Imperial College London

DrKantaChechi

Faculty of MedicineNational Heart & Lung Institute

ISSF Fellow
 
 
 
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Norfolk PlaceSt Mary's Campus

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Publications

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26 results found

Puig-Castellvi F, Pacheco-Tapia R, Deslande M, Jia M, Andrikopoulos P, Chechi K, Bonnefond A, Froguel P, Dumas M-Eet al., 2023, Advances in the integration of metabolomics and metagenomics for human gut microbiome and their clinical applications, TRAC-TRENDS IN ANALYTICAL CHEMISTRY, Vol: 167, ISSN: 0165-9936

Journal article

Andrikopoulos P, Aron-Wisnewsky J, Chakaroun R, Myridakis A, Forslund S, Nielsen T, Adriouch S, Holmes B, Chilloux J, Vieira-Silva S, Falony G, Salem J-E, Andreelli F, Belda E, Kieswich J, Chechi K, Puig-Castellvi F, Chevalier M, Le Chatelier E, Olanipekun M, Hoyles L, Alves R, Helft G, Isnard R, Køber L, Coelho LP, Rouault C, Gauguier D, Gøtze JP, Prifti E, Froguel P, The MetaCardis C, Zucker J-D, Bäckhed F, Vestergaard H, Hansen T, Oppert J-M, Blüher M, Nielsen J, Raes J, Bork P, Yaqoob M, Stumvoll M, Pedersen O, Ehrlich SD, Clément K, Dumas M-Eet al., 2023, Evidence of a causal and modifiable relationship between kidney function and circulating trimethylamine N-oxide, Nature Communications, Vol: 14, Pages: 1-18, ISSN: 2041-1723

The host-microbiota co-metabolite trimethylamine N-oxide (TMAO) is linked to increased cardiovascular risk but how its circulating levels are regulated remains unclear. We applied “explainable” machine learning, univariate, multivariate and mediation analyses of fasting plasma TMAO concentration and a multitude of phenotypes in 1,741 adult Europeans of the MetaCardis study. Here we show that next to age, kidney function is the primary variable predicting circulating TMAO, with microbiota composition and diet playing minor, albeit significant, roles. Mediation analysis suggests a causal relationship between TMAO and kidney function that we corroborate in preclinical models where TMAO exposure increases kidney scarring. Consistent with our findings, patients receiving glucose-lowering drugs with reno-protective properties have significantly lower circulating TMAO when compared to propensity-score matched control individuals. Our analyses uncover a bidirectional relationship between kidney function and TMAO that can potentially be modified by reno-protective anti-diabetic drugs and suggest a clinically actionable intervention for decreasing TMAO-associated excess cardiovascular risk.

Journal article

Roper KJ, Thomas J, Albalawi W, Maddocks E, Dobson S, Alshehri A, Barone FG, Baltazar M, Semple MG, Ho A, Turtle L, ISARIC4C Consortium, Paxton WA, Pollakis Get al., 2023, Quantifying neutralising antibody responses against SARS-CoV-2 in dried blood spots (DBS) and paired sera, Scientific Reports, Vol: 13, ISSN: 2045-2322

The ongoing SARS-CoV-2 pandemic was initially managed by non-pharmaceutical interventions such as diagnostic testing, isolation of positive cases, physical distancing and lockdowns. The advent of vaccines has provided crucial protection against SARS-CoV-2. Neutralising antibody (nAb) responses are a key correlate of protection, and therefore measuring nAb responses is essential for monitoring vaccine efficacy. Fingerstick dried blood spots (DBS) are ideal for use in large-scale sero-surveillance because they are inexpensive, offer the option of self-collection and can be transported and stored at ambient temperatures. Such advantages also make DBS appealing to use in resource-limited settings and in potential future pandemics. In this study, nAb responses in sera, venous blood and fingerstick blood stored on filter paper were measured. Samples were collected from SARS-CoV-2 acutely infected individuals, SARS-CoV-2 convalescent individuals and SARS-CoV-2 vaccinated individuals. Good agreement was observed between the nAb responses measured in eluted DBS and paired sera. Stability of nAb responses was also observed in sera stored on filter paper at room temperature for 28 days. Overall, this study provides support for the use of filter paper as a viable sample collection method to study nAb responses.

