Imperial College London

DrMarioFalchi

Faculty of MedicineDepartment of Immunology and Inflammation

Honorary Senior Research Fellow
 
 
 
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Contact

 

+44 (0)20 7594 6519m.falchi

 
 
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Location

 

Burlington-Danes Building, Room E303Hammersmith HospitalHammersmith Campus

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Summary

 

Publications

Publication Type
Year
to

138 results found

Visconti A, Rossi N, Deris H, Lee KA, Hanic M, Trbojevic-Akmacic I, Thomas AM, Bolte LA, Bjork JR, Hooiveld-Noeken JS, Board R, Harland M, Newton-Bishop J, Harries M, Sacco JJ, Lorigan P, Shaw HM, de Vries EGE, Fehrmann RSN, Weersma RK, Spector TD, Nathan P, Hospers GAP, Sasieni P, Bataille V, Lauc G, Falchi Met al., 2023, Total serum N-glycans associate with response to immune checkpoint inhibition therapy and survival in patients with advanced melanoma, BMC CANCER, Vol: 23

Journal article

Valles-Colomer M, Blanco-Míguez A, Manghi P, Asnicar F, Dubois L, Golzato D, Armanini F, Cumbo F, Huang KD, Manara S, Masetti G, Pinto F, Piperni E, Punčochář M, Ricci L, Zolfo M, Farrant O, Goncalves A, Selma-Royo M, Binetti AG, Becerra JE, Han B, Lusingu J, Amuasi J, Amoroso L, Visconti A, Steves CM, Falchi M, Filosi M, Tett A, Last A, Xu Q, Qin N, Qin H, May J, Eibach D, Corrias MV, Ponzoni M, Pasolli E, Spector TD, Domenici E, Collado MC, Segata Net al., 2023, The person-to-person transmission landscape of the gut and oral microbiomes., Nature, Vol: 614, Pages: 125-135

The human microbiome is an integral component of the human body and a co-determinant of several health conditions1,2. However, the extent to which interpersonal relations shape the individual genetic makeup of the microbiome and its transmission within and across populations remains largely unknown3,4. Here, capitalizing on more than 9,700 human metagenomes and computational strain-level profiling, we detected extensive bacterial strain sharing across individuals (more than 10 million instances) with distinct mother-to-infant, intra-household and intra-population transmission patterns. Mother-to-infant gut microbiome transmission was considerable and stable during infancy (around 50% of the same strains among shared species (strain-sharing rate)) and remained detectable at older ages. By contrast, the transmission of the oral microbiome occurred largely horizontally and was enhanced by the duration of cohabitation. There was substantial strain sharing among cohabiting individuals, with 12% and 32% median strain-sharing rates for the gut and oral microbiomes, and time since cohabitation affected strain sharing more than age or genetics did. Bacterial strain sharing additionally recapitulated host population structures better than species-level profiles did. Finally, distinct taxa appeared as efficient spreaders across transmission modes and were associated with different predicted bacterial phenotypes linked with out-of-host survival capabilities. The extent of microorganism transmission that we describe underscores its relevance in human microbiome studies5, especially those on non-infectious, microbiome-associated diseases.

Journal article

Zhang X, Adebayo AS, Wang D, Raza Y, Tomlinson M, Dooley H, Bowyer RCE, Small KS, Steves CJ, Spector TD, Duncan EL, Visconti A, Falchi Met al., 2022, PPI-Induced Changes in Plasma Metabolite Levels Influence Total Hip Bone Mineral Density in a UK Cohort, JOURNAL OF BONE AND MINERAL RESEARCH, ISSN: 0884-0431

Journal article

Surendran P, Stewart ID, Yeung VPWA, Pietzner M, Raffler J, Worheide MA, Li C, Smith RF, Wittemans LBL, Bomba L, Menni C, Zierer J, Rossi N, Sheridan PA, Watkins NA, Mangino M, Hysi PG, Di Angelantonio E, Falchi M, Spector TD, Soranzo N, Michelotti GA, Arlt W, Lotta LA, Denaxas S, Hemingway H, Gamazon ER, Howson JMM, Wood AM, Danesh J, Wareham NJ, Kastenmueller G, Fauman EB, Suhre K, Butterworth AS, Langenberg Cet al., 2022, Rare and common genetic determinants of metabolic individuality and their effects on human health, Nature Medicine, Vol: 28, Pages: 2321-2332, ISSN: 1078-8956

