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2.
J Nutr ; 154(5): 1582-1587, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38521191

RESUMO

BACKGROUND: Iron deficiency is the most common nutritional deficiency worldwide, particularly for young children and females of reproductive age. Although oral iron supplements are routinely recommended and generally considered safe, iron supplementation has been shown to alter the fecal microbiota in low-income countries. Little is known about the effect of iron supplementation on the fecal microbiota in high-income settings. OBJECTIVES: To assess the effect of oral iron supplementation compared with placebo on the gut microbiome in nonpregnant females of reproductive age in a high-income country. METHODS: A 21-d prospective parallel design double-blind, randomized control trial conducted in South Australia, Australia. Females (18-45 y) were randomly assigned to either iron (65.7 mg ferrous fumarate) or placebo. Fecal samples were collected prior to commencing supplements and after 21 d of supplementation. The primary outcome was microbiota ß-diversity (paired-sample weighted unique fraction metric dissimilarity) between treatment and placebo groups after 21 d of supplementation. Exploratory outcomes included changes in the relative abundance of bacterial taxa. RESULTS: Of 82 females randomly assigned, 80 completed the trial. There was no significant difference between the groups for weighted unique fraction metric dissimilarity (mean difference: 0.003; 95% confidence interval: -0.007, 0.014; P = 0.52) or relative abundance of common bacterial taxa or Escherichia-Shigella (q > 0.05). CONCLUSIONS: Iron supplementation did not affect the microbiome of nonpregnant females of reproductive age in Australia. This trial was registered at clinicaltrials.gov as NCT05033483.


Assuntos
Suplementos Nutricionais , Fezes , Microbioma Gastrointestinal , Humanos , Feminino , Microbioma Gastrointestinal/efeitos dos fármacos , Adulto , Método Duplo-Cego , Adulto Jovem , Fezes/microbiologia , Adolescente , Ferro/administração & dosagem , Ferro/farmacologia , Pessoa de Meia-Idade , Austrália do Sul , Anemia Ferropriva , Estudos Prospectivos
6.
BMC Geriatr ; 23(1): 521, 2023 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-37641010

RESUMO

BACKGROUND: The emergence of antimicrobial-resistant bacteria represents a considerable threat to human health, particularly for vulnerable populations such as those living in residential aged care. However, antimicrobial resistance carriage and modes of transmission remain incompletely understood. The Generating evidence on antimicrobial Resistance in the Aged Care Environment (GRACE) study was established to determine principal risk factors of antimicrobial resistance carriage and transmission in residential aged care facilities (RACFs). This article describes the cohort characteristics, national representation, and planned analyses for this study. METHODS: Between March 2019 and March 2020, 279 participants were recruited from five South Australian RACFs. The median age was 88.6 years, the median period in residence was 681 days, and 71.7% were female. A dementia diagnosis was recorded in 54.5% and more than two thirds had moderate to severe cognitive impairment (68.8%). 61% had received at least one course of antibiotics in the 12 months prior to enrolment. RESULTS: To investigate the representation of the GRACE cohort to Australians in residential aged care, its characteristics were compared to a subset of the historical cohort of the Registry of Senior Australians (ROSA). This included 142,923 individuals who were permanent residents of RACFs on June 30th, 2017. GRACE and ROSA cohorts were similar in age, sex, and duration of residential care, prevalence of health conditions, and recorded dementia diagnoses. Differences were observed in care requirements and antibiotic exposure (both higher for GRACE participants). GRACE participants had fewer hospital visits compared to the ROSA cohort, and a smaller proportion were prescribed psycholeptic medications. CONCLUSIONS: We have assembled a cohort of aged care residents that is representative of the Australian aged care population, and which provides a basis for future analyses. Metagenomic data isolated from participants and built environments will be used to determine microbiome and resistome characteristics of an individual and the facility. Individual and facility risk exposures will be aligned with metagenomic data to identify principal determinants for antimicrobial resistance carriage. Ultimately, this analysis will inform measures aimed at reducing the emergence and spread of antimicrobial resistant pathogens in this high-risk population.