Journal article

Goldswain H, Dong X, Penrice-Randal R, Alruwaili M, Shawli GT, Prince T, Williamson MK, Raghwani J, Randle N, Jones B, Donovan-Banfield I, Salguero FJ, Tree JA, Hall Y, Hartley C, Erdmann M, Bazire J, Jearanaiwitayakul T, Semple MG, Openshaw PJM, Baillie JK, ISARIC4C Investigators, Emmett SR, Digard P, Matthews DA, Turtle L, Darby AC, Davidson AD, Carroll MW, Hiscox JAet al., 2023, The P323L substitution in the SARS-CoV-2 polymerase (NSP12) confers a selective advantage during infection, Genome Biology, Vol: 24, ISSN: 1474-7596

BACKGROUND: The mutational landscape of SARS-CoV-2 varies at the dominant viral genome sequence and minor genomic variant population. During the COVID-19 pandemic, an early substitution in the genome was the D614G change in the spike protein, associated with an increase in transmissibility. Genomes with D614G are accompanied by a P323L substitution in the viral polymerase (NSP12). However, P323L is not thought to be under strong selective pressure. RESULTS: Investigation of P323L/D614G substitutions in the population shows rapid emergence during the containment phase and early surge phase during the first wave. These substitutions emerge from minor genomic variants which become dominant viral genome sequence. This is investigated in vivo and in vitro using SARS-CoV-2 with P323 and D614 in the dominant genome sequence and L323 and G614 in the minor variant population. During infection, there is rapid selection of L323 into the dominant viral genome sequence but not G614. Reverse genetics is used to create two viruses (either P323 or L323) with the same genetic background. L323 shows greater abundance of viral RNA and proteins and a smaller plaque morphology than P323. CONCLUSIONS: These data suggest that P323L is an important contribution in the emergence of variants with transmission advantages. Sequence analysis of viral populations suggests it may be possible to predict the emergence of a new variant based on tracking the frequency of minor variant genomes. The ability to predict an emerging variant of SARS-CoV-2 in the global landscape may aid in the evaluation of medical countermeasures and non-pharmaceutical interventions.

Journal article

Liew F, Talwar S, Cross A, Willett B, Scott S, Logan N, Siggins M, Swieboda D, Sidhu J, Efstathiou C, Moore S, Davis C, Mohamed N, Nunag J, King C, Thompson AAR, Rowland-Jones S, Docherty A, Chalmers J, Ho L-P, Horsley A, Raman B, Poinasamy K, Marks M, Kon OM, Howard L, Wootton D, Dunachie S, Quint J, Evans R, Wain L, Fontanella S, de Silva T, Ho A, Harrison E, Baillie JK, Semple MG, Brightling C, Thwaites R, Turtle L, Openshaw Pet al., 2023, SARS-CoV-2-specific nasal IgA wanes 9 months after hospitalisation with COVID-19 and is not induced by subsequent vaccination, EBioMedicine, Vol: 87, Pages: 1-14, ISSN: 2352-3964

