scholarly journals Quantifying the impact of treatment history on plasmid-mediated resistance evolution in human gut microbiota

2019 ◽  
Vol 116 (46) ◽  
pp. 23106-23116 ◽  
Author(s):  
Burcu Tepekule ◽  
Pia Abel zur Wiesch ◽  
Roger D. Kouyos ◽  
Sebastian Bonhoeffer
Keyword(s):  
Antibiotic Resistance ◽  
Gut Microbiota ◽  
Drug Exposure ◽  
Center Of Mass ◽  
Antibiotic Use ◽  
Resistance Evolution ◽  
Treatment History ◽  
Resistant Infection ◽  
The Impact

To understand how antibiotic use affects the risk of a resistant infection, we present a computational model of the population dynamics of gut microbiota including antibiotic resistance-conferring plasmids. We then describe how this model is parameterized based on published microbiota data. Finally, we investigate how treatment history affects the prevalence of resistance among opportunistic enterobacterial pathogens. We simulate treatment histories and identify which properties of prior antibiotic exposure are most influential in determining the prevalence of resistance. We find that resistance prevalence can be predicted by 3 properties, namely the total days of drug exposure, the duration of the drug-free period after last treatment, and the center of mass of the treatment pattern. Overall this work provides a framework for capturing the role of the microbiome in the selection of antibiotic resistance and highlights the role of treatment history for the prevalence of resistance.

scholarly journals Competition and diversity determine vaccine impact on antibiotic resistance evolution

2019 ◽  
Author(s):  
Nicholas G. Davies ◽  
Stefan Flasche ◽  
Mark Jit ◽  
Katherine E. Atkins
Keyword(s):  
Antibiotic Resistance ◽  
Pneumococcal Vaccination ◽  
Antibiotic Use ◽  
Relative Strength ◽  
Antibiotic Resistant ◽  
Resistance Evolution ◽  
Pneumococcal Carriage ◽  
Bacterial Transmission ◽  
Vaccine Impact ◽  
The Impact

Bacterial vaccines can protect recipients from contracting potentially antibiotic-resistant infections. But by altering the selective balance between sensitive and resistant strains, vaccines may also help suppress—or spread—antibiotic resistance among unvaccinated individuals. Predicting the outcome requires knowing the drivers of resistance evolution. Using mathematical modelling, we identify competition and diversity as key mediators of resistance evolution. Specifically, we show that the frequency of penicillin resistance in Streptococcus pneumoniae (pneumococcus) across 27 European countries can be explained by between-host diversity in antibiotic use, heritable diversity in pneumococcal carriage duration, or within-host competition. We use our calibrated model to predict the impact of universal pneumococcal vaccination upon the prevalence of carriage, incidence of disease, and frequency of resistance for S. pneumoniae. The relative strength and directionality of competition between resistant and sensitive pneumococcal strains determines whether vaccination promotes, inhibits, or has little effect on the evolution of antibiotic resistance. Finally, we find that differences in overall bacterial transmission and carriage alter predictions, suggesting that evidence-based policies for managing resistance with vaccines must be tailored to both pathogen and setting.One sentence summaryCompetition and diversity are key to antibiotic resistance evolution and determine whether vaccines will prevent or increase resistant infections.

scholarly journals From Intrauterine to Extrauterine Life—The Role of Endogenous and Exogenous Factors in the Regulation of the Intestinal Microbiota Community and Gut Maturation in Early Life

2021 ◽  
Vol 8 ◽  
Author(s):  
Anna Socha-Banasiak ◽  
Malwina Pawłowska ◽  
Elżbieta Czkwianianc ◽  
Kateryna Pierzynowska
Keyword(s):  
Immune System ◽  
Gut Microbiota ◽  
Human Life ◽  
Antibiotic Use ◽  
Lymphoid Cells ◽  
Microbial Colonization ◽  
Digestive Tube ◽  
The Impact ◽  
Gut Maturation

