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Article ; Online: Increased habitual flavonoid intake predicts attenuation of cognitive ageing in twins

Amy Jennings / Claire J. Steves / Alexander Macgregor / Tim Spector / Aedín Cassidy

BMC Medicine, Vol 19, Iss 1, Pp 1-

2021 Volume 12

Abstract: Abstract Background Although the pathophysiology of cognitive decline is multifactorial, and modifiable by lifestyle, the evidence for the role of diet on cognitive function is still accumulating, particularly the potentially preventive role of ... ...

Abstract	Abstract Background Although the pathophysiology of cognitive decline is multifactorial, and modifiable by lifestyle, the evidence for the role of diet on cognitive function is still accumulating, particularly the potentially preventive role of constituents of plant-based foods. Methods We aimed to determine whether higher habitual intake of dietary flavonoids, key components of plant-based diets, were associated with improved cognition and medial temporal lobe volumes using three complementary approaches (longitudinal, cross-sectional and co-twin analyses). In 1126 female twins (n=224 with a 10-year follow-up of diet and cognition data) aged 18–89 years, habitual intakes of total flavonoids and seven subclasses (flavanones, anthocyanins, flavan-3-ols, flavonols, flavones, polymeric flavonoids (and proanthocyanidins separately)) were calculated using validated food frequency questionnaires. Cognition was assessed using the Cambridge Neuropsychological Test Automated Battery test. Hippocampal volumes were measured in a subset using magnetic resonance imaging (16 monozygotic-twin pairs). Statistical models were adjusted for a range of diet and lifestyle factors. Results Higher intakes of flavanones (tertile (T)3-T1=0.45, 95%CI 0.13,0.77; p=0.01) and anthocyanins (T3-T1=0.45, 95%CI 0.08,0.81; p=0.02) were associated with improvements in age-related cognition score over 10 years. In cross-sectional analysis higher intake of flavanones (T3-T1= 0.12, 95% CI 0.02, 0.21; p=0.02) and proanthocyanidins (T3-T1= 0.13, 95% CI 0.02, 0.24; p=0.02) were associated with improved paired-associates learning. Higher intake of anthocyanins was significantly associated with improved executive function (T3-T1= −0.52, 95% CI 0.19, 0.84; p=0.001) and with faster simple reaction times (T3-T1= −18.1, 95% CI −35.4, −0.7; p=0.04). In co-twin analysis, those with higher anthocyanin (2.0%, p=0.01) and proanthocyanidin (2.0%, p=0.02) intakes at baseline had the largest left hippocampal volumes after 12 years. Conclusion Small increases in habitual intake of flavonoid-rich foods (containing anthocyanins, flavanones and proanthocyanidins; equivalent to approximately two servings of oranges and blueberries per day) over long time periods have the potential to attenuate cognitive ageing.
Keywords	Diet ; Flavonoids ; Cognitive ageing ; Brain volume ; Medicine ; R
Subject code	150
Language	English
Publishing date	2021-08-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Brain-age is associated with progression to dementia in memory clinic patients

Francesca Biondo / Amelia Jewell / Megan Pritchard / Dag Aarsland / Claire J. Steves / Christoph Mueller / James H. Cole

NeuroImage: Clinical, Vol 36, Iss , Pp 103175- (2022)

2022

Abstract: Background: Biomarkers for the early detection of dementia risk hold promise for better disease monitoring and targeted interventions. However, most biomarker studies, particularly in neuroimaging, have analysed artificially ‘clean’ research groups, free ...