Background:Most studies of immunity to SARS-CoV-2 focus on circulating antibody, giving limited insights into mucosal defences that prevent viral replication and onward transmission. We studied nasal and plasma antibody responses one year after hospitalisation for COVID-19, including a period when SARS-CoV-2 vaccination was introduced.Methods:In this follow up study, plasma and nasosorption samples were prospectively collected from 446 adults hospitalised for COVID-19 between February 2020 and March 2021 via the ISARIC4C and PHOSP-COVID consortia. IgA and IgG responses to NP and S of ancestral SARS-CoV-2, Delta and Omicron (BA.1) variants were measured by electrochemiluminescence and compared with plasma neutralisation data.Findings:Strong and consistent nasal anti-NP and anti-S IgA responses were demonstrated, which remained elevated for nine months (p < 0.0001). Nasal and plasma anti-S IgG remained elevated for at least 12 months (p < 0.0001) with plasma neutralising titres that were raised against all variants compared to controls (p < 0.0001). Of 323 with complete data, 307 were vaccinated between 6 and 12 months; coinciding with rises in nasal and plasma IgA and IgG anti-S titres for all SARS-CoV-2 variants, although the change in nasal IgA was minimal (1.46-fold change after 10 months, p = 0.011) and the median remained below the positive threshold determined by pre-pandemic controls. Samples 12 months after admission showed no association between nasal IgA and plasma IgG anti-S responses (R = 0.05, p = 0.18), indicating that nasal IgA responses are distinct from those in plasma and minimally boosted by vaccination.Interpretation:The decline in nasal IgA responses 9 months after infection and minimal impact of subsequent vaccination may explain the lack of long-lasting nasal defence against reinfection and the limited effects of vaccination on transmission. These findings highlight the need to develop vaccines that enhance nasal immunity.Funding:This

Journal article

Fromentin S, Forslund SK, Chechi K, Aron-Wisnewsky J, Chakaroun R, Nielsen T, Tremaroli V, Ji B, Prifti E, Myridakis A, Chilloux J, Andrikopoulos P, Fan Y, Olanipekun MT, Alves R, Adiouch S, Bar N, Talmor-Barkan Y, Belda E, Caesar R, Coelho LP, Falony G, Fellahi S, Galan P, Galleron N, Helft G, Hoyles L, Isnard R, Le Chatelier E, Julienne H, Olsson L, Pedersen HK, Pons N, Quinquis B, Rouault C, Roume H, Salem J-E, Schmidt TSB, Vieira-Silva S, Li P, Zimmermann-Kogadeeva M, Lewinter C, Sondertoft NB, Hansen TH, Gauguier D, Gotze JP, Kober L, Kornowski R, Vestergaard H, Hansen T, Zucker J-D, Hercberg S, Letunic I, Backhed F, Oppert J-M, Nielsen J, Raes J, Bork P, Stumvoll M, Segal E, Clement K, Dumas M-E, Ehrlich SD, Pedersen Oet al., 2022, Microbiome and metabolome features of the cardiometabolic disease spectrum, Nature Medicine, Vol: 28, Pages: 303-+, ISSN: 1078-8956

Previous microbiome and metabolome analyses exploring non-communicable diseases have paid scant attention to major confounders of study outcomes, such as common, pre-morbid and co-morbid conditions, or polypharmacy. Here, in the context of ischemic heart disease (IHD), we used a study design that recapitulates disease initiation, escalation and response to treatment over time, mirroring a longitudinal study that would otherwise be difficult to perform given the protracted nature of IHD pathogenesis. We recruited 1,241 middle-aged Europeans, including healthy individuals, individuals with dysmetabolic morbidities (obesity and type 2 diabetes) but lacking overt IHD diagnosis and individuals with IHD at three distinct clinical stages—acute coronary syndrome, chronic IHD and IHD with heart failure—and characterized their phenome, gut metagenome and serum and urine metabolome. We found that about 75% of microbiome and metabolome features that distinguish individuals with IHD from healthy individuals after adjustment for effects of medication and lifestyle are present in individuals exhibiting dysmetabolism, suggesting that major alterations of the gut microbiome and metabolome might begin long before clinical onset of IHD. We further categorized microbiome and metabolome signatures related to prodromal dysmetabolism, specific to IHD in general or to each of its three subtypes or related to escalation or de-escalation of IHD. Discriminant analysis based on specific IHD microbiome and metabolome features could better differentiate individuals with IHD from healthy individuals or metabolically matched individuals as compared to the conventional risk markers, pointing to a pathophysiological relevance of these features.

