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Nutraceutical approach for the management of cardiovascular risk - a combination containing the probiotic Bifidobacterium longum BB536 and red yeast rice extract: results from a randomized, double-blind, placebo-controlled study.
Ruscica, M, Pavanello, C, Gandini, S, Macchi, C, Botta, M, Dall'Orto, D, Del Puppo, M, Bertolotti, M, Bosisio, R, Mombelli, G, et al
Nutrition journal. 2019;18(1):13
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Probiotics have been shown to reduce total cholesterol (TC) and low-density lipoprotein (LDL-C – often called ‘bad’ cholesterol) in people with moderately raised cholesterol levels. A specific strain of probiotic called Bifidobacterium longum BB536, may decrease TC and LDL-C by reducing the reabsorption of cholesterol from the intestine, and, combined with other natural supplements, may be useful to manage high cholesterol in people at low risk of heart disease. This study was conducted to evaluate the effect of a nutraceutical (Lactoflorene Colesterolo®), containing Bifidobacterium longum BB536 (1bn CFUs) combined with red yeast rice (RYR) extract (10 mg/day monacolin K), niacin (16mg) and coenzyme Q10 (20mg) on levels of cholesterol and fats in the blood. This was a 12-week randomised, parallel, double-blind, placebo-controlled study, in which 33 adults at low risk of heart disease were given either the Bifidobacterium combination, or a placebo. Treatment with the Bifidobacterium combination significantly reduced total cholesterol by 16.7%, LDL-C by 25.7%, non-HDL-C by 24% and apolipoprotein-B by 17%. Triglycerides, HDL-C, apolipoprotein AI, lipoprotein (a) and proprotein convertase subtilisin/kexin type 9 (PCSK9) were unchanged. Markers of cholesterol synthesis and absorption suggested that a reduction in the synthesis of cholesterol had occurred without increased absorption of cholesterol. No adverse effects were reported in the study and the compliance rate was high at 97%. The use of nutraceuticals in the prevention of cardiovascular disease, as well as in other areas related to chronic diseases like cancer, is currently expanding.
Abstract
BACKGROUND Probiotics incorporated into dairy products have been shown to reduce total (TC) and LDL cholesterolemia (LDL-C) in subjects with moderate hypercholesterolemia. More specifically, probiotics with high biliary salt hydrolase activity, e.g. Bifidobacterium longum BB536, may decrease TC and LDL-C by lowering intestinal cholesterol reabsorption and, combined with other nutraceuticals, may be useful to manage hypercholesterolemia in subjects with low cardiovascular (CV) risk. This study was conducted to evaluate the efficacy and safety of a nutraceutical combination containing Bifidobacterium longum BB536, red yeast rice (RYR) extract (10 mg/day monacolin K), niacin, coenzyme Q10 (Lactoflorene Colesterolo®). The end-points were changes of lipid CV risk markers (LDL-C, TC, non-HDL-cholesterol (HDL-C), triglycerides (TG), apolipoprotein B (ApoB), HDL-C, apolipoprotein AI (ApoAI), lipoprotein(a) (Lp(a), proprotein convertase subtilisin/kexin type 9 (PCSK9)), and of markers of cholesterol synthesis/absorption. METHODS A 12-week randomized, parallel, double-blind, placebo-controlled study. Thirty-three subjects (18-70 years) in primary CV prevention and low CV risk (SCORE 0-1% in 24 and 2-4% in 9 subjects; LDL-C: 130-200 mg/dL) were randomly allocated to either nutraceutical (N = 16) or placebo (N = 17). RESULTS Twelve-week treatment with the nutraceutical combination, compared to placebo, significantly reduced TC (- 16.7%), LDL-C (- 25.7%), non-HDL-C (- 24%) (all p < 0.0001), apoB (- 17%, p = 0.003). TG, HDL-C, apoAI, Lp(a), PCSK9 were unchanged. Lathosterol:TC ratio was significantly reduced by the nutraceutical combination, while campesterol:TC ratio and sitosterol:TC ratio did not change, suggesting reduction of synthesis without increased absorption of cholesterol. No adverse effects and a 97% compliance were observed. CONCLUSIONS A 12-week treatment with a nutraceutical combination containing the probiotic Bifidobacterium longum BB536 and RYR extract significantly improved the atherogenic lipid profile and was well tolerated by low CV risk subjects. TRIAL REGISTRATION NCT02689934 .