Garrod’s concept of ‘chemical individuality’ has contributed to comprehension of the molecular origins of human diseases. Untargeted high-throughput metabolomic technologies provide an in-depth snapshot of human metabolism at scale. We studied the genetic architecture of the human plasma metabolome using 913 metabolites assayed in 19,994 individuals and identified 2,599 variant–metabolite associations (P < 1.25 × 10−11) within 330 genomic regions, with rare variants (minor allele frequency ≤ 1%) explaining 9.4% of associations. Jointly modeling metabolites in each region, we identified 423 regional, co-regulated, variant–metabolite clusters called genetically influenced metabotypes. We assigned causal genes for 62.4% of these genetically influenced metabotypes, providing new insights into fundamental metabolite physiology and clinical relevance, including metabolite-guided discovery of potential adverse drug effects (DPYD and SRD5A2). We show strong enrichment of inborn errors of metabolism-causing genes, with examples of metabolite associations and clinical phenotypes of non-pathogenic variant carriers matching characteristics of the inborn errors of metabolism. Systematic, phenotypic follow-up of metabolite-specific genetic scores revealed multiple potential etiological relationships.

Journal article

Coradduzza D, Solinas T, Balzano F, Culeddu N, Rossi N, Cruciani S, Azara E, Maioli M, Zinellu A, De Miglio MR, Madonia M, Falchi M, Carru Cet al., 2022, miRNAs as Molecular Biomarkers for Prostate Cancer, JOURNAL OF MOLECULAR DIAGNOSTICS, Vol: 24, Pages: 1171-1180, ISSN: 1525-1578

Journal article

Visconti A, Murray B, Rossi N, Wolf J, Ourselin S, Spector TD, Freeman EE, Bataille V, Falchi Met al., 2022, Cutaneous manifestations of SARS-CoV-2 infection during the Delta and Omicron waves in 348 691 UK users of the UK ZOE COVID Study app, BRITISH JOURNAL OF DERMATOLOGY, ISSN: 0007-0963

Journal article

Patasova K, Haarman AEG, Musolf AM, Mahroo OA, Rahi JS, Falchi M, Verhoeven VJM, Bailey-Wilson JE, Klaver CCW, Duggal P, Klein A, Guggenheim JA, Hammond CJ, Hysi PGet al., 2022, Association analyses of rare variants identify two genes associated with refractive error, PLOS ONE, Vol: 17, ISSN: 1932-6203

Journal article

Rossi N, Lee KA, Bermudez M, Visconti A, Thomas AM, Bolte LA, Bjork JR, Ruijter LKD, Newton-Bishop J, Harland M, Shaw HM, Harries M, Sacco J, Board R, Lorigan P, Vries EGED, Segata N, Taams L, Papa S, Spector TD, Nathan P, Weersma RK, Hospers GAP, Fehrmann RSN, Bataille V, Falchi Met al., 2022, Circulating inflammatory proteins associate with response to immune checkpoint inhibition therapy in patients with advanced melanoma, EBIOMEDICINE, Vol: 83, ISSN: 2352-3964

Journal article

Moustafa JSE-S, Jackson AU, Brotman SM, Guan L, Villicana S, Roberts AL, Zito A, Bonnycastle L, Erdos MR, Narisu N, Stringham HM, Welch R, Yan T, Lakka T, Parker S, Tuomilehto J, Seow J, Graham C, Huettner I, Acors S, Kouphou N, Wadge S, Duncan EL, Steves CJ, Doores KJ, Malim MH, Collins FS, Pajukanta P, Boehnke M, Koistinen HA, Laakso M, Falchi M, Bell JT, Scott LJ, Mohlke KL, Small KSet al., 2022, ACE2 expression in adipose tissue is associated with cardio-metabolic risk factors and cell type composition-implications for COVID-19, INTERNATIONAL JOURNAL OF OBESITY, Vol: 46, Pages: 1478-1486, ISSN: 0307-0565

