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INTRODUCTION: The Covid-19 pandemic dramatically altered the way cancer care services were accessed and delivered, including for colorectal cancer (CRC). In the United Kingdom, patients were discouraged from presenting in primary care, many consultations took place remotely, investigative procedures and screening programmes were temporarily suspended, and fewer operations and treatments were delivered. People had to face the practical consequences of having cancer during a pandemic and navigate never before seen pathways, often alone. We examined the experience of being diagnosed and treated for CRC during the pandemic, and the implications of this on people's cancer journeys. METHODS: Semi-structured interviews were undertaken with people diagnosed with CRC during the Covid-19 pandemic (January 2020-May 2021), in the North East of England. An iterative topic guide was used during interviews, which took place remotely (telephone or Zoom), were audio recorded, pseudo-anonymised and transcribed. Initial transcripts were independently coded by two researchers, and a code 'bank' developed for application across transcripts. Development of themes and overarching analytical constructs was undertaken collaboratively by the research team. RESULTS: Interviews were conducted with 19 participants, analysed and four key themes identified: (1) The relative threats of Covid-19 and Cancer were not comparable, with cancer seen as posing a far greater risk than Covid-19; (2) Remote consultations were problematic, affecting patients' abilities to build rapport and trust with clinicians, assess nonverbal communication, and feel able to disclose, comprehend and retain information; (3) Stoma follow-up care was seen to be lacking, with long wait times for stoma reversal experienced by some; Finally, (4) Being alone during consultations negatively impacted some peoples' abilities to absorb information, and left them without the support of loved ones at an emotionally vulnerable time. However, some participants preferred being alone at certain points in their pathways, including receiving a diagnosis, and most frequently when receiving in-patient treatment. CONCLUSION: Being alone brought unexpected benefits, absolving people from undertaking emotions work for others, and instead focus on their recovery, however, remote consultations negatively impacted patients' experiences. This study highlights the complex benefits and burdens of pandemic-located cancer journeys, including how these shifted at different points across cancer pathways. PATIENT OR PUBLIC CONTRIBUTION: Lorraine Angell, a cancer survivor, has been central to this study from idea conception, contributing to: development of study focus and design; securing funding; production of patient-facing materials; development of interview topic guides; analysis and interpretation of data; and drafting of key findings and manuscripts.
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COVID-19 , Neoplasias Colorrectales , Humanos , COVID-19/epidemiología , Neoplasias Colorrectales/terapia , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/psicología , Femenino , Masculino , Persona de Mediana Edad , Anciano , Inglaterra , Entrevistas como Asunto , Investigación Cualitativa , SARS-CoV-2 , Reino Unido , PandemiasAsunto(s)
Neoplasias de la Boca , Telemedicina , Humanos , Neoplasias de la Boca/diagnóstico , OdontólogosRESUMEN
Objective: Cytosponge is a novel technology for oesophageal pathology diagnosis. Uses include diagnosis of Barrett's oesophagus and as a triage tool to prioritise upper gastrointestinal endoscopy. Patient experience is a key component of quality care. Previous work has developed endoscopy patient-reported experience measures. An appropriate tool to measure patient experience of Cytosponge is required. The aim of this work was to describe the patient experience of Cytosponge. Design/Method: Individuals aged 18 years or over, who had undergone Cytosponge from September 2020 to March 2021, were invited to participate in a semi-structured interview. Interviews were audio-recorded, transcribed verbatim and anonymised. Thematic analysis was undertaken. Themes were organised into two overarching areas relating to patient experiences and patient perceptions of the test. Results: 19 patients underwent interview (aged 37-80 years, 13 male). In terms of patient experiences of Cytosponge, five themes were identified: emotional reaction; expectations; environment and physical process; sensory experience; communication and information. All themes were present across all procedural phases, aside from sensory experience which was only present during the test. With regard to perception of the test, two major themes were identified: test novelty (encompassing patient awareness of the test and reaction to the new test) and trusting the test results. Conclusion: Patients must remain central to novel technologies such as Cytosponge. Measuring patient experience is essential to achieve that. This study demonstrates five major themes which describe the patient experience of this procedure. These have been used to adapt the Newcastle ENDOPREM for use in Cytosponge.