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Disruption of the Gut Ecosystem by Antibiotics.
Yoon, MY, Yoon, SS
Yonsei medical journal. 2018;59(1):4-12
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The gut microbiome is a complex ecosystem of different micro-organisms, such as bacteria, viruses and fungi, living in the human intestines. It’s involved in numerous functions, such as extracting energy and nutrition from food, protecting against disease-causing microorganisms, and supporting the immune system of the host, and therefore affecting human health and disease. This paper is a review of studies on the effects of antibiotics on the gut microbiota. It outlines how different types of antibiotics can alter the intestinal environment and the composition of the microbes, resulting in various physiological changes that can trigger disease. Relevant mechanisms, such as inflammatory response and the use of intestinal nutrients by infectious bacteria are discussed. Finally, it discusses faecal microbiota transplantation (FMT) and probiotics as treatment approaches, aimed at restoring a disturbed intestinal environment.
Abstract
The intestinal microbiota is a complex ecosystem consisting of various microorganisms that expands human genetic repertoire and therefore affects human health and disease. The metabolic processes and signal transduction pathways of the host and intestinal microorganisms are intimately linked, and abnormal progression of each process leads to changes in the intestinal environment. Alterations in microbial communities lead to changes in functional structures based on the metabolites produced in the gut, and these environmental changes result in various bacterial infections and chronic enteric inflammatory diseases. Here, we illustrate how antibiotics are associated with an increased risk of antibiotic-associated diseases by driving intestinal environment changes that favor the proliferation and virulence of pathogens. Understanding the pathogenesis caused by antibiotics would be a crucial key to the treatment of antibiotic-associated diseases by mitigating changes in the intestinal environment and restoring it to its original state.
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Effects of the Administration of Probiotics on Fecal Microbiota Diversity and Composition in Healthy Individuals.
Noh, CK, Kim, BS, Hong, G, Cheong, JY, Lee, KJ
Journal of neurogastroenterology and motility. 2018;24(3):452-459
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Probiotics are popular health supplements taken by the general population. The influence of probiotics on the composition of gut microbiota has not been fully evaluated, and the duration of the effects of probiotics administration is still unclear. This study aimed to investigate the changes in the composition and diversity of gut microbiota by the administration of probiotics in healthy individuals. The study was carried out in Korea. 12 healthy volunteers aged between 30 and 42 years were given probiotic capsules containing five billion colony forming units of a mixture Bifidobacterium, Lactobacillus, and Enterococcus for four weeks. Stool samples were collected at the beginning of the study, after four weeks of probiotics, and again two weeks after stopping the probiotics. The overall diversity of faecal microbiota was not significantly altered by the probiotics, but significantly decreased two weeks after stopping them. The composition of faecal microbiota was not significantly changed by the probiotics at the phylum level, but the proportions of Bacteroidetes and Actinobacteria significantly changed 2 weeks after stopping the probiotics. The proportions of Lactobacillus and Enterococcus were significantly increased by the probiotics, but the proportions of Bifidobacterium, Lactobacillus, and Enterococcus decreased two weeks after stopping the probiotics. There was no difference in the levels of calprotectin between the start and end of the study. The authors concluded that the proportion of faecal microbiota at the genus level, but not diversity, is significantly altered by the administration of probiotics in healthy people. This effect does not seem to last long, probably because of homeostasis or dietary influence.