Differentiation of the digestive tube and formation of the gut unit as a whole, are regulated by environmental factors through epigenetic modifications which enhance cellular plasticity. The critical period of DNA imprinting lasts from conception until approximately the 1,000th day of human life. During pregnancy, besides agents that may directly promote epigenetic programming (e.g., folate, zinc, and choline supplementation), some factors (e.g., antibiotic use, dietary components) can affect the composition of the mother's microbiota, in turn affecting the fetal microbiome which interacts with the offspring's intestinal epithelial cells. According to available literature that confirms intrauterine microbial colonization, the impact of the microbiome and its metabolites on the genome seems to be key in fetal development, including functional gut maturation and the general health status of the offspring, as well as later on in life. Although the origin of the fetal microbiome is still not well-understood, the bacteria may originate from both the vagina, as the baby is born, as well as from the maternal oral cavity/gut, through the bloodstream. Moreover, the composition of the fetal gut microbiota varies depending on gestational age, which in turn possibly affects the regulation of the immune system at the barrier between mother and fetus, leading to differences in the ability of microorganisms to access and survive in the fetal environment. One of the most important local functions of the gut microbiota during the prenatal period is their exposure to foreign antigens which in turn contributes to immune system and tissue development, including fetal intestinal Innate Lymphoid Cells (ILCs). Additional factors that determine further infant microbiome development include whether the infant is born premature or at term, the method of delivery, maternal antibiotic use, and the composition of the mother's milk, among others. However, the latest findings highlight the fact that a more diverse infant gut microbiome at birth facilitates the proliferation of stem cells by microbial metabolites and accelerates infant development. This phenomenon confirms the unique role of microbiome. This review emphasizes the crucial perinatal and postnatal factors that may influence fetal and neonatal microbiota, and in turn gut maturation.

scholarly journals Insights into the Impact of Microbiota in the Treatment of NAFLD/NASH and Its Potential as a Biomarker for Prognosis and Diagnosis

Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 145
Author(s):  
Julio Plaza-Díaz ◽  
Patricio Solis-Urra ◽  
Jerónimo Aragón-Vela ◽  
Fernando Rodríguez-Rodríguez ◽  
Jorge Olivares-Arancibia ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Fecal Microbiota Transplantation ◽  
Liver Steatosis ◽  
Intestinal Barrier ◽  
Fecal Microbiota ◽  
Current Treatment ◽  
Immune Defense ◽  
Alcoholic Fatty Liver ◽  
The Impact

Non-alcoholic fatty liver disease (NAFLD) is an increasing cause of chronic liver illness associated with obesity and metabolic disorders, such as hypertension, dyslipidemia, or type 2 diabetes mellitus. A more severe type of NAFLD, non-alcoholic steatohepatitis (NASH), is considered an ongoing global health threat and dramatically increases the risks of cirrhosis, liver failure, and hepatocellular carcinoma. Several reports have demonstrated that liver steatosis is associated with the elevation of certain clinical and biochemical markers but with low predictive potential. In addition, current imaging methods are inaccurate and inadequate for quantification of liver steatosis and do not distinguish clearly between the microvesicular and the macrovesicular types. On the other hand, an unhealthy status usually presents an altered gut microbiota, associated with the loss of its functions. Indeed, NAFLD pathophysiology has been linked to lower microbial diversity and a weakened intestinal barrier, exposing the host to bacterial components and stimulating pathways of immune defense and inflammation via toll-like receptor signaling. Moreover, this activation of inflammation in hepatocytes induces progression from simple steatosis to NASH. In the present review, we aim to: (a) summarize studies on both human and animals addressed to determine the impact of alterations in gut microbiota in NASH; (b) evaluate the potential role of such alterations as biomarkers for prognosis and diagnosis of this disorder; and (c) discuss the involvement of microbiota in the current treatment for NAFLD/NASH (i.e., bariatric surgery, physical exercise and lifestyle, diet, probiotics and prebiotics, and fecal microbiota transplantation).

scholarly journals The gut-microbiota-brain axis in autism: what Drosophila models can offer?

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Safa Salim ◽  
Ayesha Banu ◽  
Amira Alwa ◽  
Swetha B. M. Gowda ◽  
Farhan Mohammad
Keyword(s):  
Gut Microbiota ◽  
Gut Microbiome ◽  
Neurological Disorders ◽  
Autism Spectrum ◽  
Brain Disorders ◽  
Mediated Communication ◽  
The Impact ◽  
Insight Into ◽  
Drosophila Models

AbstractThe idea that alterations in gut-microbiome-brain axis (GUMBA)-mediated communication play a crucial role in human brain disorders like autism remains a topic of intensive research in various labs. Gastrointestinal issues are a common comorbidity in patients with autism spectrum disorder (ASD). Although gut microbiome and microbial metabolites have been implicated in the etiology of ASD, the underlying molecular mechanism remains largely unknown. In this review, we have summarized recent findings in human and animal models highlighting the role of the gut-brain axis in ASD. We have discussed genetic and neurobehavioral characteristics of Drosophila as an animal model to study the role of GUMBA in ASD. The utility of Drosophila fruit flies as an amenable genetic tool, combined with axenic and gnotobiotic approaches, and availability of transgenic flies may reveal mechanistic insight into gut-microbiota-brain interactions and the impact of its alteration on behaviors relevant to neurological disorders like ASD.