Assuntos
Antibacterianos , Demência , Humanos , Feminino , Idoso , Idoso de 80 Anos ou mais , Masculino , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Austrália , Farmacorresistência Bacteriana , Fatores Etários , Demência/diagnóstico , Demência/tratamento farmacológico , Demência/epidemiologia
7.
Microbiol Spectr ; 11(4): e0083123, 2023 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-37347185

RESUMO

Long-term low-dose macrolide therapy is now widely used in the treatment of chronic respiratory diseases for its immune-modulating effects, although the antimicrobial properties of macrolides can also have collateral impacts on the gut microbiome. We investigated whether such treatment altered intestinal commensal microbiology and whether any such changes affected systemic immune and metabolic regulation. In healthy adults exposed to 4 weeks of low-dose erythromycin or azithromycin, as used clinically, we observed consistent shifts in gut microbiome composition, with a reduction in microbial capacity related to carbohydrate metabolism and short-chain fatty acid biosynthesis. These changes were accompanied by alterations in systemic biomarkers relating to immune (interleukin 5 [IL-5], IL-10, monocyte chemoattractant protein 1 [MCP-1]) and metabolic (serotonin [5-HT], C-peptide) homeostasis. Transplantation of erythromycin-exposed murine microbiota into germ-free mice demonstrated that changes in metabolic homeostasis and gastrointestinal motility, but not systemic immune regulation, resulted from changes in intestinal microbiology caused by macrolide treatment. Our findings highlight the potential for long-term low-dose macrolide therapy to influence host physiology via alteration of the gut microbiome. IMPORTANCE Long-term macrolide therapy is widely used in chronic respiratory diseases although its antibacterial activity can also affect the gut microbiota, a key regulator of host physiology. Macrolide-associated studies on the gut microbiota have been limited to short antibiotic courses and have not examined its consequences for host immune and metabolic regulation. This study revealed that long-term macrolides depleted keystone bacteria and impacted host regulation, mediated directly by macrolide activity or indirectly by alterations to the gut microbiota. Understanding these macrolide-associated mechanisms will contribute to identifying the risk of long-term exposure and highlights the importance of targeted therapy for maintenance of the gut microbiota.


Assuntos
Microbioma Gastrointestinal , Doenças Respiratórias , Animais , Camundongos , Macrolídeos/farmacologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Eritromicina/farmacologia , Doenças Respiratórias/tratamento farmacológico
8.
Int J Infect Dis ; 134: 168-171, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37343782

RESUMO

Multidrug-resistant organisms (MDROs) are a major international health threat. In many low and middle-income countries poorly regulated antibiotic use, limited surveillance, and inadequate sanitation give rise to high rates of antibiotic resistance. A resulting reliance on last-line antibiotic options further contributes to the emergence of MDROs. The potential for these pathogens to spread across international borders is a matter of considerable concern. However, this problem is commonly framed as primarily a threat to the health security of countries where resistance is not yet endemic. In fact, it is little acknowledged that those at greatest risk from antibiotic treatment failure are individuals who move from regions of high MDRO prevalence to settings where standard empirical treatment options remain largely effective. In this perspective, we highlight the poor treatment outcomes for disseminated bacterial infections in individuals who have moved from settings in which MDROs are common to those where MDROs are currently less common. We discuss MDRO screening strategies that could avoid stigmatizing vulnerable populations by focusing on future risk of disseminated infection, rather than past risk of acquisition. In practical terms, this means screening individuals before childbirth, immunosuppressive treatments, major surgery, or other events associated with disseminated infection risk, rather than prioritizing screening for individuals from regions with high carriage rates. We argue that such measures would reduce antibiotic treatment failure and improve outcomes while protecting migrant populations from the divisive consequences of targeted screening programs.


Assuntos
Infecções Bacterianas , Infecções , Migrantes , Humanos , Antibacterianos/uso terapêutico , Antibacterianos/farmacologia , Farmacorresistência Bacteriana Múltipla , Infecções/tratamento farmacológico , Infecções Bacterianas/tratamento farmacológico , Bactérias Gram-Negativas
9.
Behav Anal Pract ; 16(1): 156-171, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35401945

RESUMO

Educators continue to experience stress and burnout, both of which have been negatively impacted by the COVID-19 pandemic, and there continues to be a need to develop interventions that support not only educators' well-being, but a climate within school buildings that fosters psychological well-being for students and school staff alike. Acceptance and Commitment Therapy (ACT) is one promising approach to interventions for both educator and student psychological well-being. The present study sought to evaluate the effect of a low-dosage, online, and remotely delivered ACT intervention for educators on self-reported burnout, psychological flexibility, ACT knowledge, and frequency of use of ACT-consistent language while teaching in an alternative educational setting. The ACT-based intervention targeted the development of educator psychological flexibility, but the analysis provided an evaluation of non-targeted participants' use of ACT-consistent language in the classroom, as well. Results suggest an overall improvement in participants' self-reported burnout and psychological flexibility, an increase in participants' ACT knowledge following each phase of the study, and an increase in the frequency of ACT-consistent language for all participants following the onset of a feedback component. We discuss potential implications of practical ACT-based interventions for educators in an applied setting and related increases in ACT-consistent verbal stimuli within the classroom setting.