Abstract
BACKGROUND/AIMS: Probiotics are expected to modify the composition of gut microbiota. We aimed to investigate the changes in the composition and diversity of gut microbiota by the administration of probiotics in healthy individuals. METHODS Twelve healthy volunteers with age range of 30-42 years provided baseline fecal samples. Subsequently, they took commercially available probiotic capsules (a mixture for Bifidobacterium, Lactobacillus, and Enterococcus) for 4 weeks. Fecal samples were collected at 4 weeks of administration and 2 weeks after the stop of administration. Fecal microbiota was analyzed via 16S ribosomal RNA gene sequencing. RESULTS The mean Shannon index was not significantly altered by the 4-week administration of probiotics (4.365 vs 4.556, P > 0.05). The proportion of Bacteroidetes, Actinobacteria, Firmicutes , and Proteobacteria was not significantly changed by the 4-week administration of probiotics. At the genus level, the proportions of Lactobacillus (2.138% vs 2.773%, P = 0.028) and Enterococcus (0.022% vs 2.758%, P = 0.004) significantly increased 4 weeks after the administration of probiotics, but reduced 2 weeks after the stop of administration (2.773% vs 3.292%, P = 0.064 and 2.758% vs 0.001%, P = 0.001). CONCLUSIONS The diversity of fecal microbiota is not significantly affected by 4 weeks of probiotics administration. The proportion of fecal microbiota at the genus level is significantly altered by the administration of probiotics. However, this effect does not seem to last long, probably because of homeostasis or dietary influence.
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Prenatal and postnatal antibiotic exposure influences the gut microbiota of preterm infants in neonatal intensive care units.
Zou, ZH, Liu, D, Li, HD, Zhu, DP, He, Y, Hou, T, Yu, JL
Annals of clinical microbiology and antimicrobials. 2018;17(1):9
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Disturbances in gut bacteria could have long-term effects on a baby’s health. The development of healthy gut bacteria is influenced by factors such as the surrounding environment, gestational age, delivery mode, feeding method and exposure to antibiotics. The aim of this study was to investigate the effects of antibiotic exposure on the development of gut bacteria in premature babies. This study was carried out in a hospital in China. 28 premature babies who had been admitted to the neonatal intensive care unit were included in the study. Stool samples were collected when the babies were 7 and 14 days old. The researchers found that the characteristics of the gut bacteria in babies exposed to antibiotics was different to those who were not. The numbers of beneficial Bifidobacterium were significantly lower in those babies who had received antibiotics compared to those who had not. Exposure to antibiotics for more than 7 days led to increases in the presence of some strains of drug-resistant bacteria. The authors concluded that antibiotic exposure may affect the composition of early gut bacteria in premature babies which could potentially increase the risk of contracting harmful infections.
Abstract
BACKGROUND To explore the influences of prenatal antibiotic exposure, the intensity of prenatal and postnatal antibiotic exposure on gut microbiota of preterm infants and whether gut microbiota and drug resistant strains in the neonatal intensive care unit (NICU) over a defined period are related. METHODS Among 28 preterm infants, there were two groups, the PAT (prenatal antibiotic therapy) group (12 cases), and the PAF (prenatal antibiotic free) group (12 cases). Fecal samples from both groups were collected on days 7 and 14. According to the time of prenatal and postnatal antibiotic exposure, cases were divided into two groups, H (high) group (11 cases) and L (low) group (11 cases), and fecal samples on day 14 were collected. Genomic DNA was extracted from the fecal samples and was subjected to high throughput 16S rRNA amplicon sequencing. Bioinformatics methods were used to analyze the sequencing results. RESULTS Prenatal and postnatal antibiotic exposure exercised influence on the early establishment of intestinal microflora of preterm infants. Bacteroidetes decreased significantly in the PAT group (p < 0.05). The number of Bifidobacterium significantly decreased in the PAT group and H group (p < 0.05). The early gut microbiota of preterm infants with prenatal and postnatal antibiotic exposure was similar to resistant bacteria in NICU during the same period. CONCLUSION Prenatal and postnatal antibiotic exposure may affect the composition of early gut microbiota in preterm infants. Antibiotic-resistant bacteria in NICU may play a role in reshaping the early gut microbiota of preterm infants with prenatal and postnatal antibiotic exposure.