Abstract	Background: Biomarkers for the early detection of dementia risk hold promise for better disease monitoring and targeted interventions. However, most biomarker studies, particularly in neuroimaging, have analysed artificially ‘clean’ research groups, free from comorbidities, erroneous referrals, contraindications and from a narrow sociodemographic pool. Such biases mean that neuroimaging samples are often unrepresentative of the target population for dementia risk (e.g., people referred to a memory clinic), limiting the generalisation of these studies to real-world clinical settings. To facilitate better translation from research to the clinic, datasets that are more representative of dementia patient groups are warranted. Methods: We analysed T1-weighted MRI scans from a real-world setting of patients referred to UK memory clinic services (n = 1140; 60.2 % female and mean [SD] age of 70.0[10.8] years) to derive ‘brain-age’. Brain-age is an index of age-related brain health based on quantitative analysis of structural neuroimaging, largely reflecting brain atrophy. Brain-predicted age difference (brain-PAD) was calculated as brain-age minus chronological age. We determined which patients went on to develop dementia between three months and 7.8 years after neuroimaging assessment (n = 476) using linkage to electronic health records. Results: Survival analysis, using Cox regression, indicated a 3 % increased risk of dementia per brain-PAD year (hazard ratio [95 % CI] = 1.03 [1.02,1.04], p < 0.0001), adjusted for baseline age, age2, sex, Mini Mental State Examination (MMSE) score and normalised brain volume. In sensitivity analyses, brain-PAD remained significant when time-to-dementia was at least 3 years (hazard ratio [95 % CI] = 1.06 [1.02, 1.09], p = 0.0006), or when baseline MMSE score ≥ 27 (hazard ratio [95 % CI] = 1.03 [1.01, 1.05], p = 0.0006). Conclusions: Memory clinic patients with older‐appearing brains are more likely to receive a subsequent dementia diagnosis. Potentially, brain-age could aid ...
Keywords	Brain-age ; Machine learning ; Dementia ; Ageing ; Electronic health records ; Ecological validity ; Computer applications to medicine. Medical informatics ; R858-859.7 ; Neurology. Diseases of the nervous system ; RC346-429
Subject code	616
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Diversity of symptom phenotypes in SARS-CoV-2 community infections observed in multiple large datasets

Martyn Fyles / Karina-Doris Vihta / Carole H Sudre / Harry Long / Rajenki Das / Caroline Jay / Tom Wingfield / Fergus Cumming / William Green / Pantelis Hadjipantelis / Joni Kirk / Claire J Steves / Sebastien Ourselin / Graham F Medley / Elizabeth Fearon / Thomas House

Scientific Reports, Vol 13, Iss 1, Pp 1-

2023 Volume 19

Abstract: Abstract Variability in case severity and in the range of symptoms experienced has been apparent from the earliest months of the COVID-19 pandemic. From a clinical perspective, symptom variability might indicate various routes/mechanisms by which ... ...

Abstract	Abstract Variability in case severity and in the range of symptoms experienced has been apparent from the earliest months of the COVID-19 pandemic. From a clinical perspective, symptom variability might indicate various routes/mechanisms by which infection leads to disease, with different routes requiring potentially different treatment approaches. For public health and control of transmission, symptoms in community cases were the prompt upon which action such as PCR testing and isolation was taken. However, interpreting symptoms presents challenges, for instance, in balancing the sensitivity and specificity of individual symptoms with the need to maximise case finding, whilst managing demand for limited resources such as testing. For both clinical and transmission control reasons, we require an approach that allows for the possibility of distinct symptom phenotypes, rather than assuming variability along a single dimension. Here we address this problem by bringing together four large and diverse datasets deriving from routine testing, a population-representative household survey and participatory smartphone surveillance in the United Kingdom. Through the use of cutting-edge unsupervised classification techniques from statistics and machine learning, we characterise symptom phenotypes among symptomatic SARS-CoV-2 PCR-positive community cases. We first analyse each dataset in isolation and across age bands, before using methods that allow us to compare multiple datasets. While we observe separation due to the total number of symptoms experienced by cases, we also see a separation of symptoms into gastrointestinal, respiratory and other types, and different symptom co-occurrence patterns at the extremes of age. In this way, we are able to demonstrate the deep structure of symptoms of COVID-19 without usual biases due to study design. This is expected to have implications for the identification and management of community SARS-CoV-2 cases and could be further applied to symptom-based management of other diseases ...
Keywords	Medicine ; R ; Science ; Q
Subject code	310
Language	English
Publishing date	2023-12-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Influential factors of saliva microbiota composition

Philippa M. Wells / Daniel D. Sprockett / Ruth C. E. Bowyer / Yuko Kurushima / David A. Relman / Frances M. K. Williams / Claire J. Steves

Scientific Reports, Vol 12, Iss 1, Pp 1-

2022 Volume 11

Abstract: Abstract The oral microbiota is emerging as an influential factor of host physiology and disease state. Factors influencing oral microbiota composition have not been well characterised. In particular, there is a lack of population-based studies. We ... ...