Role of the gut microbiota in airway immunity and host defense against respiratory infections

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Maike Willers ◽  
Dorothee Viemann
Keyword(s):  
Gut Microbiota ◽  
Host Defense ◽  
Gut Microbiome ◽  
Respiratory Infections ◽  
Current Knowledge ◽  
Viral Pathogens ◽  
Commensal Microbiota ◽  
Enhanced Resistance ◽  
The Impact

Abstract Colonization of the intestine with commensal bacteria is known to play a major role in the maintenance of human health. An altered gut microbiome is associated with various ensuing diseases including respiratory diseases. Here, we summarize current knowledge on the impact of the gut microbiota on airway immunity with a focus on consequences for the host defense against respiratory infections. Specific gut commensal microbiota compositions and functions are depicted that mediate protection against respiratory infections with bacterial and viral pathogens. Lastly, we highlight factors that have imprinting effects on the establishment of the gut microbiota early in life and are potentially relevant in the context of respiratory infections. Deepening our understanding of these relationships will allow to exploit the knowledge on how gut microbiome maturation needs to be modulated to ensure lifelong enhanced resistance towards respiratory infections.

scholarly journals Risk factors for respiratory Aspergillus fumigatus in German Cystic Fibrosis patients and impact on lung function

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Uta Düesberg ◽  
Julia Wosniok ◽  
Lutz Naehrlich ◽  
Patience Eschenhagen ◽  
Carsten Schwarz
Keyword(s):  
Risk Factors ◽  
Cystic Fibrosis ◽  
Lung Function ◽  
Aspergillus Fumigatus ◽  
Age Groups ◽  
Antibiotic Use ◽  
Lower Lung ◽  
Lung Infections ◽  
The Impact

Abstract Airway inflammation and chronic lung infections in cystic fibrosis (CF) patients are mostly caused by bacteria, e.g. Pseudomonas aeruginosa (PA). The role of fungi in the CF lung is still not well elucidated, but evidence for a harmful and complex role is getting stronger. The most common filamentous fungus in CF is Aspergillus fumigatus (AF). Age and continuous antibiotic treatment have been discussed as risk factors for AF colonisation but did not differentiate between transient and persistent AF colonisation. Also, the impact of co-colonisation of PA and AF on lung function is still under investigation. Data from patients with CF registered in the German Cystic Fibrosis Registry database in 2016 and 2017 were retrospectively analysed, involving descriptive and multivariate analysis to assess risk factors for transient or persistent AF colonisation. Age represented an independent risk factor for persistent AF colonisation. Prevalence was low in children less than ten years, highest in the middle age and getting lower in higher age (≥ 50 years). Continuous antibiotic lung treatment was significantly associated with AF prevalence in all age groups. CF patients with chronic PA infection had a lower lung function (FEV1%predicted), which was not influenced by an additional AF colonisation. AF colonisation without chronic PA infection, however, was significantly associated with a lower function, too. Older age up to 49 years and continuous antibiotic use were found to be the main risk factors for AF permanent colonisation. AF might be associated with decrease of lung function if not disguised by chronic PA infection.

scholarly journals Influence of microbiota on immunity and immunotherapy for gastric and esophageal cancers

2020 ◽  
Vol 8 (3) ◽  
pp. 206-214
Author(s):  
Xiaoli Zhang ◽  
Zui Pan
Keyword(s):  
Gut Microbiota ◽  
Human Health ◽  
Potential Role ◽  
Systemic Immunity ◽  
Esophageal Cancers ◽  
The Impact

Abstract Gastric and esophageal cancers are multifactorial and multistage-involved malignancy. While the impact of gut microbiota on overall human health and diseases has been well documented, the influence of gastric and esophageal microbiota on gastric and esophageal cancers remains unclear. This review will discuss the reported alteration in the composition of gastric and esophageal microbiota in normal and disease conditions, and the potential role of dysbiosis in carcinogenesis and tumorigenesis. This review will also discuss how dysbiosis stimulates local and systemic immunity, which may impact on the immunotherapy for cancer.

scholarly journals Antibiotics in hives and their effects on honey bee physiology and behavioral development

Biology Open ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. bio053884 ◽  
Author(s):  
Yarira Ortiz-Alvarado ◽  
David R. Clark ◽  
Carlos J. Vega-Melendez ◽  
Zomary Flores-Cruz ◽  
Maria G. Domingez-Bello ◽  
...  
Keyword(s):  
Honey Bee ◽  
Bacterial Infections ◽  
Fat Body ◽  
Age Of Onset ◽  
Antibiotic Use ◽  
Behavioral Development ◽  
Human Interventions ◽  
And Behavior ◽  
The Impact

