Antibiotic use and microbiome function Ferrer, Manuel; Méndez-García, Celia; Rojo, David ...
Biochemical pharmacology,
06/2017, Volume:
134
Journal Article
Peer reviewed
Effects of antibiotics in the microbiota and its microbial products representing the microbiome function. Human microbiota is exposed to multiple antibiotics each of them affecting different ...components of the microbiome. Display omitted
Our microbiome should be understood as one of the most complex components of the human body. The use of β-lactam antibiotics is one of the microbiome covariates that influence its composition. The extent to which our microbiota changes after an antibiotic intervention depends not only on the chemical nature of the antibiotic or cocktail of antibiotics used to treat specific infections, but also on the type of administration, duration and dose, as well as the level of resistance that each microbiota develops. We have begun to appreciate that not all bacteria within our microbiota are vulnerable or reactive to different antibiotic interventions, and that their influence on both microbial composition and metabolism may differ. Antibiotics are being used worldwide on a huge scale and the prescription of antibiotics is continuing to rise; however, their effects on our microbiota have been reported for only a limited number of them. This article presents a critical review of the antibiotics or antibiotic cocktails whose use in humans has been linked to changes in the composition of our microbial communities, with a particular focus on the gut, oral, respiratory, skin and vaginal microbiota, and on their molecular agents (genes, proteins and metabolites). We review the state of the art as of June 2016, and cover a total of circa 68 different antibiotics. The data herein are the first to compile information about the bacteria, fungi, archaea and viruses most influenced by the main antibiotic treatments prescribed nowadays.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
In this paper, a detailed review on the recent advances in the production of biofuels and biochemicals from microalgae and Jatropha is presented. This review includes critical elements of the ...sustainability of microalgae and Jatropha biorefineries such as technical analysis, socioeconomic considerations, and environmental impact assessments that are reported in recent studies. The integration of microalgae and Jatropha as viable feedstock for the production of biofuels and biochemicals which may serve as sustainable alternatives to fossils fuels and petrochemicals is also modeled using SuperPro designer. A technoeconomic assessment of the integrated biorefinery is carried out. United Arab Emirates (UAE) is considered as a geographical reference for the technoeconomic assessment. Three scenarios are examined. All scenarios involve the production of biodiesel and glycerol. In addition to these two products, the production of animal feed, organic fertilizer and biogas is considered in scenario 1. In scenario 2, the biorefinery products include bioethanol, organic fertilizer and biogas. Scenario 3 involves the production of hydrogen and animal feed. Scenario 1 is the base case, with which other scenarios are compared. Scenario 1 is profitable but scenarios 2 and 3 are not profitable. In addition, emissions from scenario 2 make it less attractive when it is compared to other scenarios. The integrated biorefinery with microalgae and Jatropha as feedstock is technically feasible and economically profitable in scenario 1, as modeled.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Composition of the gut microbiota changes during ageing, but questions remain about whether age is also associated with deficits in microbiome function and whether these changes occur sharply or ...progressively. The ability to define these deficits in populations of different ages may help determine a chronological age threshold at which deficits occur and subsequently identify innovative dietary strategies for active and healthy ageing. Here, active gut microbiota and associated metabolic functions were evaluated using shotgun proteomics in three well‐defined age groups consisting of 30 healthy volunteers, namely, ten infants, ten adults and ten elderly individuals. Samples from each volunteer at intervals of up to 6 months (n = 83 samples) were used for validation. Ageing gradually increases the diversity of gut bacteria that actively synthesize proteins, that is by 1.4‐fold from infants to elderly individuals. An analysis of functional deficits consistently identifies a relationship between tryptophan and indole metabolism and ageing (p < 2.8e−8). Indeed, the synthesis of proteins involved in tryptophan and indole production and the faecal concentrations of these metabolites are directly correlated (r2 > .987) and progressively decrease with age (r2 > .948). An age threshold for a 50% decrease is observed ca. 11–31 years old, and a greater than 90% reduction is observed from the ages of 34–54 years. Based on recent investigations linking tryptophan with abundance of indole and other “healthy” longevity molecules and on the results from this small cohort study, dietary interventions aimed at manipulating tryptophan deficits since a relatively “young” age of 34 and, particularly, in the elderly are recommended.
An “aged” microbiota is deficient in TrpB and TnaA proteins, which lead to a decrease in the production of tryptophan and the healthspan promoter indole. Dietary interventions aimed at manipulating the deficits of indole and tryptophan in the elderly is recommended.
