1.
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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Mucosal microbiome dysbiosis in gastric carcinogenesis.
Coker, OO, Dai, Z, Nie, Y, Zhao, G, Cao, L, Nakatsu, G, Wu, WK, Wong, SH, Chen, Z, Sung, JJY, et al
Gut. 2018;67(6):1024-1032
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Gastric cancer (GC) is the 4th most common cancer and a leading cause of cancer-related deaths worldwide. Infection with Helicobacter pylori is an important risk factor for GC and other changes in gastric microbial composition are thought to play role in gastric carcinogenesis. This observational study aimed to elucidate the microbial changes that are characteristic for the different stages of gastric tumor development. The authors found significant changes in microbial composition in stomach cancer patients compared to patients with pre-cancerous mucosal changes, with an increase of some and a depletion of other bacteria, in particular an increase in oral bacteria, which is also found in other gastrointestinal cancers. They also found that interactions between the depleted and enriched bacterial species progressively increased with progressing carcinogenesis. Whilst there was no difference in the diversity of bacteria between H. pylori-positive and negative samples, more bacterial interactions were observed in H. pylori-negative samples. The authors conclude that significant gastric dysbiosis can be seen in samples of stomach cancer patients, however, they point out that from their study it is impossible to tell whether the bacteria increased in GC are “drivers” or “passengers” of gastric carcinogenesis. Their call for more research focusses on using this knowledge to develop better diagnostic biomarkers, rather than using this information for prevention or treatment of stomach cancer.
Abstract
OBJECTIVES We aimed to characterise the microbial changes associated with histological stages of gastric tumourigenesis. DESIGN We performed 16S rRNA gene analysis of gastric mucosal samples from 81 cases including superficial gastritis (SG), atrophic gastritis (AG), intestinal metaplasia (IM) and gastric cancer (GC) from Xi'an, China, to determine mucosal microbiome dysbiosis across stages of GC. We validated the results in mucosal samples of 126 cases from Inner Mongolia, China. RESULTS We observed significant mucosa microbial dysbiosis in IM and GC subjects, with significant enrichment of 21 and depletion of 10 bacterial taxa in GC compared with SG (q<0.05). Microbial network analysis showed increasing correlation strengths among them with disease progression (p<0.001). Five GC-enriched bacterial taxa whose species identifications correspond to Peptostreptococcus stomatis, Streptococcus anginosus, Parvimonas micra, Slackia exigua and Dialister pneumosintes had significant centralities in the GC ecological network (p<0.05) and classified GC from SG with an area under the receiver-operating curve (AUC) of 0.82. Moreover, stronger interactions among gastric microbes were observed in Helicobacter pylori-negative samples compared with H. pylori-positive samples in SG and IM. The fold changes of selected bacteria, and strengths of their interactions were successfully validated in the Inner Mongolian cohort, in which the five bacterial markers distinguished GC from SG with an AUC of 0.81. CONCLUSIONS In addition to microbial compositional changes, we identified differences in bacterial interactions across stages of gastric carcinogenesis. The significant enrichments and network centralities suggest potentially important roles of P. stomatis, D. pneumosintes, S. exigua, P. micra and S. anginosus in GC progression.
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Increased richness and diversity of the vaginal microbiota and spontaneous preterm birth.
Freitas, AC, Bocking, A, Hill, JE, Money, DM
Microbiome. 2018;6(1):117
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The bacterial community in the female lower genital tract plays an important role in the health of both mother and baby. Imbalances in the vaginal microbiota have been associated with negative reproductive outcomes, such as premature birth. Bacterial infection is thought to be an important contributor to the onset of premature labour. The objective of this study was to compare the vaginal microbiota of pregnant women who had premature births (<37 weeks) with those of pregnant women who delivered at term. Vaginal swabs were collected from 216 Canadian women at 11-16 weeks of gestational age. Of these, 170 pregnancies went to full term, and 46 women had premature births. The vaginal microbiota of women who experienced premature birth had higher richness and diversity and higher Mollicutes prevalence when compared to those of women who delivered at term. The results confirm previous reports of an association between Mollicutes and premature birth and suggest that a more diverse microbiome may contribute to the microbiome’s role in premature births.
Abstract
BACKGROUND The bacterial community present in the female lower genital tract plays an important role in maternal and neonatal health. Imbalances in this microbiota have been associated with negative reproductive outcomes, such as spontaneous preterm birth (sPTB), but the mechanisms underlying the association between a disturbed microbiota and sPTB remain poorly understood. An intrauterine infection ascending from the vagina is thought to be an important contributor to the onset of preterm labour. Our objective was to characterize the vaginal microbiota of pregnant women who had sPTB (n = 46) and compare to those of pregnant women who delivered at term (n = 170). Vaginal swabs were collected from women at 11-16 weeks of gestational age. Microbiota profiles were created by PCR amplification and pyrosequencing of the cpn60 universal target region. RESULTS Profiles clustered into seven community state types: I (Lactobacillus crispatus dominated), II (Lactobacillus gasseri dominated), III (Lactobacillus iners dominated), IVA (Gardnerella vaginalis subgroup B or mix of species), IVC (G. vaginalis subgroup A dominated), IVD (G. vaginalis subgroup C dominated) and V (Lactobacillus jensenii dominated). The microbiota of women who experienced preterm birth (< 37 weeks gestation) had higher richness and diversity and higher Mollicutes prevalence when compared to those of women who delivered at term. The two groups did not cluster according to CST, likely because CST assignment is driven in most cases by the dominance of one particular species, overwhelming the contributions of more rare taxa. In conclusion, we did not identify a specific microbial community structure that predicts sPTB, but differences in microbiota richness, diversity and Mollicutes prevalence were observed between groups. CONCLUSIONS Although a causal relationship remains to be determined, our results confirm previous reports of an association between Mollicutes and sPTB and further suggest that a more diverse microbiome may be important in the pathogenesis of some cases.
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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.