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Microbiological and clinical effects of probiotics and antibiotics on nonsurgical treatment of chronic periodontitis: a randomized placebo- controlled trial with 9-month follow-up.
Morales, A, Gandolfo, A, Bravo, J, Carvajal, P, Silva, N, Godoy, C, Garcia-Sesnich, J, Hoare, A, Diaz, P, Gamonal, J
Journal of applied oral science : revista FOB. 2018;26:e20170075
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Chronic periodontitis is an inflammatory disease affecting the gums caused by the accumulation of dental bacterial plaque. There has been evidence that certain bacteria, like Tannerella forsythia, Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans, are related to the development of chronic perdontitis. Research has shown that probiotic species such as Lactobacillus rhamnosus inhibit the growth of bacteria that cause gum disease. This parallel-arm, randomised, double-blinded, placebo-controlled clinical trial investigated the effects of Lactobacillus rhamnosus SP1 or Azithromycin tablets as an addition to non-surgical therapy on clinical and microbiological parameters of chronic periodontitis in healthy subjects. Participants in the intervention group consumed a probiotic sachet containing Lactobacillus rhamnosus SP1 and an antibiotic placebo daily for three months, whereas the placebo group consumed azithromycin 500 mg for five days and a probiotic placebo. At 6 weeks follow-up, both the probiotic group and the antibiotic group demonstrated improvements in clinical and microbiological parameters with a reduction in cultivable microbiota such as Tannerella forsythia, Porphyromonas gingivalis, and Aggregatibacter actinomycetemcomitans. The antibiotic group reduced the number of people with chronic periodontitis more effectively than the probiotic group, but there was no significant difference between the two. To identify the most effective probiotic therapy for chronic periodontitis, more robust studies are required. The results of this study can be used by healthcare professionals to learn about the effects of probiotic therapy in patients with chronic periodontitis.
Abstract
The aim of this double-blind, placebo-controlled and parallel- arm randomized clinical trial was to evaluate the effects of Lactobacillus rhamnosus SP1-containing probiotic sachet and azithromycin tablets as an adjunct to nonsurgical therapy in clinical parameters and in presence and levels of Tannerella forsythia, Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans. Forty-seven systemically healthy volunteers with chronic periodontitis were recruited and monitored clinically and microbiologically at baseline for 3, 6 and 9 months after therapy. Subgingival plaque samples were collected from four periodontal sites with clinical attachment level ≥1 mm, probing pocket depth ≥4 mm and bleeding on probing, one site in each quadrant. Samples were cultivated and processed using the PCR technique. Patients received nonsurgical therapy including scaling and root planing (SRP) and were randomly assigned to a probiotic (n=16), antibiotic (n = 16) or placebo (n = 15) group. L. rhamnosus SP1 was taken once a day for 3 months. Azithromycin 500mg was taken once a day for 5 days. All groups showed improvements in clinical and microbiological parameters at all time points evaluated. Probiotic and antibiotic groups showed greater reductions in cultivable microbiota compared with baseline. The placebo group showed greater reduction in number of subjects with P. gingivalis compared with baseline. However, there were no significant differences between groups. The adjunctive use of L. rhamnosus SP1 sachets and azithromycin during initial therapy resulted in similar clinical and microbiological improvements compared with the placebo group.
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Crosstalk between the microbiome and epigenome: messages from bugs.
Qin, Y, Wade, PA
Journal of biochemistry. 2018;163(2):105-112
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Trillions of microbes live symbiotically in and on an individual human being, most of them inside the digestive tract and communally known as the gut microbiome. The gut microbiome plays a vital role in the individual host’s health, not only by helping digest food and harvest energy, but also by regulating immune development and influencing gene expression. Diet and factors, such as infections and the use of antibiotics, can alter the balance of the microbiome and lead to various outcomes. This paper reviewed the current understanding of the ways in which the gut microbiome is capable of altering the host’s gene expression through microbial signals, including metabolites, bile acids, inflammation and altered composition. The studies highlighted in the paper show that gut microbes communicate both with local cells in the intestines and with more distant organs, such as the liver and the cardiovascular system. Through this communication, they can regulate the expression of immune cells, cancer cells, enzymes and inflammation-related molecules. The authors concluded that these interactions, or the crosstalk between the microbes and the host, demonstrate a crucial role of the gut microbiome in the host’s response to environmental signals. However, many of the mechanisms are still unclear, so further studies are needed to explain specific microbe-derived signals, affecting host gene expression, and to deepen our understanding of how lifestyle, health status and environmental exposures, such as antibiotics, regulate the microbiome and its influence.
Abstract
Mammals exist in a complicated symbiotic relationship with their gut microbiome, which is postulated to have broad impacts on host health and disease. As omics-based technologies have matured, the potential mechanisms by which the microbiome affects host physiology are being addressed. The gut microbiome, which provides environmental cues, can modify host cell responses to stimuli through alterations in the host epigenome and, ultimately, gene expression. Increasing evidence highlights microbial generation of bioactive compounds that impact the transcriptional machinery in host cells. Here, we review current understanding of the crosstalk between gut microbiota and the host epigenome, including DNA methylation, histone modification and non-coding RNAs. These studies are providing insights into how the host responds to microbial signalling and are predicted to provide information for the application of precision medicine.