ABSTRACTRecurrent honeybee losses make it critical to understand the impact of human interventions, such as antibiotic use in apiculture. Antibiotics are used to prevent or treat bacterial infections in colonies. However, little is known about their effects on honeybee development. We studied the effect of two commercial beekeeping antibiotics on the bee physiology and behavior throughout development. Our results show that antibiotic treatments have an effect on amount of lipids and rate of behavioral development. Lipid amount in treated bees was higher than those not treated. Also, the timing of antibiotic treatment had distinct effects for the age of onset of behaviors, starting with cleaning, then nursing and lastly foraging. Bees treated during larva-pupa stages demonstrated an accelerated behavioral development and loss of lipids, while bees treated from larva to adulthood had a delay in behavioral development and loss of lipids. The effects were shared across the two antibiotics tested, TerramycinR (oxytetracycline) and TylanR (tylosin tartrate). These effects of antibiotic treatments suggest a role of microbiota in the interaction between the fat body and brain that is important for honeybee behavioral development.This paper has an associated First Person interview with the first author of the article.

scholarly journals The Role of Streptococcus pneumoniae in Community-Acquired Pneumonia

2020 ◽  
Vol 41 (04) ◽  
pp. 455-469 ◽  
Author(s):  
Charles Feldman ◽  
Ronald Anderson
Keyword(s):  
Antibiotic Resistance ◽  
Streptococcus Pneumoniae ◽  
Antimicrobial Agents ◽  
Bacterial Pathogen ◽  
Epidemiological Data ◽  
The United States ◽  
Invasive Infection ◽  
Geographic Variations ◽  
The Impact

AbstractWith the notable exceptions of the United States and Canada in particular, the global burden of disease in adults due to invasive infection with the dangerous respiratory, bacterial pathogen, Streptococcus pneumoniae (pneumococcus) remains. This situation prevails despite the major successes of inclusion of polysaccharide conjugate vaccines (PCVs) in many national childhood immunization programs and associated herd protection in adults, as well as the availability of effective antimicrobial agents. Accurate assessment of the geographic variations in the prevalence of invasive pneumococcal disease (IPD) has, however, been somewhat impeded by the limitations imposed on the acquisition of reliable epidemiological data due to reliance on often insensitive, laboratory-based, pathogen identification procedures. This, in turn, may result in underestimation of the true burden of IPD and represents a primary focus of this review. Other priority topics include the role of PCVs in the changing epidemiology of IPD in adults worldwide, smoking as a risk factor not only in respect of increasing susceptibility for development of IPD, but also in promoting pneumococcal antibiotic resistance. The theme of pneumococcal antibiotic resistance has been expanded to include mechanisms of resistance to commonly used classes of antibiotics, specifically β-lactams, macrolides and fluoroquinolones, and, perhaps somewhat contentiously, the impact of resistance on treatment outcome. Finally, but no less importantly, the role of persistent antigenemia as a driver of a chronic, subclinical, systemic proinflammatory/procoagulant phenotype that may underpin the long-term sequelae and premature mortality of those adults who have recovered from an episode of IPD, is considered.

scholarly journals Could the beneficial effects of dietary calcium on obesity and diabetes control be mediated by changes in intestinal microbiota and integrity?

2015 ◽  
Vol 114 (11) ◽  
pp. 1756-1765 ◽  
Author(s):  
J. M. G. Gomes ◽  
J. A. Costa ◽  
R. C. Alfenas
Keyword(s):  
Gut Microbiota ◽  
Metabolic Diseases ◽  
Beneficial Effects ◽  
Body Weight Reduction ◽  
Intestinal Integrity ◽  
Obesity And Diabetes ◽  
Supplementation Period ◽  
Inflammatory State ◽  
The Impact

AbstractEvidence from animal and human studies has associated gut microbiota, increased translocation of lipopolysaccharide (LPS) and reduced intestinal integrity (II) with the inflammatory state that occurs in obesity and type 2 diabetes mellitus (T2DM). Consumption of Ca may favour body weight reduction and glycaemic control, but its influence on II and gut microbiota is not well understood. Considering the impact of metabolic diseases on public health and the role of Ca on the pathophysiology of these diseases, this review critically discusses possible mechanisms by which high-Ca diets could affect gut microbiota and II. Published studies from 1993 to 2015 about this topic were searched and selected from Medline/PubMed, Scielo and Lilacs databases. High-Ca diets seem to favour the growth of lactobacilli, maintain II (especially in the colon), reduce translocation of LPS and regulate tight-junction gene expression. We conclude that dietary Ca might interfere with gut microbiota and II modulations and it can partly explain the effect of Ca on obesity and T2DM control. However, further research is required to define the supplementation period, the dose and the type of Ca supplement (milk or salt) required for more effective results. As Ca interacts with other components of the diet, these interactions must also be considered in future studies. We believe that more complex mechanisms involving extraintestinal disorders (hormones, cytokines and other biomarkers) also need to be studied.

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