Journal article

Talmor-Barkan Y, Bar N, Shaul AA, Shahaf N, Godneva A, Bussi Y, Lotan-Pompan M, Weinberger A, Shechter A, Chezar-Azerrad C, Arow Z, Hammer Y, Chechi K, Forslund SK, Fromentin S, Dumas M-E, Ehrlich SD, Pedersen O, Kornowski R, Segal Eet al., 2022, Metabolomic and microbiome profiling reveals personalized risk factors for coronary artery disease, NATURE MEDICINE, Vol: 28, Pages: 295-+, ISSN: 1078-8956

Journal article

Wickenhagen A, Sugrue E, Lytras S, Kuchi S, Noerenberg M, Turnbull ML, Loney C, Herder V, Allan J, Jarmson I, Cameron-Ruiz N, Varjak M, Pinto RM, Lee JY, Iselin L, Palmalux N, Stewart DG, Swingler S, Greenwood EJD, Crozier TWM, Gu Q, Davies EL, Clohisey S, Wang B, Maranhao Costa FT, Santana MF, de Lima Ferreira LC, Murphy L, Fawkes A, Meynert A, Grimes G, Filho JLDS, Marti M, Hughes J, Stanton RJ, Wang ECY, Ho A, Davis I, Jarrett RF, Castello A, Robertson DL, Semple MG, Openshaw PJM, Palmarini M, Lehner PJ, Baillie JK, Rihn SJ, Wilson SJet al., 2021, A prenylated dsRNA sensor protects against severe COVID-19, Science, Vol: 374, Pages: 1-18, ISSN: 0036-8075

Journal article

COVID-19 Host Genetics Initiative, 2021, Mapping the human genetic architecture of COVID-19, Nature, Vol: 600, Pages: 472-477, ISSN: 0028-0836

The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-191,2, host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases3-7. They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease.

Journal article

Chechi K, Vijay J, Voisine P, Mathieu P, Bosse Y, Tchernof A, Grundberg E, Richard Det al., 2019, <i>UCP1</i> expression-associated gene signatures of human epicardial adipose tissue, JCI INSIGHT, Vol: 4

Journal article

Chechi K, Lichtenbelt WVM, Richard D, 2018, Brown and beige adipose tissues: phenotype and metabolic potential in mice and men, JOURNAL OF APPLIED PHYSIOLOGY, Vol: 124, Pages: 482-496, ISSN: 8750-7587

Journal article

Chechi K, Voisine P, Mathieu P, Laplante M, Bonnet S, Picard F, Joubert P, Richard Det al., 2017, Functional characterization of the <i>Ucp1</i>-associated oxidative phenotype of human epicardial adipose tissue, SCIENTIFIC REPORTS, Vol: 7, ISSN: 2045-2322

Journal article

Labbe SM, Caron A, Chechi K, Laplante M, Lecomte R, Richard Det al., 2016, Metabolic activity of brown, "beige," and white adipose tissues in response to chronic adrenergic stimulation in male mice, AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, Vol: 311, Pages: E260-E268, ISSN: 0193-1849

Journal article

Chechi K, Richard D, 2015, Thermogenic potential and physiological relevance of human epicardial adipose tissue., Int J Obes Suppl, Vol: 5, Pages: S28-S34, ISSN: 2046-2166

Epicardial adipose tissue is a unique fat depot around the heart that shares a close anatomic proximity and vascular supply with the myocardium and coronary arteries. Its accumulation around the heart, measured using various imaging modalities, has been associated with the onset and progression of coronary artery disease in humans. Epicardial adipose tissue is also the only fat depot around the heart that is known to express uncoupling protein 1 at both mRNA and protein levels in the detectable range. Recent advances have further indicated that human epicardial fat exhibits beige fat-like features. Here we provide an overview of the physiological and pathophysiological relevance of human epicardial fat, and further discuss whether its thermogenic properties can serve as a target for the therapeutic management of coronary heart disease in humans.