Abstract	Abstract The oral microbiota is emerging as an influential factor of host physiology and disease state. Factors influencing oral microbiota composition have not been well characterised. In particular, there is a lack of population-based studies. We undertook a large hypothesis-free study of the saliva microbiota, considering potential influential factors of host health (frailty; diet; periodontal disease), demographics (age; sex; BMI) and sample processing (storage time), in a sample (n = 679) of the TwinsUK cohort of adult twins. Alpha and beta diversity of the saliva microbiota was associated most strongly with frailty (alpha diversity: β = −0.16, Q = 0.003, Observed; β = −0.16, Q = 0.002, Shannon; β = −0.16, Q = 0.003, Simpson; Beta diversity: Q = 0.002, Bray Curtis dissimilarity) and age (alpha diversity: β = 0.15, Q = 0.006, Shannon; β = 0.12, Q = 0.003, Simpson; beta diversity: Q = 0.002, Bray Curtis dissimilarity; Q = 0.032, Weighted UniFrac) in multivariate models including age, frailty, sex, BMI, frailty and diet, and adjustment for multiple testing. Those with a more advanced age were more likely to be dissimilar in the saliva microbiota composition than younger participants (P = 5.125e−06, ANOVA). In subsample analyses, including consideration of periodontal disease (total n = 138, periodontal disease n = 66), the association with frailty remained for alpha diversity (Q = 0.002, Observed ASVs; Q = 0.04 Shannon Index), but not beta diversity, whilst age was not demonstrated to associate with alpha or beta diversity in this subsample, potentially due to insufficient statistical power. Length of time that samples were stored prior to sequencing was associated with beta diversity (Q = 0.002, Bray Curtis dissimilarity). Six bacterial taxa were associated with age after adjustment for frailty and diet. Of the factors studied, frailty and age emerged as the most influential with regards to saliva microbiota composition. Whilst age and frailty are correlates, the associations were independent of each other, ...
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2022-11-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Lifestyle mediates the role of nutrient-sensing pathways in cognitive aging

Chiara de Lucia / Tytus Murphy / Claire J. Steves / Richard J. B. Dobson / Petroula Proitsi / Sandrine Thuret

Communications Biology, Vol 3, Iss 1, Pp 1-

cellular and epidemiological evidence

2020 Volume 17

Abstract: Chiara de Lucia et al. investigate the relationships between genetic variants of nutrient-sensing gene candidates and their association with lifestyle factors and cognitive performance in a human cohort and the expression levels of those genes in in ... ...

Abstract	Chiara de Lucia et al. investigate the relationships between genetic variants of nutrient-sensing gene candidates and their association with lifestyle factors and cognitive performance in a human cohort and the expression levels of those genes in in vitro model systems. They find that ABTB1 and GRB10 are key genes involved in aging, lifestyle, and cognitive performance.
Keywords	Biology (General) ; QH301-705.5
Language	English
Publishing date	2020-04-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Impacts of dietary exposure to pesticides on faecal microbiome metabolism in adult twins

Robin Mesnage / Ruth C. E. Bowyer / Souleiman El Balkhi / Franck Saint-Marcoux / Arnaud Gardere / Quinten Raymond Ducarmon / Anoecim Robecca Geelen / Romy Daniëlle Zwittink / Dimitris Tsoukalas / Evangelia Sarandi / Efstathia I. Paramera / Timothy Spector / Claire J. Steves / Michael N. Antoniou

Environmental Health, Vol 21, Iss 1, Pp 1-

2022 Volume 14

Abstract: Abstract Background Dietary habits have a profound influence on the metabolic activity of gut microorganisms and their influence on health. Concerns have been raised as to whether the consumption of foodstuffs contaminated with pesticides can contribute ... ...

Abstract	Abstract Background Dietary habits have a profound influence on the metabolic activity of gut microorganisms and their influence on health. Concerns have been raised as to whether the consumption of foodstuffs contaminated with pesticides can contribute to the development of chronic disease by affecting the gut microbiome. We performed the first pesticide biomonitoring survey of the British population, and subsequently used the results to perform the first pesticide association study on gut microbiome composition and function from the TwinsUK registry. Methods Dietary exposure of 186 common insecticide, herbicide, or fungicide residues and the faecal microbiome in 65 twin pairs in the UK was investigated. We evaluated if dietary habits, geographic location, or the rural/urban environment, are associated with the excretion of pesticide residues. The composition and metabolic activity of faecal microbiota was evaluated using shotgun metagenomics and metabolomics respectively. We performed a targeted urine metabolomics analysis in order to evaluate whether pesticide urinary excretion was also associated with physiological changes. Results Pyrethroid and/or organophosphorus insecticide residues were found in all urine samples, while the herbicide glyphosate was found in 53% of individuals. Food frequency questionnaires showed that residues from organophosphates were higher with increased consumption of fruit and vegetables. A total of 34 associations between pesticide residue concentrations and faecal metabolite concentrations were detected. Glyphosate excretion was positively associated with an overall increased bacterial species richness, as well as to fatty acid metabolites and phosphate levels. The insecticide metabolite Br2CA, reflecting deltamethrin exposure, was positively associated with the phytoestrogens enterodiol and enterolactone, and negatively associated with some N-methyl amino acids. Urine metabolomics performed on a subset of samples did not reveal associations with the excretion of pesticide ...
Keywords	Pesticides ; Biomonitoring ; Gut microbiota ; Dietary habits ; Food intake ; Industrial medicine. Industrial hygiene ; RC963-969 ; Public aspects of medicine ; RA1-1270
Subject code	910
Language	English
Publishing date	2022-05-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Metabolomic and gut microbiome profiles across the spectrum of community-based COVID and non-COVID disease