10.
Age Ageing ; 51(12)2022 12 05.
Artigo em Inglês | MEDLINE | ID: mdl-36580555

RESUMO

COVID-19 has demonstrated the devastating consequences of the rapid spread of an airborne virus in residential aged care. We report the use of CO2-based ventilation assessment to empirically identify potential 'super-spreader' zones within an aged care facility, and determine the efficacy of rapidly implemented, inexpensive, risk reduction measures.


Assuntos
COVID-19 , Humanos , Idoso , SARS-CoV-2 , Ventilação , Comportamento de Redução do Risco
11.
Antimicrob Agents Chemother ; 66(4): e0224621, 2022 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-35293783

RESUMO

While the use of long-term macrolide therapy to prevent exacerbations in chronic respiratory diseases is widespread, its impact on the oropharyngeal microbiota and macrolide resistance, and the potential for onward transmission of resistance to close contacts are poorly understood. We determined the effects of long-term exposure to azithromycin or erythromycin on phenotypic and genotypic macrolide resistance within the oropharyngeal microbiome of healthy adults and their close contacts in a randomized, single-blinded, parallel-group trial of 4 weeks of twice-daily oral 400 mg erythromycin ethylsuccinate or twice-daily oral 125 mg azithromycin. Using oropharyngeal swabs collected from 20 index healthy adults and 20 paired close contacts, the oropharyngeal microbial composition and macrolide resistance in streptococci were assessed by 16S rRNA sequencing and antibiotic susceptibility testing of oropharyngeal cultures, respectively, at baseline and weeks 4 and 8 (washout). Targeted quantitative PCR of antibiotic resistance genes was performed to evaluate paired changes in resistance gene levels in index patients and close contacts and to relate the potential transmission of antibiotic resistance. Neither azithromycin nor erythromycin altered oropharyngeal microbiota characteristics significantly. Proportional macrolide resistance in oropharyngeal streptococci increased with both erythromycin and azithromycin, remaining above baseline levels for the azithromycin group at washout. Levels of resistance genes increased significantly with azithromycin[erm(B) and mef] and erythromycin (mef), returning to baseline levels at washout only for the erythromycin group. We found no evidence of onward transmission of resistance to close contacts, as indicated by the lack of concomitant changes in resistance gene levels detected in close contacts. (This study has been registered with the Australian and New Zealand Clinical Trials Registry under identifier ACTRN12617000278336.).


Assuntos
Antibacterianos , Microbiota , Adulto , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Austrália , Azitromicina/farmacologia , Azitromicina/uso terapêutico , Farmacorresistência Bacteriana/genética , Eritromicina/farmacologia , Humanos , Macrolídeos/farmacologia , RNA Ribossômico 16S/genética , Streptococcus
12.
Chest ; 162(1): 56-65, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35122749

RESUMO

BACKGROUND: Long-term macrolide therapy has been shown to provide benefit to those with a range of chronic respiratory conditions. However, concerns remain about the impact of macrolide exposure on the carriage and abundance of antibiotic resistance genes within the oropharynx. The potential for onward transmission of resistance from macrolide recipients to their close contacts also is poorly understood. RESEARCH QUESTION: Does long-term macrolide use impact carriage of resistance within the oropharyngeal microbiota in people with chronic respiratory conditions and risk of onward transmission to their close contacts? STUDY DESIGN AND METHODS: Oropharyngeal swabs were collected from 93 individuals with chronic respiratory conditions, 53 of whom were receiving long-term macrolide therapy. An oropharyngeal swab also was collected from a close cohabiting contact of each patient. Detection and abundance of 10 macrolide-associated resistance genes with the potential to disseminate via horizontal gene transfer were assessed by quantitative polymerase chain reaction analysis. RESULTS: Detection of resistance genes in macrolide recipients was comparable with that in nonrecipients. However, the normalized gene abundance of erm(B) was significantly higher in the macrolide recipient group (P = .045). Among the close contacts, no between-group differences in resistance gene detection or abundance were identified. Within-group analysis showed that the detection of erm(F) and mef in macrolide recipients, but not nonrecipients, was associated significantly with detection in close contacts (P = .003 and P = .004, respectively). However, between-group analysis showed that treatment group did not predict cocarriage between patients and their close contacts (P > .05 for each gene). INTERPRETATION: Although levels of erm(B) were higher in those receiving long-term macrolide therapy and evidence of gene cocarriage with close contacts was found, no evidence was found that macrolide use increased the onward transmission risk to their close contacts. This study therefore addresses concerns that long-term macrolide therapy could promote the dissemination of transmissible macrolide resistance.