Journal article

Chechi K, Nedergaard J, Richard D, 2014, Brown adipose tissue as an anti-obesity tissue in humans, OBESITY REVIEWS, Vol: 15, Pages: 92-106, ISSN: 1467-7881

Journal article

Chechi K, Blanchard P-G, Mathieu P, Deshaies Y, Richard Det al., 2013, Brown fat like gene expression in the epicardial fat depot correlates with circulating HDL-cholesterol and triglycerides in patients with coronary artery disease, INTERNATIONAL JOURNAL OF CARDIOLOGY, Vol: 167, Pages: 2264-2270, ISSN: 0167-5273

Journal article

Chechi K, Carpentier AC, Richard D, 2013, Understanding the brown adipocyte as a contributor to energy homeostasis, TRENDS IN ENDOCRINOLOGY AND METABOLISM, Vol: 24, Pages: 408-420, ISSN: 1043-2760

Journal article

Chechi K, Gelinas Y, Mathieu P, Deshaies Y, Richard Det al., 2012, Validation of Reference Genes for the Relative Quantification of Gene Expression in Human Epicardial Adipose Tissue, PLOS ONE, Vol: 7, ISSN: 1932-6203

Journal article

Richard D, Monge-Roffarello B, Chechi K, Labbé SM, Turcotte EEet al., 2012, Control and physiological determinants of sympathetically mediated brown adipose tissue thermogenesis., Front Endocrinol (Lausanne), Vol: 3

Brown adipose tissue (BAT) represents a remarkable heat-producing tissue. The thermogenic potential of BAT is conferred by uncoupling protein 1, a protein found uniquely in brown adipocytes. BAT activity and capacity is controlled by the sympathetic nervous system (SNS), which densely innervates brown fat depots. SNS-mediated BAT thermogenesis is essentially governed by hypothalamic and brainstem neurons. BAT activity is also modulated by brain energy balance pathways including the very significant brain melanocortin system, suggesting a genuine involvement of SNS-mediated BAT thermogenesis in energy homeostasis. The use of positron emission tomography/computed tomography scanning has revealed the presence of well-defined BAT depots in the cervical, clavicular, and paraspinal areas in adult humans. The prevalence of these depots is higher in subjects exposed to low temperature and is also higher in women compared to men. Moreover, the prevalence of BAT decreases with age and body fat mass, suggesting that BAT could be involved in energy balance regulation and obesity in humans. This short review summarizes recent progress made in our understanding of the control of SNS-mediated BAT thermogenesis and of the determinants of BAT prevalence or detection in humans.

Journal article

Chechi K, Yasui N, Ikeda K, Yamori Y, Cheema SKet al., 2010, Flax oil-mediated activation of PPAR-γ correlates with reduction of hepatic lipid accumulation in obese spontaneously hypertensive/NDmcr-cp rats, a model of the metabolic syndrome, BRITISH JOURNAL OF NUTRITION, Vol: 104, Pages: 1313-1321, ISSN: 0007-1145

Journal article

Chechi K, Herzberg GR, Cheema SK, 2010, Maternal dietary fat intake during gestation and lactation alters tissue fatty acid composition in the adult offspring of C57Bl/6 mice, PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS, Vol: 83, Pages: 97-104, ISSN: 0952-3278

Journal article

Chechi K, McGuire JJ, Cheema SK, 2010, An interaction of the pre- and post-weaning diets rich in omega-6 polyunsaturated fats alters plasma lipids, hepatic gene expression and aortic vascular reactivity in adult C57BL/6 mice., Nutr Metab Insights, Vol: 3, Pages: 69-78, ISSN: 1178-6388