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INTRODUCTION: Approximately 10 300 people are diagnosed with pancreatic cancer each year in the UK. The cancer and its treatment inflict a significant physical, functional and emotional burden on patients. Research suggests that patients have many ongoing needs for support and care, but that these needs are not met by existing services. Family members often step in to fill this gap and provide support and care during and after treatment. Research in other cancers shows that this informal caregiving can place a very heavy burden on carers. However, there are few studies in the international literature that have focused on informal carers in pancreatic cancer; none have been conducted in the UK. METHODS AND ANALYSIS: Two complementary research methods will be utilised. First, a longitudinal quantitative study of 300 carers investigating, using validated questionnaires to assess the impact of caregiving (Caregiver Reaction Assessment), the unmet needs of carers (Supportive Care Needs Survey) and the quality-of-life (Short Form 12-item health survey), will be conducted. Second, qualitative interviews will be conducted with up to 30 carers to explore their experiences in more depth. Mixed-effects regression models will be applied to survey results to determine how impact, needs and quality-of-life vary over time, compare outcomes between carers of patients with operable and inoperable disease and identify social factors which affect outcomes. Interview data will undergo reflexive thematic analysis. ETHICS AND DISSEMINATION: The protocol has been approved by the Health Research Authority of the UK (Ethical approval IRAS ID 309503). Findings will be published in peer-reviewed journals and presented at national and international conferences.
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Cuidadores , Neoplasias Pancreáticas , Humanos , Cuidadores/psicología , Calidad de Vida , Proyectos de Investigación , Emociones , Neoplasias Pancreáticas/terapiaRESUMEN
Head and neck cancers (HNC) are often late stage at diagnosis; stage is a major determinant of prognosis. The urgent cancer referral pathway (two week wait; 2WW) within England's National Health Service aims to reduce time to diagnosis. We investigated factors associated with HNC route to diagnosis. Data were obtained from the English population-based cancer registry on 66,411 primary invasive HNCs (ICD C01-14 and C31-32) diagnosed 2006-2014. Multivariable logistic regression determined the likelihood of different diagnosis routes by patients' demographic and clinical characteristics. Significant socio-demographic inequalities were observed. Emergency presentations declined over time and 2WW increased. Significant socio-demographic inequalities were observed. Non-white patients, aged over 65, residing in urban areas with advanced disease, were more likely to have emergency presentations. White males aged 55 and older with an oropharynx cancer were more likely to be diagnosed via 2WW. Higher levels of deprivation were associated with both emergency and 2WW routes. Dental referral was more likely in women, with oral cancers and lower stage disease. Despite the decline over time in emergency presentation and the increased use of 2WW, socio-demographic variation is evident in routes to diagnosis. Further work exploring the reasons for these inequalities, and the consequences for patients' care and outcomes, is urgently required.
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Neoplasias de Cabeza y Cuello , Neoplasias Orofaríngeas , Masculino , Humanos , Femenino , Medicina Estatal , Neoplasias de Cabeza y Cuello/epidemiología , Derivación y Consulta , DemografíaRESUMEN
Introduction: Head and neck cancer (HNC) diagnosis and treatment can be a significant life trauma. Some HNC survivors experience post-traumatic growth (PTG), which has been linked with better health-related quality-of-life. Empirical research on PTG, and theoretical models, point to the importance of being able to purposely make sense of the traumatic experience. Intrusive rumination, by contrast, is linked to poorer outcomes. This study explored HNC survivors' experiences of rumination. Methods: Twenty HNC survivors between 9 months and 5 years post-diagnosis were recruited (11 male, 9 female, age range 46-83). They had a range of HNC sub-types and cancer treatments. Participants underwent a semi-structured interview about their cancer diagnosis and treatment. Reflexive thematic analysis identified themes and sub-themes around rumination. Results: Four themes with linked subthemes on the content and process of rumination were identified. Theme 1 was rumination and worry related to diagnosis. Here, survivors discussed how the HNC diagnosis and plans for treatment had dominated their initial thoughts. Theme 2 was processing the trauma of HNC. This theme reflected rumination on the traumatic experience of diagnosis and treatment and how the participant was reacting to it. Theme 3 was considering the impact. This theme encompassed retrospective thinking (e.g., on treatment decisions made) and comparisons between the participant now versus the early days after diagnosis. Theme 4 was continued rumination. This theme included ongoing intrusive and distressing rumination about the trauma and impact of cancer. Those who expressed ongoing rumination revisited fears (e.g., concerns about their future) or returned to negative experiences (e.g., distressing exchanges with healthcare professionals or what they perceived as poor care). Conclusion: This study uniquely describes the nature and content of rumination following HNC. Early intrusive rumination is common and may reflect perceptions of cancer as an existential threat. Over time, rumination can become more reflective and move towards deliberate meaning-making. Some HNC survivors may benefit from interventions to reduce barriers to this transition. The content of distressing and difficult to control rumination (commonly focused on ongoing fears or inability to resolve difficult experiences) helps to identify those who may benefit from more directed psychological support.