Assuntos
Antibacterianos , Macrolídeos , Farmacorresistência Bacteriana/genética , Humanos , Macrolídeos/farmacologia , Macrolídeos/uso terapêutico , Orofaringe
13.
BMC Microbiol ; 22(1): 24, 2022 01 13.
Artigo em Inglês | MEDLINE | ID: mdl-35026986

RESUMO

BACKGROUND: Otitis media (OM) is a major disease burden in Australian Aboriginal children, contributing to serious long-term health outcomes. We report a pilot analysis of OM in children attending an outreach ear and hearing clinic in a remote south Australian community over a two-year period. Our study focuses on longitudinal relationships between ear canal microbiota characteristics with nasopharyngeal microbiota, and clinical and treatment variables. RESULTS: Middle ear health status were assessed in 19 children (aged 3 months to 8 years) presenting in remote western South Australia and medical interventions were recorded. Over the two-year study period, chronic suppurative OM was diagnosed at least once in 7 children (37%), acute OM with perforation in 4 children (21%), OM with effusion in 11 children (58%), while only 1 child had no ear disease. Microbiota analysis of 19 children (51 sets of left and right ear canal swabs and nasopharyngeal swabs) revealed a core group of bacterial taxa that included Corynebacterium, Alloiococcus, Staphylococcus, Haemophilus, Turicella, Streptococcus, and Pseudomonas. Within-subject microbiota similarity (between ears) was significantly greater than inter-subject similarity, regardless of differences in ear disease (p = 0.0006). Longitudinal analysis revealed changes in diagnosis to be associated with more pronounced changes in microbiota characteristics, irrespective of time interval. Ear microbiota characteristics differed significantly according to diagnosis (P (perm) = 0.0001). Diagnoses featuring inflammation with tympanic membrane perforation clustering separately to those in which the tympanic membrane was intact, and characterised by increased Proteobacteria, particularly Haemophilus influenzae, Moraxella catarrhalis, and Oligella. While nasopharyngeal microbiota differed significantly in composition to ear microbiota (P (perm) = 0.0001), inter-site similarity was significantly greater in subjects with perforated tympanic membranes, a relationship that was associated with the relative abundance of H. influenzae in ear samples (rs = - 0.71, p = 0.0003). Longitudinal changes in ear microbiology reflected changes in clinical signs and treatment. CONCLUSIONS: Children attending the ear and hearing clinic in a remote Aboriginal community present with a broad spectrum of OM conditions and severities, consistent with other remote Aboriginal communities. Ear microbiota characteristics align with OM diagnosis and change with disease course. Nasopharyngeal microbiota characteristics are consistent with the contribution of acute upper respiratory infection to OM aetiology.


Assuntos
Bactérias/isolamento & purificação , Orelha Média/microbiologia , Orelha Média/patologia , Microbiota , Havaiano Nativo ou Outro Ilhéu do Pacífico/estatística & dados numéricos , Otite Média/microbiologia , Austrália/epidemiologia , Bactérias/classificação , Bactérias/genética , Bactérias/patogenicidade , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Estudos Longitudinais , Masculino , Nasofaringe/microbiologia , Otite Média/epidemiologia , Projetos Piloto , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/microbiologia , População Rural/estatística & dados numéricos
14.
Eur Respir J ; 59(5)2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-34588194