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Association between duration of intravenous antibiotic administration and early-life microbiota development in late-preterm infants.
Zwittink, RD, Renes, IB, van Lingen, RA, van Zoeren-Grobben, D, Konstanti, P, Norbruis, OF, Martin, R, Groot Jebbink, LJM, Knol, J, Belzer, C
European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology. 2018;37(3):475-483
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Premature newborn babies are commonly given antibiotics in hospital to prevent or treat infections such as sepsis. This study, carried out in the Netherlands, looked at the effect of intravenous antibiotics on the development of the gut bacteria in premature babies. Stool samples were taken from 15 premature babies who had been exposed to either no antibiotic treatment, or short (less than 3 days) or long (at least 5 days) treatment with the commonly prescribed antibiotics amoxicillin or ceftazidime. At 3 weeks old, babies who had been treated with both short and long courses of antibiotics had significantly lower abundance of the beneficial bacteria Bifidobacterium than those who had received no antibiotics. In babies who received antibiotic treatment lasting 5 days or more, Bifidobacterium levels didn’t recover until they were 6 weeks old. Antibiotics were effective against Enterobacteriaceae, but allowed Enterococcus to thrive and remain dominant for up to two weeks after antibiotic treatment was stopped. The authors concluded that intravenous antibiotics during the first week of a baby’s life greatly affects the gut bacteria. However, short courses of antibiotics allow for a quicker recovery compared to longer courses. Disturbances in the development of gut bacteria caused by antibiotic treatment could influence the development of infants' immune and digestive systems.
Abstract
Antibiotic treatment is common practice in the neonatal ward for the prevention and treatment of sepsis, which is one of the leading causes of mortality and morbidity in preterm infants. Although the effect of antibiotic treatment on microbiota development is well recognised, little attention has been paid to treatment duration. We studied the effect of short and long intravenous antibiotic administration on intestinal microbiota development in preterm infants. Faecal samples from 15 preterm infants (35 ± 1 weeks gestation and 2871 ± 260 g birth weight) exposed to no, short (≤ 3 days) or long (≥ 5 days) treatment with amoxicillin/ceftazidime were collected during the first six postnatal weeks. Microbiota composition was determined through 16S rRNA gene sequencing and by quantitative polymerase chain reaction (qPCR). Short and long antibiotic treat ment significantly lowered the abundance of Bifidobacterium right after treatment (p = 0.027) till postnatal week three (p = 0.028). Long treatment caused Bifidobacterium abundance to remain decreased till postnatal week six (p = 0.009). Antibiotic treatment was effective against members of the Enterobacteriaceae family, but allowed Enterococcus to thrive and remain dominant for up to two weeks after antibiotic treatment discontinuation. Community richness and diversity were not affected by antibiotic treatment, but were positively associated with postnatal age (p < 0.023) and with abundance of Bifidobacterium (p = 0.003). Intravenous antibiotic administration during the first postnatal week greatly affects the infant's gastrointestinal microbiota. However, quick antibiotic treatment cessation allows for its recovery. Disturbances in microbiota development caused by short and, more extensively, by long antibiotic treatment could affect healthy development of the infant via interference with maturation of the immune system and gastrointestinal tract.
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Infectious complications following probiotic ingestion: a potentially underestimated problem? A systematic review of reports and case series.