AIM: To investigate the effects of diets rich in n-6 polyunsaturated fats (PUFA) fed during pre- and post-weaning time periods on the lipid metabolism and vascular reactivity in adult C57Bl/6 mice, in order to assess the impact of maternal nutrition and its interaction with the offspring diet on the metabolism of adult offspring. METHODS: Female C57Bl/6 mice were fed a high-fat diet enriched with n-6 PUFA (P) or control diet (C) for 2-weeks before, during mating, gestation and lactation, while their pups received either P or C for 8-weeks post-weaning. RESULTS: A significant interaction between the maternal and post-weaning diets was observed for the offspring body weight, food-, caloric-intake, plasma lipids, hepatic mRNA expression of lecithin cholesterol acyltransferase, aortic contractile and relaxation responses (P < 0.05). CONCLUSION: The overall metabolic and physiological outcome in the offspring is dependent upon the interaction between the pre- and post-weaning dietary environments.

Journal article

Chechi K, McGuire JJ, Cheema SK, 2009, Developmental programming of lipid metabolism and aortic vascular function in C57BL/6 mice: a novel study suggesting an involvement of LDL-receptor. (vol 296, pg R1029, 2009), AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY, Vol: 297, Pages: R911-R911, ISSN: 0363-6119

Journal article

Chechi K, McGuire JJ, Cheema SK, 2009, Developmental programming of lipid metabolism and aortic vascular function in C57BL/6 mice: a novel study suggesting an involvement of LDL-receptor, AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY, Vol: 296, Pages: R1029-R1040, ISSN: 0363-6119

Journal article

Chechi K, Cheema SK, 2006, Maternal diet rich in saturated fats has deleterious effects on plasma lipids of mice., Exp Clin Cardiol, Vol: 11, Pages: 129-135, ISSN: 1205-6626

BACKGROUND AND OBJECTIVES: High dietary fat intake has been reported to cause an alteration in lipid metabolism that is associated with an increased risk of cardiovascular disease. In the present study, an animal model was used to evaluate the effects of feeding diets rich in different fatty acids to mothers during pregnancy and lactation, and the effects of the maternal diet on parameters of lipid metabolism in adult offspring. The interaction between the offspring's own diet and the programming due to the maternal diet was also evaluated. METHODS: Female C57BL/6 mice were fed a high-fat diet (20% fat [weight to weight]) rich in either saturated fatty acids (SFA) or polyunsaturated fatty acids (PUFA) for two weeks before mating, during pregnancy and until weaning. The offspring were divided into two groups; each group was fed a high-fat diet enriched in either SFA or PUFA for eight weeks after weaning. The groups were designated as SFA/SFA (diet of the mother/diet of the offspring), SFA/PUFA, PUFA/PUFA and PUFA/SFA. Blood and tissues were collected at the end of the eight-week feeding period after an overnight fast. RESULTS: The plasma total cholesterol and low density lipoprotein cholesterol concentrations were significantly higher in the SFA/SFA group than in all other groups, whereas the PUFA/PUFA group had the lowest total cholesterol and low density lipoprotein cholesterol concentrations. Plasma high density lipoprotein cholesterol concentrations were significantly higher in the PUFA/SFA group than in the PUFA/PUFA and SFA/PUFA groups, whereas plasma triglyceride concentrations were not different among the groups. CONCLUSIONS: The data suggest that high maternal dietary fat intake during pregnancy affects lipid metabolism in the adult offspring. However, it appears that the offspring's own diet is also important in maintaining the regulation of lipid metabolism.

Journal article

Chechi K, McGuire JJ, Cheema SK, 2005, Effect of high fat maternal diet in the fetal programming of metabolic disorders, 3rd International Congress on Developmental Origins of Health and Disease, Publisher: INT PEDIATRIC RESEARCH FOUNDATION, INC, Pages: 1109-1109, ISSN: 0031-3998

Conference paper

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