RESUMO

BACKGROUND: Chronic airway inflammation is the main driver of pathogenesis in respiratory diseases such as severe asthma, chronic obstructive pulmonary disease, cystic fibrosis (CF) and bronchiectasis. While the role of common pathogens in airway inflammation is widely recognised, the influence of other microbiota members is still poorly understood. METHODS: We hypothesised that the lung microbiota contains bacteria with immunomodulatory activity which modulate net levels of immune activation by key respiratory pathogens. Therefore, we assessed the immunomodulatory effect of several members of the lung microbiota frequently reported as present in CF lower respiratory tract samples. RESULTS: We show that Rothia mucilaginosa, a common resident of the oral cavity that is also often detectable in the lower airways in chronic disease, has an inhibitory effect on pathogen- or lipopolysaccharide-induced pro-inflammatory responses, in vitro (three-dimensional cell culture model) and in vivo (mouse model). Furthermore, in a cohort of adults with bronchiectasis, the abundance of Rothia species was negatively correlated with pro-inflammatory markers (interleukin (IL)-8 and IL-1ß) and matrix metalloproteinase (MMP)-1, MMP-8 and MMP-9 in sputum. Mechanistic studies revealed that R. mucilaginosa inhibits NF-κB pathway activation by reducing the phosphorylation of IκBα and consequently the expression of NF-κB target genes. CONCLUSIONS: These findings indicate that the presence of R. mucilaginosa in the lower airways potentially mitigates inflammation, which could in turn influence the severity and progression of chronic respiratory disorders.


Assuntos
Bronquiectasia , Fibrose Cística , Animais , Anti-Inflamatórios/farmacologia , Bactérias , Bronquiectasia/microbiologia , Humanos , Inflamação , Pulmão , Camundongos , NF-kappa B , Escarro/microbiologia
15.
J Infect ; 83(6): 637-643, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34606783

RESUMO

BACKGROUND: Infection control is critical to safe hospital care. However, how bacteria within nosocomial environments relate to space utilisation and occupancy remains poorly understood. Our aim was to characterise the hospital microbiome in the context of the closure of a tertiary hospital and the opening of a new facility. METHODS: Environmental swabs were collected from common and inpatient areas in the old and new hospitals during a 12-month transition period. Microbiota characteristics were determined by 16S rRNA gene sequencing and quantitative (q)PCR. Targeted assays were used to detect Methicillin-resistant Staphylococcus aureus (MRSA) and vanB-positive Vancomycin-Resistant Enterococci (VRE). RESULTS: The transition to full occupancy in the new facility was associated with an increase in bacterial load (inpatient areas, 3 months p = 0.001; common areas, 6 months p = 0.039) and a change in microbiota composition (baseline-12 months, PERMANOVA p = 0.002). These changes were characterised by an increase in human microbiota-associated taxa, including Acinetobacter and Veillonella. Closure of the existing facility was associated with a decrease in bacterial load (p = 0.040). Detection of MRSA did not differ significantly between sites. CONCLUSIONS: Occupancy is a major determinant of bacterial dispersion within hospital environments. Steady-state bacterial levels and microbiota composition provide a basis for assessment of infection control measures.


Assuntos
Infecção Hospitalar , Infecções por Bactérias Gram-Positivas , Staphylococcus aureus Resistente à Meticilina , Microbiota , Infecções Estafilocócicas , Hospitais , Humanos , Staphylococcus aureus Resistente à Meticilina/genética , RNA Ribossômico 16S/genética
16.
BMC Infect Dis ; 21(1): 967, 2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34535091

RESUMO

BACKGROUND: SARS-CoV-2 poses a considerable threat to those living in residential aged care facilities (RACF). RACF COVID-19 outbreaks have been characterised by the rapid spread of infection and high rates of severe disease and associated mortality. Despite a growing body of evidence supporting airborne transmission of SARS-CoV-2, current infection control measures in RACF including hand hygiene, social distancing, and sterilisation of surfaces, focus on contact and droplet transmission. Germicidal ultraviolet (GUV) light has been used widely to prevent airborne pathogen transmission. Our aim is to investigate the efficacy of GUV technology in reducing the risk of SARS-CoV-2 infection in RACF. METHODS: A multicentre, two-arm double-crossover, randomised controlled trial will be conducted to determine the efficacy of GUV devices to reduce respiratory viral transmission in RACF, as an adjunct to existing infection control measures. The study will be conducted in partnership with three aged care providers in metropolitan and regional South Australia. RACF will be separated into paired within-site zones, then randomised to intervention order (GUV or control). The initial 6-week period will be followed by a 2-week washout before crossover to the second 6-week period. After accounting for estimated within-zone and within-facility correlations of infection, and baseline infection rates (10 per 100 person-days), a sample size of n = 8 zones (n = 40 residents/zone) will provide 89% power to detect a 50% reduction in symptomatic infection rate. The primary outcome will be the incidence rate ratio of combined symptomatic respiratory infections for intervention versus control. Secondary outcomes include incidence rates of hospitalisation for complications associated with respiratory infection; respiratory virus detection in facility air and fomite samples; rates of laboratory confirmed respiratory illnesses and genomic characteristics. DISCUSSION: Measures that can be deployed rapidly into RACF, that avoid the requirement for changes in resident and staff behaviour, and that are effective in reducing the risk of airborne SARS-CoV-2 transmission, would provide considerable benefit in safeguarding a highly vulnerable population. In addition, such measures might substantially reduce rates of other respiratory viruses, which contribute considerably to resident morbidity and mortality. Trial registration Australian and New Zealand Clinical Trials Registry ACTRN12621000567820 (registered on 14th May, 2021).