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DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Airborne ultrafine particles (UFP) have been related to adverse health effects, but exposure in vulnerable population groups such as children is still not well understood. We aim to review the ...scientific literature regarding personal exposure to UFP in different microenvironments in populations until 18 years of age. The bibliographical search was carried out in July 2019 using the online database PubMed and was completed with references in articles found in the search. We selected the studies that used continuous counters and measured UFP levels in both specific microenvironment (houses, schools, transport, etc) and personal exposure. Finally, 32 studies fulfilled the criteria: of these, 10 analyzed personal exposure and 22 examined UFP levels in the microenvironment (especially in schools or nurseries (18/22)) and five in various microenvironments (including dwellings and means of transport, where exposure levels were higher). The characteristics of the microenvironments with the greatest levels of UFP were being close to heavy traffic or near cooking and cleaning activities. This review revealed the wide differences in exposure assessment methodologies that could lead to a lack of uniform and comparable information about the real UFP exposure in children.
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DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Nitrogen metabolism in gut systems remains poorly studied in spite of its importance for microbial growth and its implications for the metabolism of the host. Prevotella spp. are the most predominant ...bacteria detected in the rumen, but their presence has also been related to health and disease states in the human gut and oral cavity. To explore the metabolic networks for nitrogen assimilation in this bacterium, changes in gene expression profiles in response to variations in the available nitrogen source and to different concentrations of ammonium were analyzed by microarray and reverse transcription quantitative PCR, and linked with function by further proteomic analysis. The observed patterns of transcript abundances for genes involved in ammonium assimilation differed from the classical "enteric paradigm" for nitrogen utilization. Expression of genes encoding high substrate affinity nitrogen assimilation enzymes (GS-GOGAT system) was similar in growth-limiting and non-limiting nitrogen concentrations in P. ruminicola 23, whereas E. coli and Salmonella spp. responses to excess nitrogen involve only low substrate affinity enzymes. This versatile behavior might be a key feature for ecological success in habitats such as the rumen and human colon where nitrogen is rarely limiting for growth, and might be linked to previously reported Prevotella spp. population imbalances relative to other bacterial species in gut systems.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Acid mine drainage (AMD) emplacements are low-complexity natural systems. Low-pH conditions appear to be the main factor underlying the limited diversity of the microbial populations thriving in ...these environments, although temperature, ionic composition, total organic carbon, and dissolved oxygen are also considered to significantly influence their microbial life. This natural reduction in diversity driven by extreme conditions was reflected in several studies on the microbial populations inhabiting the various micro-environments present in such ecosystems. Early studies based on the physiology of the autochthonous microbiota and the growing success of omics-based methodologies have enabled a better understanding of microbial ecology and function in low-pH mine outflows; however, complementary omics-derived data should be included to completely describe their microbial ecology. Furthermore, recent updates on the distribution of eukaryotes and archaea recovered through sterile filtering (herein referred to as filterable fraction) in these environments demand their inclusion in the microbial characterization of AMD systems. In this review, we present a complete overview of the bacterial, archaeal (including filterable fraction), and eukaryotic diversity in these ecosystems, and include a thorough depiction of the metabolism and element cycling in AMD habitats. We also review different metabolic network structures at the organismal level, which is necessary to disentangle the role of each member of the AMD communities described thus far.
Abstract
Our microbiota presents peculiarities and characteristics that may be altered by multiple factors. The degree and consequences of these alterations depend on the nature, strength and ...duration of the perturbations as well as the structure and stability of each microbiota. The aim of this review is to sketch a very broad picture of the factors commonly influencing different body sites, and which have been associated with alterations in the human microbiota in terms of composition and function. To do so, first, a graphical representation of bacterial, fungal and archaeal genera reveals possible associations among genera affected by different factors. Then, the revision of sequence-based predictions provides associations with functions that become part of the active metabolism. Finally, examination of microbial metabolite contents and fluxes reveals whether metabolic alterations are a reflection of the differences observed at the level of population structure, and in the last step, link microorganisms to functions under perturbations that differ in nature and aetiology. The utilisation of complementary technologies and methods, with a special focus on metabolomics research, is thoroughly discussed to obtain a global picture of microbiota composition and microbiome function and to convey the urgent need for the standardisation of protocols.
The authors provide new insights into the association between multiple factors and alterations in our microbiota; data revision, technical challenges and methods, particularly metabolomics, are thoroughly discussed within the context of linking microorganisms to genes and proteins, and subsequently to functions.
The aim is to describe our experience with Cefiderocol as a rescue treatment for critical care patients with severe infections due to multi-resistant GNB.