Journal article

Patasova K, Khawaja AP, Wojciechowski R, Mahroo OA, Falchi M, Rahi JS, Hammond CJ, Hysi PGet al., 2022, A genome-wide analysis of 340 318 participants identifies four novel loci associated with the age of first spectacle wear, HUMAN MOLECULAR GENETICS, Vol: 31, Pages: 3012-3019, ISSN: 0964-6906

Journal article

Le Roy CI, Kurilshikov A, Leeming ER, Visconti A, Bowyer RCE, Menni C, Fachi M, Koutnikova H, Veiga P, Zhernakova A, Derrien M, Spector TDet al., 2022, Yoghurt consumption is associated with changes in the composition of the human gut microbiome and metabolome, BMC MICROBIOLOGY, Vol: 22, ISSN: 1471-2180

Journal article

Hysi PG, Mangino M, Christofidou P, Falchi M, Karoly ED, Mohney RP, Valdes AM, Spector TD, Menni Cet al., 2022, Metabolome Genome-Wide Association Study Identifies 74 Novel Genomic Regions Influencing Plasma Metabolites Levels, METABOLITES, Vol: 12

Journal article

Grosche S, Marenholz I, Esparza-Gordillo J, Arnau-Soler A, Pairo-Castineira E, Rueschendorf F, Ahluwalia TS, Almqvist C, Arnold A, Baurecht H, Bisgaard H, Bonnelykke K, Brown SJ, Bustamante M, Curtin JA, Custovic A, Dharmage SC, Esplugues A, Falchi M, Fernandez-Orth D, Ferreira MAR, Franke A, Gerdes S, Gieger C, Hakonarson H, Holt PG, Homuth G, Hubner N, Hysi PG, Jarvelin M-R, Karlsson R, Koppelman GH, Lau S, Lutz M, Magnusson PKE, Marks GB, Mueller-Nurasyid M, Noethen MM, Paternoster L, Pennell CE, Peters A, Rawlik K, Robertson CF, Rodriguez E, Sebert S, Simpson A, Sleiman PMA, Standl M, Stoelzl D, Strauch K, Szwajda A, Tenesa A, Thompson PJ, Ullemar V, Visconti A, Vonk JM, Wang CA, Weidinger S, Wielscher M, Worth CL, Xu C-J, Lee Y-Aet al., 2021, Rare variant analysis in eczema identifies exonic variants in DUSP1, NOTCH4 and SLC9A4, NATURE COMMUNICATIONS, Vol: 12

Journal article

Dotz V, Visconti A, Lomax-Browne HJ, Clerc F, Hipgrave Ederveen AL, Medjeral-Thomas NR, Cook HT, Pickering MC, Wuhrer M, Falchi Met al., 2021, O- and N-glycosylation of serum immunoglobulin A is associated with IgA nephropathy and glomerular function., Journal of the American Society of Nephrology, Vol: 32, Pages: 1-12, ISSN: 1046-6673

BACKGROUND: IgA nephropathy (IgAN) is the most common primary glomerular disease worldwide and is a leading cause of renal failure. The disease mechanisms are not completely understood, but a higher abundance of galactose-deficient IgA is recognized to play a crucial role in IgAN pathogenesis. Although both types of human IgA (IgA1 and IgA2) have several N-glycans as post-translational modification, only IgA1 features extensive hinge-region O-glycosylation. IgA1 galactose deficiency on the O-glycans is commonly detected by a lectin-based method. To date, limited detail is known about IgA O- and N-glycosylation in IgAN. METHODS: To gain insights into the complex O- and N-glycosylation of serum IgA1 and IgA2 in IgAN, we used liquid chromatography-mass spectrometry (LC-MS) for the analysis of tryptic glycopeptides of serum IgA from 83 patients with IgAN and 244 age- and sex-matched healthy controls. RESULTS: Multiple structural features of N-glycosylation of IgA1 and IgA2 were associated with IgAN and glomerular function in our cross-sectional study. These features included differences in galactosylation, sialylation, bisection, fucosylation, and N-glycan complexity. Moreover, IgA1 O-glycan sialylation was associated with both the disease and glomerular function. Finally, glycopeptides were a better predictor of IgAN and glomerular function than galactose-deficient IgA1 levels measured by lectin-based ELISA. CONCLUSIONS: Our high-resolution data suggest that IgA O- and N-glycopeptides are promising targets for future investigations on the pathophysiology of IgAN and as potential noninvasive biomarkers for disease prediction and deteriorating kidney function.