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Rural cancer inequalities are evident internationally, with rural cancer patients 5% less likely to survive than their urban counterparts. There is evidence to suggest that diagnostic delays prior to entry into secondary care may be contributing to these poorer rural cancer outcomes. This study explores the symptom appraisal and help-seeking decision-making of people experiencing symptoms of colorectal cancer in rural areas of England. Patients were randomly invited from 4 rural practices, serving diverse communities. Semi-structured interviews were undertaken with 40 people who had experienced symptoms of colorectal cancer in the preceding 8 weeks. Four key themes were identified as influential in participants' willingness and timeliness of consultation: a desire to rule out cancer (facilitator of help-seeking); stoicism and self-reliance (barrier to help-seeking); time scarcity (barrier to help-seeking); and GP/patient relationship (barrier or facilitator, depending on perceived strength of the relationship). Self-employed, and "native" rural residents most commonly reported experiencing time scarcity and poor GP/patient relationships as a barrier to (re-)consultation. Targeted, active safety-netting approaches, and increased continuity of care, may be particularly beneficial to expedite timely diagnoses and minimise cancer inequalities for rural populations.
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PURPOSE: The aim of this study was to identify the most appropriate measure of quality of life (QoL) for patients living with and beyond cancer. METHODS: One hundred eighty-two people attending cancer clinics in Central London at various stages post-treatment, completed a series of QoL measures: FACT-G, EORTC QLQ-C30 , IOCv2 (positive and negative subscales) and WEMWBS, a wellbeing measure. These measures were chosen as the commonest measures used in previous research. Correlation tests were used to assess the association between scales. Participants were also asked about pertinence and ease of completion. RESULTS: There was a significant positive correlation between the four domain scores of the two health-related QoL measures (.32 ≤ r ≤ .72, P < .001), and a significant large negative correlation between these and the negative IOCv2 subscale scores (- .39 ≤ r ≤ - .63, P < .001). There was a significant moderate positive correlation between positive IOCv2 subscale and WEMWBS scores (r = .35, P < .001). However, neither the FACT-G nor the EORTC showed any significant correlation with the positive IOCv2 subscale. Participants rated all measures similarly with regards to pertinence and ease of use. CONCLUSION: There was little to choose between FACT-G, EORTC, and the negative IOC scales, any of which may be used to measure QoL. However, the two IOCv2 subscales capture unique aspects of QoL compared to the other measures. The IOCv2 can be used to identify those cancer survivors who would benefit from interventions to improve their QoL and to target specific needs thereby providing more holistic and personalised care beyond cancer treatment.
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Supervivientes de Cáncer , Neoplasias , Humanos , Neoplasias/terapia , Calidad de Vida , Encuestas y Cuestionarios , Reino UnidoRESUMEN
PURPOSE: Clostridium difficile has been reported to occur in the gastrointestinal tract of 50% of Cystic Fibrosis (CF) subjects, however, clinical C. difficile infection (CDI) is a rare occurrence in this cohort despite the presence of toxigenic and hypervirulent ribotypes. Here, we present the first longitudinal, multicentre analysis of C. difficile prevalence among adult CF subjects. METHODOLOGY: Faecal samples were collected from adults with CF (selected based on confirmed Pseudomonas aeruginosa pulmonary colonisation) from Ireland, UK and Belgium as part of the CFMATTERS clinical research trial (grant No. 603038) and from non-CF controls. Faecal samples were collected on enrolment, at three monthly intervals, during pulmonary exacerbation and three months post exacerbation. C. difficile was isolated from faecal samples by ethanol shocking followed by culturing on cycloserine cefoxitin egg yolk agar. Isolates were characterised in terms of ribotype, toxin type and antibiotic susceptibility to antibiotics routinely used in the treatment of CDI (metronidazole and vancomycin) and those implicated in induction of CDI (ciprofloxacin and moxifloxacin). RESULTS: Prevalence of C. difficile among CF subjects in the three sites was similar ranging from 47% to 50% at baseline, while the healthy control cohort had a carriage rate of 7.1%. Including subjects who were positive for C. difficile at any time point there was a higher carriage rate of 71.4%, 66.7% and 63.2% in Ireland, UK, and Belgium, respectively. Ribotyping of 80 isolates from 45 CF persons, over multiple time points revealed 23 distinct ribotypes with two ribotypes (046 and 078) shared by all centres. The proportion of toxigenic isolates varied across the sites, ranging from 66.7% in Ireland to 52.9% in Belgium and 100% in the UK. Antibiotic susceptibility rates to vancomycin, metronidazole, ciprofloxacin and moxifloxacin was 100%, 97.5%, 1.3% and 63.8%, respectively. CONCLUSIONS: This study demonstrates the highest carriage rate of C. difficile to date in a CF cohort. Longitudinal data show that C. difficile can be a transient inhabitant of the CF gut, changing both in terms of strain and excretion rates.