Assuntos
COVID-19 , SARS-CoV-2 , Idoso , Austrália , Humanos , Estudos Multicêntricos como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento , Raios Ultravioleta
17.
Clin Exp Allergy ; 51(9): 1144-1156, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34197676

RESUMO

BACKGROUND: A high fruit and vegetable (F&V) diet reduces asthma exacerbations in adults; this has not been examined in children to date. OBJECTIVE: To investigate the effect of a 6-month, high F&V diet on the time to first asthma exacerbation in children with asthma, in a parallel-group, randomized, controlled trial. METHODS: Children (aged 3-11 years) with asthma, history of exacerbations and usual low F&V intake (≤3 serves/day) were randomized to the intervention (high F&V diet) or control group (usual diet) for 6 months. The primary outcome was time to first exacerbation requiring medical intervention. Secondary outcomes included exacerbation rate, lung function, plasma TNF-α, CRP, and IL-6, faecal microbiota and peripheral blood mononuclear cell (PBMC) histone deacetylase (HDAC) activity and G-protein coupled receptor (GPR) 41/43 and HDAC (1-11) expression. RESULTS: 67 children were randomized between September 2015 and July 2018. F&V intake (difference in change (∆): 3.5 serves/day, 95% CI: [2.6, 4.4] p < 0.001) and plasma total carotenoids (∆: 0.44 µg/ml [0.19, 0.70] p = 0.001) increased after 6 months (intervention vs control). Time to first exacerbation (HR: 0.81, 95% CI: [0.38, 1.69], p = 0.569; control vs. intervention) and exacerbation rate (IRR: 0.84, [0.47, 1.49], p = 0.553; control vs. intervention) were similar between groups. In per-protocol analysis, airway reactance z-scores increased in the intervention versus control group (X5 ∆: 0.76 [0.04, 1.48] p = 0.038, X20 ∆: 0.93 [0.23, 1.64] p = 0.009) and changes in faecal microbiota were observed though there was no difference between groups in systemic inflammation or molecular mechanisms. In the control group, CRP and HDAC enzyme activity increased, while GPR41 expression decreased. No adverse events attributable to the interventions were observed. CONCLUSION & CLINICAL RELEVANCE: A high F&V diet did not affect asthma exacerbations over the 6-month intervention, though warrants further investigation as a strategy for improving lung function and protecting against systemic inflammation in children with asthma.


Assuntos
Asma/imunologia , Asma/fisiopatologia , Dieta/métodos , Frutas , Verduras , Criança , Pré-Escolar , Feminino , Humanos , Masculino
18.
Paediatr Respir Rev ; 40: 15-23, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34140238

RESUMO

Host-microbiome interactions exert a profound influence on human physiology and health outcomes. In particular, certain characteristics of commensal microbiota during a critical period in early life are essential for the establishment of immune tone and metabolic control. An increasing body of evidence suggests that early life exposures that disrupt these interactions can substantially influence life-long risks for respiratory disease. Here, we explore how such early life exposures, including antibiotic exposure, maternal diet, preterm birth, mode of delivery, breastfeeding, and environmental variables shape the infant microbiome, and the mechanisms by such changes can in turn impact respiratory health.