Journal article

Cvetko A, Mangino M, Tijardovic M, Kifer D, Falchi M, Keser T, Perola M, Spector TD, Lauc G, Menni C, Gornik Oet al., 2021, Plasma N-glycome shows continuous deterioration as the diagnosis of insulin resistance approaches, BMJ OPEN DIABETES RESEARCH & CARE, Vol: 9

Journal article

Hopkinson N, Rossi N, El-Sayed Moustafa JS, Laverty A, Quint J, Freidin MB, Visconti A, Murray B, Modat M, Ourselin S, Small K, Davies R, Wolf J, Spector TD, Steves CJ, Falchi Met al., 2021, Current smoking and COVID-19 risk: results from a population symptom app in over 2.4 million people, Thorax, Vol: 76, Pages: 714-722, ISSN: 0040-6376

Background: The association between current tobacco smoking, the risk of developing symptomatic COVID-19 and the severity of illness is an important information gap.Methods: UK users of the Zoe COVID Symptom Study App provided baseline data including demographics, anthropometrics, smoking status and medical conditions, and were asked to log their condition daily. Participants who reported that they did not feel physically normal were then asked by the app to complete a series of questions, including 14 potential COVID-19 symptoms and about hospital attendance. The main study outcome was the development of “classic” symptoms of COVID-19 during the pandemic defined as fever, new persistent cough and breathlessness and their association with current smoking. The number of concurrent COVID-19 symptoms was used as a proxy for severity and the pattern of association between symptoms was also compared between smokers and non-smokers. Results: Between 24th March 2020 to 23rd April 2020, data were available on 2,401,982 participants, mean(SD) age 43.6(15.1) years, 63.3% female, overall smoking prevalence 11.0%. 834,437 (35%) participants reported being unwell and entered one or more symptoms. Current smokers were more likely to report symptoms suggesting a diagnosis of COVID-19; classic symptoms adjusted OR[95%CI] 1.14[1.10 to 1.18]; >5 symptoms 1.29[1.26 to 1.31]; >10 symptoms 1.50[1.42 to 1.58]. The pattern of association between reported symptoms did not vary between smokers and non-smokers.Interpretation: These data are consistent with people who smoke being at an increased risk of developing symptomatic COVID-19.

Journal article

Greto VL, Cvetko A, Stambuk T, Dempster NJ, Kifer D, Deris H, Cindric A, Vuckovic F, Falchi M, Gillies RS, Tomlinson JW, Gornik O, Sgromo B, Spector TD, Menni C, Geremia A, Arancibia-Carcamo CV, Lauc Get al., 2021, Extensive weight loss reduces glycan age by altering IgG N-glycosylation, INTERNATIONAL JOURNAL OF OBESITY, Vol: 45, Pages: 1521-1531, ISSN: 0307-0565

Journal article

Sanna M, Li X, Visconti A, Freidin MB, Sacco C, Ribero S, Hysi P, Bataille V, Han J, Falchi Met al., 2021, Looking for Sunshine: Genetic Predisposition to Sun Seeking in 265,000 Individuals of European Ancestry, JOURNAL OF INVESTIGATIVE DERMATOLOGY, Vol: 141, Pages: 779-786, ISSN: 0022-202X