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Clostridioides difficile , Infecciones por Clostridium , Fibrosis Quística , Adulto , Antibacterianos/uso terapéutico , Bélgica , Clostridioides difficile/genética , Infecciones por Clostridium/tratamiento farmacológico , Infecciones por Clostridium/epidemiología , Fibrosis Quística/complicaciones , Humanos , Irlanda/epidemiología , Pruebas de Sensibilidad Microbiana , RibotipificaciónRESUMEN
BACKGROUND: The interaction between genetic, epigenetic and environmental factors plays an important role in the aetiology of hypertension. GWAS and observational studies link the C677T polymorphism in methylenetetrahydrofolate reductase (MTHFR) with hypertension, while riboflavin, the MTHFR cofactor, has been shown to reduce blood pressure and global DNA methylation in homozygous (TT genotype) individuals. It is currently unclear whether riboflavin modulates DNA methylation of other hypertension-related genes. OBJECTIVES: To compare DNA methylation of hypertension-related genes in adults stratified by MTHFR genotype and effect of riboflavin intervention in adults with the variant MTHFR 677TT genotype. METHOD: Pyrosequencing was carried out for hypertension-related genes (ACE, AGTR1, GCK, GNA12, IGF2, MMP9 and NOS3) in blood samples from participants in previous trials (CC, n = 40; TT, n = 40). The effect of intervention with riboflavin (1.6 mg/d for16 weeks) or placebo on DNA methylation was investigated in adults with the variant MTHFR 677TT genotype (n = 80). RESULTS: Individuals with the MTHFR 677TT v CC genotype had significantly higher average DNA methylation at NOS3 (+1.66%, P = 0.044). In response to riboflavin supplementation in TT individuals, there was an increase in average DNA methylation at IGF2 (+1.09%, P = 0.019) and a decrease at ACE (-0.44%, P = 0.021) in females only. Specific CpG sites were hypomethylated in GNA12 and hypermethylated in AGTR1. CONCLUSION: This study provides the first RCT evidence that riboflavin alters DNA methylation of hypertension-related genes in adults with the MTHFR 677TT genotype, providing some insight into mechanisms linking hypertension with the genotype-specific response of BP to riboflavin.