Assuntos
Microbiota , Nascimento Prematuro , Antibacterianos/uso terapêutico , Aleitamento Materno , Dieta , Feminino , Humanos , Lactente , Recém-Nascido , Gravidez
19.
BMC Cancer ; 21(1): 591, 2021 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-34022842

RESUMO

BACKGROUND: The gut microbiota influences many aspects of host physiology, including immune regulation, and is predictive of outcomes in cancer patients. However, whether conventional myelosuppressive chemotherapy affects the gut microbiota in humans with non-haematological malignancy, independent of antibiotic exposure, is unknown. METHODS: Faecal samples from 19 participants with non-haematological malignancy, who were receiving conventional chemotherapy regimens but not antibiotics, were examined prior to chemotherapy, 7-12 days after chemotherapy, and at the end of the first cycle of treatment. Gut microbiota diversity and composition was determined by 16S rRNA gene amplicon sequencing. RESULTS: Compared to pre-chemotherapy samples, samples collected 7-12 days following chemotherapy exhibited increased richness (mean 120 observed species ± SD 38 vs 134 ± 40; p = 0.007) and diversity (Shannon diversity: mean 6.4 ± 0.43 vs 6.6 ± 0.41; p = 0.02). Composition was significantly altered, with a significant decrease in the relative abundance of gram-positive bacteria in the phylum Firmicutes (pre-chemotherapy median relative abundance [IQR] 0.78 [0.11] vs 0.75 [0.11]; p = 0.003), and an increase in the relative abundance of gram-negative bacteria (Bacteroidetes: median [IQR] 0.16 [0.13] vs 0.21 [0.13]; p = 0.01 and Proteobacteria: 0.015 [0.018] vs 0.03 [0.03]; p = 0.02). Differences in microbiota characteristics from baseline were no longer significant at the end of the chemotherapy cycle. CONCLUSIONS: Conventional chemotherapy results in significant changes in gut microbiota characteristics during the period of predicted myelosuppression post-chemotherapy. Further study is indicated to link microbiome changes during chemotherapy to clinical outcomes.


Assuntos
Antineoplásicos/efeitos adversos , Microbioma Gastrointestinal/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , Medula Óssea/efeitos dos fármacos , DNA Bacteriano/isolamento & purificação , Fezes/microbiologia , Feminino , Microbioma Gastrointestinal/genética , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos , RNA Ribossômico 16S/genética
20.
Antimicrob Resist Infect Control ; 10(1): 56, 2021 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-33736699

RESUMO

BACKGROUND: Antimicrobial resistance (AMR) represents a profound global health threat. Reducing AMR spread requires the identification of transmission pathways. The extent to which hospital wards represent a venue for substantial AMR transmission in low- and middle-income countries settings is poorly understood. METHODS: Rectal swabs were obtained from adult male inpatients in a "Nightingale" model general medicine ward in Yangon, Myanmar. Resistome characteristics were characterised by metagenomic sequencing. AMR gene carriage was related to inter-patient distance (representing inter-patient interaction) using distance-based linear models. Clinical predictors of AMR patterns were identified through univariate and multivariate regression. RESULTS: Resistome similarity showed a weak but significant positive correlation with inter-patient distance (r = 0.12, p = 0.04). Nineteen AMR determinants contributed significantly to this relationship, including those encoding ß-lactamase activity (OXA-1, NDM-7; adjusted p < 0.003), trimethoprim resistance (dfrA14, adjusted p = 0.0495), and chloramphenicol resistance (catB3, adjusted p = 0.002). Clinical traits of co-located patients carrying specific AMR genes were not random. Specifically, AMR genes that contributed to distance-resistome relationships (OXA-1, catB3, dfrA14) mapped to tuberculosis patients, who were placed together according to ward policy. In contrast, patients with sepsis were not placed together, and carried AMR genes that were not spatially significant or consistent with shared antibiotic exposure. CONCLUSIONS: AMR dispersion patterns primarily reflect the placement of particular patients by their condition, rather than AMR transmission. The proportion of AMR determinants that varied with inter-patient distance was limited, suggesting that nosocomial transmission is a relatively minor contributor to population-level carriage.


Assuntos
Farmacorresistência Bacteriana Múltipla/genética , Metagenômica , Análise Espacial , Adolescente , Adulto , Idoso , Antibacterianos/farmacologia , Estudos Transversais , Países em Desenvolvimento , Hospitais , Hospitais Públicos , Hospitais de Ensino , Humanos , Controle de Infecções , Pacientes Internados , Masculino , Pessoa de Meia-Idade , Mianmar , Quartos de Pacientes , Sepse/microbiologia , Centros de Atenção Terciária , Tuberculose/microbiologia , Adulto Jovem
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