Journal article

Piaggeschi G, Rolla S, Rossi N, Brusa D, Naccarati A, Couvreur S, Spector TD, Roederer M, Mangino M, Cordero F, Falchi M, Visconti Aet al., 2021, Immune Trait Shifts in Association With Tobacco Smoking: A Study in Healthy Women, FRONTIERS IN IMMUNOLOGY, Vol: 12, ISSN: 1664-3224

Journal article

Visconti A, Bataille V, Rossi N, Kluk J, Murphy R, Puig S, Nambi R, Bowyer RCE, Murray B, Bournot A, Wolf J, Ourselin S, Steves CJ, Spector TD, Falchi Met al., 2021, Diagnostic value of cutaneous manifestation of SARS-CoV-2 infection, BRITISH JOURNAL OF DERMATOLOGY, Vol: 184, Pages: 880-887, ISSN: 0007-0963

Journal article

Sudre CH, Lee KA, Lochlainn MN, Varsavsky T, Murray B, Graham MS, Menni C, Modat M, Bowyer RCE, Nguyen LH, Drew DA, Joshi AD, Ma W, Guo C-G, Lo C-H, Ganesh S, Buwe A, Pujol JC, du Cadet JL, Visconti A, Freidin MB, Moustafa JSE-S, Falchi M, Davies R, Gomez MF, Fall T, Cardoso MJ, Wolf J, Franks PW, Chan AT, Spector TD, Steves CJ, Ourselin Set al., 2021, Symptom clusters in COVID-19: A potential clinical prediction tool from the COVID Symptom Study app, SCIENCE ADVANCES, Vol: 7, ISSN: 2375-2548

Journal article

Rossi N, Aliyev E, Visconti A, Akil ASA, Syed N, Aamer W, Padmajeya SS, Falchi M, Fakhro KAet al., 2021, Ethnic-specific association of amylase gene copy number with adiposity traits in a large Middle Eastern biobank, NPJ GENOMIC MEDICINE, Vol: 6

Journal article

Patasova K, Khawaja AP, Tamraz B, Williams KM, Mahroo OA, Freidin M, Solebo AL, Vehof J, Falchi M, Rahi JS, Hammond CJ, Hysi PGet al., 2021, Association Between Medication-Taking and Refractive Error in a Large General Population-Based Cohort, INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, Vol: 62, ISSN: 0146-0404

Journal article

He J-W, Zhou X-J, Li Y-F, Wang Y-N, Liu L-J, Shi S-F, Xin X-H, Li R-S, Falchi M, Lv J-C, Zhang Het al., 2021, Associations of Genetic Variants Contributing to Gut Microbiota Composition in Immunoglobin A Nephropathy, MSYSTEMS, Vol: 6, ISSN: 2379-5077

Journal article

Williams FMK, Freidin MB, Mangino M, Couvreur S, Visconti A, Bowyer RCE, Le Roy CI, Falchi M, Mompeo O, Sudre C, Davies R, Hammond C, Menni C, Steves CJ, Spector TDet al., 2020, Self-Reported Symptoms of COVID-19, Including Symptoms Most Predictive of SARS-CoV-2 Infection, Are Heritable, TWIN RESEARCH AND HUMAN GENETICS, Vol: 23, Pages: 316-321, ISSN: 1832-4274

Journal article

Bar N, Korem T, Weissbrod O, Zeevi D, Rothschild D, Leviatan S, Kosower N, Lotan-Pompan M, Weinberger A, Le Roy CI, Menni C, Visconti A, Falchi M, Spector TD, Adamski J, Franks PW, Pedersen O, Segal Eet al., 2020, A reference map of potential determinants for the human serum metabolome, NATURE, Vol: 588, Pages: 135-140, ISSN: 0028-0836

Journal article

Bataille V, Visconti A, Rossi N, Murray B, Bournot A, Wolf J, Ourselin S, Steves C, Spector TD, Falchi Met al., 2020, Diagnostic value of skin manifestation of SARS-CoV-2 infection