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Disruption of maternal gut microbiota during gestation alters offspring microbiota and immunity.
Nyangahu, DD, Lennard, KS, Brown, BP, Darby, MG, Wendoh, JM, Havyarimana, E, Smith, P, Butcher, J, Stintzi, A, Mulder, N, et al
Microbiome. 2018;6(1):124
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The gut microbiota is key for immune development, especially during a critical window in infancy, and it has been shown that maternal diet before, during and after pregnancy influences infant metabolism and gut microbiota. The aim of this study was to assess the effects of maternal antibiotics administration during gestation and nursing on offspring gut microbiota and immunity. Pregnant mice, dams, received oral vancomycin in drinking water 5 days prior to give birth (gestation group), 14 days after delivery (nursing group) or 5 days prior to delivery and throughout nursing (gestation plus nursing group), while control mice received no vancomycin. Adaptive immunity and gut microbiota in dams and pups were analysed at various times after delivery. This study showed that antibiotic alteration of maternal gut microbiota during both pregnancy and nursing results in changes in the adaptive immunity in offspring. The authors conclude these findings are important as they provide insight into the mechanism by which maternal exposures during pregnancy may impact infant health, therefore identifying potential targets for intervention.
Abstract
BACKGROUND Early life microbiota is an important determinant of immune and metabolic development and may have lasting consequences. The maternal gut microbiota during pregnancy or breastfeeding is important for defining infant gut microbiota. We hypothesized that maternal gut microbiota during pregnancy and breastfeeding is a critical determinant of infant immunity. To test this, pregnant BALB/c dams were fed vancomycin for 5 days prior to delivery (gestation; Mg), 14 days postpartum during nursing (Mn), or during gestation and nursing (Mgn), or no vancomycin (Mc). We analyzed adaptive immunity and gut microbiota in dams and pups at various times after delivery. RESULTS In addition to direct alterations to maternal gut microbial composition, pup gut microbiota displayed lower α-diversity and distinct community clusters according to timing of maternal vancomycin. Vancomycin was undetectable in maternal and offspring sera, therefore the observed changes in the microbiota of stomach contents (as a proxy for breastmilk) and pup gut signify an indirect mechanism through which maternal intestinal microbiota influences extra-intestinal and neonatal commensal colonization. These effects on microbiota influenced both maternal and offspring immunity. Maternal immunity was altered, as demonstrated by significantly higher levels of both total IgG and IgM in Mgn and Mn breastmilk when compared to Mc. In pups, lymphocyte numbers in the spleens of Pg and Pn were significantly increased compared to Pc. This increase in cellularity was in part attributable to elevated numbers of both CD4+ T cells and B cells, most notable Follicular B cells. CONCLUSION Our results indicate that perturbations to maternal gut microbiota dictate neonatal adaptive immunity.
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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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Postoperative changes of the microbiome: are surgical complications related to the gut flora? A systematic review.
Lederer, AK, Pisarski, P, Kousoulas, L, Fichtner-Feigl, S, Hess, C, Huber, R
BMC surgery. 2017;17(1):125
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Infections following gastrointestinal surgery are common and patients routinely receive antibiotic medications to reduce the risks involved. Recent reviews have suggested that some of these complications might be related to the patient’s gut bacteria profile. This systematic review of 10 studies, including 677 patients, aimed to identify the relationship between post-operative infections and the gut microbiome. All studies reported a post-operative change to the gut flora, with 5 studies showing a reduction in bacteria present. Surgery tended to lead to an increase in disease causing bacteria and a reduction in health giving bacteria. The rate of post-operative complications was lower in the groups treated with pre- and pro-biotics, suggesting that there might be a relationship between gut flora and infections following surgery. There remains uncertainty however, due to the shortcomings of the methodologies employed by the studies.
Abstract
BACKGROUND The purpose of this review was to identify the relationship between the gut microbiome and the development of postoperative complications like anastomotic leakage or a wound infection. Recent reviews focusing on underlying molecular biology suggested that postoperative complications might be influenced by the patients' gut flora. Therefore, a review focusing on the available clinical data is needed. METHODS In January 2017 a systematic search was carried out in Medline and WebOfScience to identify all clinical studies, which investigated postoperative complications after gastrointestinal surgery in relation to the microbiome of the gut. RESULTS Of 337 results 10 studies were included into this analysis after checking for eligibility. In total, the studies comprised 677 patients. All studies reported a postoperative change of the gut flora. In five studies the amount of bacteria decreased to different degrees after surgery, but only one study found a significant reduction. Surgical procedures tended to result in an increase of potentially pathogenic bacteria and a decrease of Lactobacilli and Bifidobacteria. The rate of infectious complications was lower in patients treated with probiotics/symbiotics compared to control groups without a clear relation to the systemic inflammatory response. The treatment with synbiotics/probiotics in addition resulted in faster recovery of bowel movement and a lower rate of postoperative diarrhea and abdominal cramping. CONCLUSIONS There might be a relationship between the gut flora and the development of postoperative complications. Due to methodological shortcomings of the included studies and uncontrolled bias/confounding factors there remains a high level of uncertainty.