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Hipertensión , Metilenotetrahidrofolato Reductasa (NADPH2) , Adulto , Metilación de ADN , Suplementos Dietéticos , Femenino , Genotipo , Humanos , Hipertensión/tratamiento farmacológico , Hipertensión/genética , Metilenotetrahidrofolato Reductasa (NADPH2)/genética , Riboflavina/uso terapéuticoRESUMEN
DNA methylation is important in regulating gene expression and genomic stability while aberrant DNA methylation is associated with disease. Riboflavin (FAD) is a cofactor for methylenetetrahydrofolate reductase (MTHFR), a critical enzyme in folate recycling, which generates methyl groups for homocysteine remethylation to methionine, the pre-cursor to the universal methyl donor S-adenosylmethionine (SAM). A polymorphism (C677T) in MTHFR results in decreased MTHFR activity and increased homocysteine concentration. Previous studies demonstrated that riboflavin modulates this phenotype in homozygous adults (MTHFR 677 TT genotype), however, DNA methylation was not considered. This study examined DNA methylation, globally and at key MTHFR regulatory sites, in adults stratified by MTHFR genotype and the effect of riboflavin supplementation on DNA methylation in individuals with the 677 TT genotype. Samples were accessed from participants, screened for the MTHFR C677T polymorphism, who participated in observational (n = 80) and targeted riboflavin (1.6 mg/day) RCTs (n = 80). DNA methylation at LINE-1 and key regulatory regions of the MTHFR locus were analysed by pyrosequencing in peripheral blood leukocytes. LINE-1 (+1.6%; p = 0.011) and MTHFR south shelf (+4.7%, p < 0.001) were significantly hypermethylated in individuals with the MTHFR 677 TT compared to CC genotype. Riboflavin supplementation resulted in decreased global methylation, albeit only significant at one CpG. A significant reduction in DNA methylation at the MTHFR north shore (-1.2%, p < 0.001) was also observed in TT adults following intervention with riboflavin. This provides the first RCT evidence that DNA methylation may be modulated by riboflavin in adults with the MTHFR 677 TT genotype.
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Metilación de ADN/efectos de los fármacos , Metilenotetrahidrofolato Reductasa (NADPH2)/genética , Riboflavina/farmacología , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mutación , Estudios Observacionales como Asunto , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
CONTEXT: Aberrant DNA methylation is linked to various diseases. The supply of methyl groups for methylation reactions is mediated by S-adenosylmethionine, which depends on the availability of folate and related B vitamins. OBJECTIVES: To investigate the influence of key nutrients involved in 1-carbon metabolism on DNA methylation in adults. DATA SOURCES: Systematic literature searches were conducted in the Cochrane Library, Medline, Embase, Cumulative Index to Nursing and Allied Health Literature Plus, Scopus, and Web of Science databases. Studies that met the inclusion criteria and were published in English were included. DATA EXTRACTION: The first author, study design, sample size, population characteristics, type and duration of intervention, tissue type or cells analyzed, molecular techniques, and DNA methylation outcomes. DATA SYNTHESIS: A meta-analysis of randomized, controlled trials (RCTs) was conducted to investigate the effect of 1-carbon metabolism nutrients on global DNA methylation. Functional analysis and visualization were performed using BioVenn software. RESULTS: From a total of 2620 papers screened by title, 53 studies met the inclusion criteria. Qualitative analysis indicated significant associations between 1-carbon metabolism nutrients and DNA methylation. In meta-analysis of RCTs stratified by method of laboratory analysis, supplementation with folic acid alone or in combination with vitamin B12 significantly increased global DNA methylation in studies using liquid chromatography-mass spectrometry, which had markedly lower heterogeneity (n = 3; Z = 3.31; P = 0.0009; I2 = 0%) in comparison to other methods. Functional analysis highlighted a subset of 12 differentially methylated regions that were significantly related to folate and vitamin B12 biomarkers. CONCLUSION: This study supports significant associations between 1-carbon metabolism nutrients and DNA methylation. However, standardization of DNA methylation techniques is recommended to reduce heterogeneity and facilitate comparison across studies. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration number: CRD42018091898.
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Metilación de ADN , Dieta , Ácido Fólico/administración & dosificación , Estado Nutricional , Vitamina B 12/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Ácido Fólico/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Nutrientes , Vitamina B 12/metabolismo , Complejo Vitamínico B/administración & dosificación , Adulto JovenRESUMEN
PURPOSE OF REVIEW: The number of cancer survivors is growing due to population ageing, earlier detection and more effective therapies. Routinely collected data (RCD), generally cancer registry data, has been used to investigate survivors' needs and outcomes. We reviewed uses of RCD since 2017, identifying novel findings and research directions. RECENT FINDINGS: Survival is improving internationally but continues to vary between subgroups. Longitudinal survivor surveys suggest malignancy-specific temporal patterns in unmet needs and health-related quality-of-life (HRQoL). Unmet needs are a risk factor for future depression and depression predicts poorer HRQoL in all domains. Emerging evidence suggests links between posttraumatic stress and poor HRQoL and posttraumatic growth and improved HRQoL. Evidence for a link between cancer-related financial hardship and poor HRQoL is accumulating. Surveys and linkage studies continue to show poorer work outcomes in survivors. Among survivors of childhood and young adult cancers, large linkage studies demonstrate significant risk of late effects, including hospitalization, pregnancy and labour complications, and cardiac death. SUMMARY: RCD plays a significant role in understanding survivors' needs and outcomes. New approaches which overlay different types of data - including detailed clinical and treatment data, biomarker data and nonhealth administrative data - have the potential to generate considerable new knowledge.