<jats:title>Abstract</jats:title><jats:p>SARS-CoV-2 causes multiple immune-related reactions at various stages of the disease. The wide variety of skin presentations has delayed linking these to the virus. Previous studies had attempted to look at the prevalence and timing of SARS-COV-2 rashes but were based on mostly hospitalized severe cases and had little follow up. Using data collected on a subset of 336,847 eligible UK users of the COVID Symptom Study app, we observed that 8.8% of the swab positive cases (total: 2,021 subjects) reported either a body rash or an acral rash, compared to 5.4% of those with a negative swab test (total: 25,136). Together, these two skin presentations showed an odds ratio (OR) of 1.67 (95% confidence interval [CI]: 1.41-1.96) for being swab positive. Skin rashes were also predictive in the larger untested group of symptomatic app users (N=54,652), as 8.2% of those who had reported at least one classical COVID-19 symptom, <jats:italic>i</jats:italic>.<jats:italic>e</jats:italic>., fever, persistent cough, and/or anosmia, also reported a rash. Data from an independent online survey of 11,546 respondents with a rash showed that in 17% of swab positive cases, the rash was the initial presentation. Furthermore, in 21%, the rash was the only clinical sign. Skin rashes cluster with other COVID-19 symptoms, are predictive of a positive swab test and occur in a significant number of cases, either alone or before other classical symptoms. Recognising rashes is important in identifying new and earlier COVID-19 cases.</jats:p>

Journal article

Menni C, Valdes AM, Freidin MB, Sudre CH, Nguyen LH, Drew DA, Ganesh S, Varsavsky T, Cardoso MJ, Moustafa JSE-S, Visconti A, Hysi P, Bowyer RCE, Mangino M, Falchi M, Wolf J, Ourselin S, Chan AT, Steves CJ, Spector TDet al., 2020, Real-time tracking of self-reported symptoms to predict potential COVID-19, NATURE MEDICINE, Vol: 26, Pages: 1037-+, ISSN: 1078-8956

Journal article

Visconti A, Sanna M, Bataille V, Falchi Met al., 2020, Genetics plays a role in nevi distribution in women, MELANOMA MANAGEMENT, Vol: 7, Pages: 3-6, ISSN: 2045-0885

Journal article

Greto VL, Cvetko A, Štambuk T, Dempster NJ, Kifer D, Deriš H, Cindrić A, Vučković F, Falchi M, Gillies RS, Tomlinson JW, Gornik O, Sgromo B, Spector TD, Menni C, Geremia A, Arancibia-Cárcamo CV, Lauc Get al., 2020, Extensive weight loss can reduce immune age by altering IgG N-glycosylation

<jats:title>ABSTRACT</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Obesity is a major global health problem, and is associated with increased cardiometabolic morbidity and mortality. Protein glycosylation is a frequent postranslational modification, highly responsive to numerous pathophysiological conditions and ageing. The prospect of biological age reduction, by reverting glycosylation changes through metabolic intervention, opens many possibilities. We have investigated whether weight loss interventions affect inflammation- and ageing-associated IgG glycosylation changes, in a longitudinal cohort of bariatric surgery patients. To support potential findings, BMI-related glycosylation changes were monitored in a longitudinal twins cohort.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>IgG N-glycans were chromatographically profiled in 37 obese patients, subjected to low-calorie diet, followed by bariatric surgery, across multiple timepoints. Similarly, plasma-derived IgG N-glycan traits were longitudinally monitored in 1,680 participants from the TwinsUK cohort.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Low-calorie diet induced a marked decrease in the levels of IgG N-glycans with bisecting GlcNAc, whose higher levels are usually associated with ageing and inflammatory conditions. Bariatric surgery resulted in extensive alterations of the IgG glycome that accompanied progressive weight loss during one-year follow-up. We observed a significant increase in digalactosylated and sialylated glycans, and a substantial decrease in agalactosylated and core fucosylated IgG glycans. In general, this IgG glycan profile is associated with a younger biological age and reflects an enhanced anti-inflammatory IgG potential. Loss of BMI over a 20 year period in the TwinsUK cohort validated a weight loss-assoc

Journal article

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