilization. However, it is possible to identify patients with a number needed to treat to prevent an atherosclerotic event low enough to render it cost-effective and one such factor is whether or not you require a 50% reduction in LDL in order to achieve your LDL goal.
10.1177/1074248418769040
A review on the application of Bacillus as probiotics in aquaculture.
Kuebutornye Felix K A,Abarike Emmanuel Delwin,Lu Yishan
Fish & shellfish immunology
Probiotics use in aquaculture has gained attention as microbial candidates to maintain the health and the well-being of many aquaculture animals. Among the many microbial candidates, probiotic Bacillus has sporulation capacity that makes them survive harsh environmental conditions, are non-pathogenic and non-toxic when fed to fish, and can produce antimicrobial substances making them more suitable candidates compared to other probiotics. In this review, we discussed the necessity of using the probiotic Bacillus in sustainable aquaculture as a good alternative to improve feed utilization, stress response, immune response and disease resistance, maintenance of tissue integrity, and as well improvement of water quality for sustainable aquaculture. Therefore the findings of current researches about the effects of Bacillus application to improve the culture of aquatic animals for future research and development of Bacillus application in aquaculture have been summarised.
10.1016/j.fsi.2019.02.010
Metabolic engineering and synthetic biology employing Lactococcus lactis and Bacillus subtilis cell factories.
van Tilburg Amanda Y,Cao Haojie,van der Meulen Sjoerd B,Solopova Ana,Kuipers Oscar P
Current opinion in biotechnology
Metabolic engineering and synthetic biology approaches have prospered the field of biotechnology, in which the main focus has been on Escherichia coli and Saccharomyces cerevisiae as microbial workhorses. In more recent years, improving the Gram-positive bacteria Lactococcus lactis and Bacillus subtilis as production hosts has gained increasing attention. This review will demonstrate the different levels at which these bacteria can be engineered and their various application possibilities. For instance, engineered L. lactis strains show great promise for biomedical applications. Moreover, we provide an overview of recent synthetic biology tools that facilitate the use of these two microorganisms even more.
10.1016/j.copbio.2019.01.007
Application of vitamin-producing lactic acid bacteria to treat intestinal inflammatory diseases.
LeBlanc Jean Guy,Levit Romina,Savoy de Giori Graciela,de Moreno de LeBlanc Alejandra
Applied microbiology and biotechnology
Recent studies have shown that inflammatory diseases are becoming more frequent throughout the world. The causes of these disorders are multifactorial and include genetic, immunological, and environmental factors, and intestinal microbiota dysbiosis. The use of beneficial microorganisms has shown to be useful in the prevention and treatment of disorders such as colitis, mucositis, and even colon cancer by their immune-stimulating properties. It has also been shown that certain vitamins, especially riboflavin and folate derivatives, have proven to be helpful in the treatment of these diseases. The application of vitamin-producing lactic acid bacteria, especially strains that produce folate and riboflavin together with immune-stimulating strains, could be used as adjunct treatments in patients suffering from a wide range of inflammatory diseases since they could improve treatment efficiency and prevent undesirable side effects in addition to their nutrition values. In this review, the most up to date information on the current knowledge and uses of vitamin-producing lactic acid bacteria is discussed in order to stimulate further studies in this field.
10.1007/s00253-020-10487-1