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Supervivientes de Cáncer/psicología , Salud Mental , Evaluación de Necesidades/organización & administración , Calidad de Vida/psicología , Recolección de Datos/métodos , Empleo/estadística & datos numéricos , Estado de Salud , Hospitalización/estadística & datos numéricos , Humanos , Sistema de Registros/estadística & datos numéricos , Factores de Riesgo , Factores Socioeconómicos , Trastornos por Estrés Postraumático/epidemiología , Factores de TiempoRESUMEN
OBJECTIVES: Over two million people in the UK are living with and beyond cancer. A third report diminished quality of life. DESIGN: A review of published systematic reviews to identify effective non-pharmacological interventions to improve the quality of life of cancer survivors. DATA SOURCES: Databases searched until May 2017 included PubMed, Cochrane Central, EMBASE, MEDLINE, Web of Science, the Cumulative Index to Nursing and Allied Health Literature, and PsycINFO. STUDY SELECTION: Published systematic reviews of randomised trials of non-pharmacological interventions for people living with and beyond cancer were included; included reviews targeted patients aged over 18. All participants had already received a cancer diagnosis. Interventions located in any healthcare setting, home or online were included. Reviews of alternative therapies or those non-English reports were excluded. Two researchers independently assessed titles, abstracts and the full text of papers, and independently extracted the data. OUTCOMES: The primary outcome of interest was any measure of global (overall) quality of life. ANALYTICAL METHODS: Quality assessment assessing methdological quality of systematic reviews (AMSTAR) and narrative synthesis, evaluating effectiveness of non-pharmacological interventions and their components. RESULTS: Of 14 430 unique titles, 21 were included in the review of reviews. There was little overlap in the primary papers across these reviews. Thirteen reviews covered mixed tumour groups, seven focused on breast cancer and one focused on prostate cancer. Face-to-face interventions were often combined with online, telephone and paper-based reading materials. Interventions included physical, psychological or behavioural, multidimensional rehabilitation and online approaches. Yoga specifically, physical exercise more generally, cognitive behavioural therapy (CBT) and mindfulness-based stress reduction (MBSR) programmes showed benefit in terms of quality of life. CONCLUSIONS: Exercise-based interventions were effective in the short (less than 3-8 months) and long term. CBT and MBSR also showed benefits, especially in the short term. The evidence for multidisciplinary, online and educational interventions was equivocal.
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Supervivientes de Cáncer , Neoplasias/rehabilitación , Calidad de Vida , Ejercicio Físico , Humanos , Atención Plena , Ensayos Clínicos Controlados Aleatorios como Asunto , Revisiones Sistemáticas como Asunto , YogaRESUMEN
The biological significance of Archaea in the human gut microbiota is largely unclear. We recently reported genomic and biochemical analyses of the Methanomassiliicoccales, a novel order of methanogenic Archaea dwelling in soil and the animal digestive tract. We now show that these Methanomassiliicoccales are present in published microbiome data sets from eight countries. They are represented by five Operational Taxonomic Units present in at least four cohorts and phylogenetically distributed into two clades. Genes for utilizing trimethylamine (TMA), a bacterial precursor to an atherosclerogenic human metabolite, were present in four of the six novel Methanomassiliicoccales genomes assembled from ELDERMET metagenomes. In addition to increased microbiota TMA production capacity in long-term residential care subjects, abundance of TMA-utilizing Methanomassiliicoccales correlated positively with bacterial gene count for TMA production and negatively with fecal TMA concentrations. The two large Methanomassiliicoccales clades have opposite correlations with host health status in the ELDERMET cohort and putative distinct genomic signatures for gut adaptation.