Scientific Reports, Vol 13, Iss 1, Pp 1-

2023 Volume 15

Abstract: Abstract Whilst most individuals with SARS-CoV-2 infection have relatively mild disease, managed in the community, it was noted early in the pandemic that individuals with cardiovascular risk factors were more likely to experience severe acute disease, ... ...

Abstract	Abstract Whilst most individuals with SARS-CoV-2 infection have relatively mild disease, managed in the community, it was noted early in the pandemic that individuals with cardiovascular risk factors were more likely to experience severe acute disease, requiring hospitalisation. As the pandemic has progressed, increasing concern has also developed over long symptom duration in many individuals after SARS-CoV-2 infection, including among the majority who are managed acutely in the community. Risk factors for long symptom duration, including biological variables, are still poorly defined. Here, we examine post-illness metabolomic profiles, using nuclear magnetic resonance (Nightingale Health Oyj), and gut-microbiome profiles, using shotgun metagenomic sequencing (Illumina Inc), in 2561 community-dwelling participants with SARS-CoV-2. Illness duration ranged from asymptomatic (n = 307) to Post-COVID Syndrome (n = 180), and included participants with prolonged non-COVID-19 illnesses (n = 287). We also assess a pre-established metabolomic biomarker score, previously associated with hospitalisation for both acute pneumonia and severe acute COVID-19 illness, for its association with illness duration. We found an atherogenic-dyslipidaemic metabolic profile, including biomarkers such as fatty acids and cholesterol, was associated with longer duration of illness, both in individuals with and without SARS-CoV-2 infection. Greater values of a pre-existing metabolomic biomarker score also associated with longer duration of illness, regardless of SARS-CoV-2 infection. We found no association between illness duration and gut microbiome profiles in convalescence. This highlights the potential role of cardiometabolic dysfunction in relation to the experience of long duration symptoms after symptoms of acute infection, both COVID-19 as well as other illnesses.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2023-06-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: A heritability-based comparison of methods used to cluster 16S rRNA gene sequences into operational taxonomic units

Matthew A. Jackson / Jordana T. Bell / Tim D. Spector / Claire J. Steves

PeerJ, Vol 4, p e

2016 Volume 2341

Abstract: A variety of methods are available to collapse 16S rRNA gene sequencing reads to the operational taxonomic units (OTUs) used in microbiome analyses. A number of studies have aimed to compare the quality of the resulting OTUs. However, in the absence of a ...

Abstract	A variety of methods are available to collapse 16S rRNA gene sequencing reads to the operational taxonomic units (OTUs) used in microbiome analyses. A number of studies have aimed to compare the quality of the resulting OTUs. However, in the absence of a standard method to define and enumerate the different taxa within a microbial community, existing comparisons have been unable to compare the ability of clustering methods to generate units that accurately represent functional taxonomic segregation. We have previously demonstrated heritability of the microbiome and we propose this as a measure of each methods’ ability to generate OTUs representing biologically relevant units. Our approach assumes that OTUs that best represent the functional units interacting with the hosts’ properties will produce the highest heritability estimates. Using 1,750 unselected individuals from the TwinsUK cohort, we compared 11 approaches to OTU clustering in heritability analyses. We find that de novo clustering methods produce more heritable OTUs than reference based approaches, with VSEARCH and SUMACLUST performing well. We also show that differences resulting from each clustering method are minimal once reads are collapsed by taxonomic assignment, although sample diversity estimates are clearly influenced by OTU clustering approach. These results should help the selection of sequence clustering methods in future microbiome studies, particularly for studies of human host-microbiome interactions.
Keywords	Ecology ; Microbiology ; Computational biology ; Medicine ; R ; Biology (General) ; QH301-705.5
Subject code	310
Language	English
Publishing date	2016-08-01T00:00:00Z
Publisher	PeerJ Inc.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Use of dietary indices to control for diet in human gut microbiota studies

Ruth C. E. Bowyer / Matthew A. Jackson / Tess Pallister / Jane Skinner / Tim D. Spector / Ailsa A. Welch / Claire J. Steves

Microbiome, Vol 6, Iss 1, Pp 1-

2018 Volume 11

Abstract: Abstract Background Environmental factors have a large influence on the composition of the human gut microbiota. One of the most influential and well-studied is host diet. To assess and interpret the impact of non-dietary factors on the gut microbiota, ... ...