Costa, RL, Moreira, J, Lorenzo, A, Lamas, CC
BMC complementary and alternative medicine. 2018;18(1):329
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This article is a systematic review of case reports and case series published between 1976 and 2018, evaluating serious infections in the context of probiotic intake. The authors found 67 articles, 60 case reports and 7 case series, corresponding to 93 patients. Whilst they believe that these cases represent only a small proportion of existing cases, they also point out that the proportion of cases of infectious complications is small when the total number of people who use probiotics is considered. Fungemia was the most commonly observed complication, with 37.6% of the cases, sepsis was identified in 31.2% patients; bacteraemia was responsible for 20.4% of cases, followed by endocarditis and abscess, with 4 and 3 cases, respectively. Of the fungal complications, 50.5% were due to Saccharomyces spp., Lactobacillus spp. were the etiologic agents in 26 and Bifidobacterium in 12 cases of infectious complications. Infectious complications were more likely in the elderly, children under 1 (especially premature babies), and patients with central venous access or receiving enteral or parenteral nutrition. Immunosuppressive medication was reported in 15% of patients and antibiotic use in 43%. All-cause mortality was 19.6%. The authors conclude that the use of probiotics cannot be considered risk free and should be carefully evaluated for high-risk groups of patients.
Abstract
BACKGROUND Little is studied about complications related to probiotic ingestion. This study proposes to present a synthesis and critical evaluation of the reports and series of cases on the infectious complications related to the ingestion of probiotics, which can raise awareness for the prescribing and use of probiotics for certain groups of patients. METHODS Systematic review of reports and series of cases researched in the PubMed, SciELO and Scopus databases published until August 2018. The references of the articles were investigated manually for the search of cross references. SPSS version 23.0 was used for descriptive statistics and univariate analysis. RESULTS We found 60 case reports and 7 case series, making up a total of 93 patients. Fungemia was the most common infectious complications with 35 (37.6%) cases. The genus Saccharomyces was the most frequent with 47 (50.6%) cases, followed by Lactobacillus, Bifidobacterium, Bacillus, Pedioccocus and Escherichia with 26 (27.9%), 12 (12.8%), 5 (5.4%), 2 (2.2%) and 1 (1.1%) case, respectively. Adults over 60 years of age, Clostridium difficile colitis, antibiotic use and Saccharomyces infections were associated with overall mortality. HIV infections, immunosuppressive drugs, solid organ transplantation, deep intravenous lines, enteral or parenteral nutrition were not associated with death. CONCLUSION The use of probiotics cannot be considered risk-free and should be carefully evaluated for some patient groups. TRIAL REGISTRATION CRD42016042289.
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Gut microbiome alterations in Alzheimer's disease.
Vogt, NM, Kerby, RL, Dill-McFarland, KA, Harding, SJ, Merluzzi, AP, Johnson, SC, Carlsson, CM, Asthana, S, Zetterberg, H, Blennow, K, et al
Scientific reports. 2017;7(1):13537
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Research into what causes Alzheimer’s Disease (AD) is on-going, including a proposal for a potential role of human bacterial profiles. This cross-sectional study of 25 patients diagnosed with AD and 25 individuals with no AD diagnosis (matched for age, sex, ethnicity, BMI and diabetes status) aimed to compare the gut microbiome between AD and non-AD states using faecal samples. The researchers found that the gut microbiome of the AD patients was less diverse and compositionally distinct from the age-matched control group. In particular, the AD group had decreased Firmicutes and Bifidobacterium and increased Bacteriodetes compared with control. This small study suggests therefore that the gut microbiome may be a target for therapeutic manipulation when working with patients with AD.
Abstract
Alzheimer's disease (AD) is the most common form of dementia. However, the etiopathogenesis of this devastating disease is not fully understood. Recent studies in rodents suggest that alterations in the gut microbiome may contribute to amyloid deposition, yet the microbial communities associated with AD have not been characterized in humans. Towards this end, we characterized the bacterial taxonomic composition of fecal samples from participants with and without a diagnosis of dementia due to AD. Our analyses revealed that the gut microbiome of AD participants has decreased microbial diversity and is compositionally distinct from control age- and sex-matched individuals. We identified phylum- through genus-wide differences in bacterial abundance including decreased Firmicutes, increased Bacteroidetes, and decreased Bifidobacterium in the microbiome of AD participants. Furthermore, we observed correlations between levels of differentially abundant genera and cerebrospinal fluid (CSF) biomarkers of AD. These findings add AD to the growing list of diseases associated with gut microbial alterations, as well as suggest that gut bacterial communities may be a target for therapeutic intervention.