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Archaea/genética , Archaea/metabolismo , Microbioma Gastrointestinal , Metilaminas/metabolismo , Anciano , Anciano de 80 o más Años , Animales , Archaea/clasificación , Archaea/aislamiento & purificación , Heces/microbiología , Femenino , Tracto Gastrointestinal/microbiología , Genómica , Humanos , Masculino , Metagenoma , Metagenómica , Microbiota , FilogeniaRESUMEN
The gut microbiota interacts with the host via neuroimmune, neuroendocrine and neural pathways. These pathways are components of the brain-gut-microbiota axis and preclinical evidence suggests that the microbiota can recruit this bidirectional communication system to modulate brain development, function and behaviour. The pathophysiology of depression involves neuroimmune-neuroendocrine dysregulation. However, the extent to which changes in gut microbiota composition and function mediate the dysregulation of these pathways is unknown. Thirty four patients with major depression and 33 matched healthy controls were recruited. Cytokines, CRP, Salivary Cortisol and plasma Lipopolysaccharide binding protein were determined by ELISA. Plasma tryptophan and kynurenine were determined by HPLC. Fecal samples were collected for 16s rRNA sequencing. A Fecal Microbiota transplantation was prepared from a sub group of depressed patients and controls and transferred by oral gavage to a microbiota-deficient rat model. We demonstrate that depression is associated with decreased gut microbiota richness and diversity. Fecal microbiota transplantation from depressed patients to microbiota-depleted rats can induce behavioural and physiological features characteristic of depression in the recipient animals, including anhedonia and anxiety-like behaviours, as well as alterations in tryptophan metabolism. This suggests that the gut microbiota may play a causal role in the development of features of depression and may provide a tractable target in the treatment and prevention of this disorder.
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Depresión/microbiología , Depresión/patología , Microbioma Gastrointestinal/fisiología , Tracto Gastrointestinal/microbiología , Adulto , Anciano , Animales , Proteína C-Reactiva/metabolismo , Estudios de Casos y Controles , Corticosterona/sangre , Citocinas/sangre , Modelos Animales de Enfermedad , Heces/microbiología , Femenino , Preferencias Alimentarias/fisiología , Humanos , Hidrocortisona/metabolismo , Quinurenina/sangre , Lipopolisacáridos/sangre , Lipopolisacáridos/farmacología , Masculino , Aprendizaje por Laberinto/fisiología , Persona de Mediana Edad , ARN Ribosómico 16S/metabolismo , Ratas , Ratas Sprague-DawleyRESUMEN
Test parameter variations were evaluated for their effects on surotomycin MICs. Calcium concentration was the only variable that influenced MICs; therefore, 50 µg/ml (standard for lipopeptide testing) is recommended. Quality control ranges for Clostridium difficile (0.12 to 1 µg/ml) and Eggerthella lenta (broth, 1 to 4 µg/ml; agar, 1 to 8 µg/ml) were approved by the Clinical and Laboratory Standards Institute based on these data.
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Antibacterianos/farmacología , Clostridioides difficile/efectos de los fármacos , Lipopéptidos/farmacología , Pruebas de Sensibilidad Microbiana/métodos , Pruebas de Sensibilidad Microbiana/normas , Péptidos Cíclicos/farmacología , Humanos , Control de Calidad , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: High-throughput sequencing has enabled detailed insights into complex microbial environments, including the human gut microbiota. The accuracy of the sequencing data however, is reliant upon appropriate storage of the samples prior to DNA extraction. The aim of this study was to conduct the first MiSeq sequencing investigation into the effects of faecal storage on the microbiota, compared to fresh samples. Culture-based analysis was also completed. METHODS: Seven faecal samples were collected from healthy adults. Samples were separated into fresh (DNA extracted immediately), snap frozen on dry ice and frozen for 7 days at -80°C prior to DNA extraction or samples frozen at -80°C for 7 days before DNA extraction. Sequencing was completed on the Illumina MiSeq platform. Culturing of total aerobes, anaerobes and bifidobacteria was also completed. RESULTS: No significant differences at phylum or family levels between the treatment groups occurred. At genus level only Faecalibacterium and Leuconostoc were significantly different in the fresh samples compared to the snap frozen group (p = 0.0298; p = 0.0330 respectively). Diversity analysis indicated that samples clustered based on the individual donor, rather than by storage group. No significant differences occurred in the culture-based analysis between the fresh, snap or -80°C frozen samples. CONCLUSIONS: Using the MiSeq platform coupled with culture-based analysis, this study highlighted that limited significant changes in microbiota occur following rapid freezing of faecal samples prior to DNA extraction. Thus, rapid freezing of samples prior to DNA extraction and culturing, preserves the integrity of the microbiota.