Observational, retrospective study. We ...included every patient admitted to the department of Critical Care Medicine who received treatment with Cefiderocol. We collected demographical data, ICU length of stay, APACHE-II score, reason for being admitted, and the need of invasive mechanical ventilation or continuous renal replacement therapy. We defined clinical success as a combination of survival, improvement of signs and symptoms of infection and absence of recurrent infection due to the same bacterial species >7 days after finishing treatment with Cefiderocol. Our standard dose of cefiderocol was a prolonged infusion (3 h) of 2 g of Cefiderocol diluted in 100 cc of saline solution.
We have treated a total of 8 patients with cefiderocol. All of them were males (100%), with a median age of 63.5 years (IQR 58–68.5) Median APACHE-II was 22.5 (IQR 15.5–25). The cause of admission was bilateral pneumonia due to SARS-CoV2 in two of them (25%), septic shock in one of them (12.5%), pneumonia in one of them (12.5%), cardiac arrest in 3 of them (37.5%), and complication post-surgery in one of them (12.5%). Most of them experienced a prolonged stay in intensive care describe by a mean of days between admission and isolation of the multi-resistant bacteria of 36.25 (+/− 19.17). The standard duration of treatment was 14 days. In one patient the treatment continued after hospital discharge due to the finding of endocarditis. Clinical success was accomplished in 5 (62.5%) patients. All of these 5 patients were successfully discharged from ICU and eventually from hospital with the exception of one due to limitation of life support therapies because of brain damage detected by cerebral MRI. Reasons for not achieving clinical success: continuous isolation of the pathogen despite improvement of signs and symptoms, transfer to his country and reatment for 2 days before switching to other antibiotic following sensibilities.
WE have limited experience with Cefiderocol. It has been used in difficult patients, with a prolonged length of stay and several risk factors. In patients who were able to complete 14 days of treatment, clinical success was achieved in all of them, and microbiological success only failed in one of them.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract
Motivation
Identifying peptides associated with the major histocompability complex class II (MHCII) is a central task in the evaluation of the immunoregulatory function of therapeutics and ...drug prototypes. MHCII-peptide presentation prediction has multiple biopharmaceutical applications, including the safety assessment of biologics and engineered derivatives in silico, or the fast progression of antigen-specific immunomodulatory drug discovery programs in immune disease and cancer. This has resulted in the collection of large-scale datasets on adaptive immune receptor antigenic responses and MHC-associated peptide proteomics. In parallel, recent deep learning algorithmic advances in protein language modeling have shown potential in leveraging large collections of sequence data and improve MHC presentation prediction.
Results
Here, we train a compact transformer model (AEGIS) on human and mouse MHCII immunopeptidome data, including a preclinical murine model, and evaluate its performance on the peptide presentation prediction task. We show that the transformer performs on par with existing deep learning algorithms and that combining datasets from multiple organisms increases model performance. We trained variants of the model with and without MHCII information. In both alternatives, the inclusion of peptides presented by the I-Ag7 MHC class II molecule expressed by nonobese diabetic mice enabled for the first time the accurate in silico prediction of presented peptides in a preclinical type 1 diabetes model organism, which has promising therapeutic applications.
Availability and implementation
The source code is available at https://github.com/Novartis/AEGIS.
Acid mine drainages are characterized by their low pH and the presence of dissolved toxic metallic species. Microorganisms survive in different microhabitats within the ecosystem, namely water, ...sediments, and biofilms. In this report, we surveyed the microbial diversity within all domains of life in the different microhabitats at Los Rueldos abandoned mercury underground mine (NW Spain), and predicted bacterial function based on community composition. Sediment samples contained higher proportions of soil bacteria (AD3, Acidobacteria), as well as Crenarchaeota and Methanomassiliicoccaceae archaea. Oxic and hypoxic biofilm samples were enriched in bacterial iron oxidizers from the genus
, order Acidithiobacillales, class Betaproteobacteria, and archaea from the class Thermoplasmata. Water samples were enriched in Cyanobacteria and Thermoplasmata archaea at a 3-98% of the sunlight influence, whilst Betaproteobacteria, Thermoplasmata archaea, and Micrarchaea dominated in acid water collected in total darkness. Stalactites hanging from the Fe-rich mine ceiling were dominated by the neutrophilic iron oxidizer
and other lineages that were absent in the rest of the microhabitats (e.g., Chlorobi, Chloroflexi). Eukaryotes were detected in biofilms and open-air water samples, and belonged mainly to clades SAR (Alveolata and Stramenopiles), and Opisthokonta (Fungi). Oxic and hypoxic biofilms displayed higher proportions of ciliates (
), whereas water samples were enriched in fungi (
and unknown microbial Helotiales). Predicted function through bacterial community composition suggested adaptive evolutive convergence of function in heterogeneous communities. Our study showcases a broad description of the microbial diversity across different microhabitats in the same environment and expands the knowledge on the diversity of microbial eukaryotes in AMD habitats.
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