Abstract	Abstract Background Environmental factors have a large influence on the composition of the human gut microbiota. One of the most influential and well-studied is host diet. To assess and interpret the impact of non-dietary factors on the gut microbiota, we endeavoured to determine the most appropriate method to summarise community variation attributable to dietary effects. Dietary habits are multidimensional with internal correlations. This complexity can be simplified by using dietary indices that quantify dietary variance in a single measure and offer a means of controlling for diet in microbiota studies. However, to date, the applicability of different dietary indices to gut microbiota studies has not been assessed. Here, we use food frequency questionnaire (FFQ) data from members of the TwinsUK cohort to create three different dietary measures applicable in western-diet populations: The Healthy Eating Index (HEI), the Mediterranean Diet Score (MDS) and the Healthy Food Diversity index (HFD-Index). We validate and compare these three indices to determine which best summarises dietary influences on gut microbiota composition. Results All three indices were independently validated using established measures of health, and all were significantly associated with microbiota measures; the HEI had the highest t values in models of alpha diversity measures, and had the highest number of associations with microbial taxa. Beta diversity analyses showed the HEI explained the greatest variance of microbiota composition. In paired tests between twins discordant for dietary index score, the HEI was associated with the greatest variation of taxa and twin dissimilarity. Conclusions We find that the HEI explains the most variance in, and has the strongest association with, gut microbiota composition in a western (UK) population, suggesting that it may be the best summary measure to capture gut microbiota variance attributable to habitual diet in comparable populations.
Keywords	Microbiome ; Microbiota ; Dietary Index ; Dietary covariate ; Human microbiota ; Food frequency questionnaire ; Microbial ecology ; QR100-130
Subject code	910
Language	English
Publishing date	2018-04-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Detecting SARS-CoV-2 at point of care

Marc F. Österdahl / Karla A. Lee / Mary Ni Lochlainn / Stuart Wilson / Sam Douthwaite / Rachel Horsfall / Alyce Sheedy / Simon D. Goldenberg / Christopher J. Stanley / Tim D. Spector / Claire J. Steves

BMC Infectious Diseases, Vol 20, Iss 1, Pp 1-

preliminary data comparing loop-mediated isothermal amplification (LAMP) to polymerase chain reaction (PCR)

2020 Volume 8

Abstract: Abstract Background A cost effective and efficient diagnostic tool for COVID-19 as near to the point of care (PoC) as possible would be a game changer in the current pandemic. We tested reverse transcription loop mediated isothermal amplification (RT- ... ...

Abstract	Abstract Background A cost effective and efficient diagnostic tool for COVID-19 as near to the point of care (PoC) as possible would be a game changer in the current pandemic. We tested reverse transcription loop mediated isothermal amplification (RT-LAMP), a method which can produce results in under 30 min, alongside standard methods in a real-life clinical setting. Methods This prospective service improvement project piloted an RT-LAMP method on nasal and pharyngeal swabs on 21 residents of a high dependency care home, with two index COVID-19 cases, and compared it to multiplex tandem reverse transcription polymerase chain reaction (RT-PCR). We recorded vital signs of patients to correlate clinical and laboratory information and calculated the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of a single swab using RT-LAMP compared with the current standard, RT-PCR, as per Standards for Reporting Diagnostic Accuracy Studies (STARD) guidelines. Results The novel method accurately detected 8/10 RT-PCR positive cases and identified a further 3 positive cases. Eight further cases were negative using both methods. Using repeated RT-PCR as a “gold standard”, the sensitivity and specificity of a single novel test were 80 and 73% respectively. PPV was 73% and NPV was 83%. Incorporating retesting of low signal RT-LAMP positives improved the specificity to 100%. We also speculate that hypothermia may be a significant early clinical sign of COVID-19. Conclusions RT-LAMP testing for SARS-CoV-2 was found to be promising, fast and to work equivalently to RT-PCR methods. RT-LAMP has the potential to transform COVID-19 detection, bringing rapid and accurate testing to the PoC. RT-LAMP could be deployed in mobile community testing units, care homes and hospitals to detect disease early and prevent spread.
Keywords	Infectious and parasitic diseases ; RC109-216 ; covid19
Subject code	610
Language	English
Publishing date	2020-10-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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