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Nutrition in acute and chronic diseases

Food groups associated with immune-mediated inflammatory diseases: a Mendelian randomization and disease severity study

European Journal of Clinical Nutrition volume 75, pages 1368–1382 (2021)Cite this article

Subjects

Abstract

Background/Objectives

Immune-mediated inflammatory diseases (IMIDs) are prevalent diseases. There is, however, a lack of understanding of the link between diet and IMIDs, how much dietary patterns vary between them and if there are food groups associated with a worsening of the disease.

Subjects/Methods

To answer these questions we analyzed a nation-wide cohort of n = 11,308 patients from six prevalent IMIDs and 2050 healthy controls. We compared their weekly intake of the major food categories, and used a Mendelian randomization approach to determine which dietary changes are caused by disease. Within each IMID, we analyzed the association between food frequency and disease severity.

Results

After quality control, n = 11,230 recruited individuals were used in this study. We found that diet is profoundly altered in all IMIDs: at least three food categories are significantly altered in each disease (P < 0.05). Inflammatory bowel diseases showed the largest differences compared to controls (n ≥ 8 categories, P < 0.05). Mendelian randomization analysis supported that some of these dietary changes, like vegetable reduction in Crohn’s Disease (P = 2.5 × 10−10, OR(95% CI) = 0.73(0.65, 0.80)), are caused by the disease. Except for Psoriatic Arthritis and Systemic Lupus Erythematosus, we have found ≥2 food groups significantly associated with disease severity in the other IMIDs (P < 0.05).

Conclusions

This cross-disease study demonstrates that prevalent IMIDs are associated to a significant change in the normal dietary patterns. This variation is highly disease-specific and, in some cases, it is caused by the disease itself. Severity in IMIDs is also associated with specific food groups. The results of this study underscore the importance of studying diet in IMIDs.

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Acknowledgements

The IMID Consortium includes the following: Eduardo Fonseca, Jesús Rodríguez, Patricia Carreira, Valle García, José A. Pinto-Tasende, Lluís Puig, Elena Ricart, Francisco Blanco, Jordi Gratacós, Ricardo Blanco, Víctor Martínez Taboada, Emilia Fernández, Isidoro González, Fernando Gomollón García, Raimon Sanmartí, Ana Gutiérrez, Àlex Olivé, José Luís López Estebaranz, Esther García-Planella, Juan Carlos Torre-Alonso, José Luis Andreu, David Moreno Ramírez, Benjamín Fernández, Mª Ángeles Aguirre Zamorano, Pablo de la Cueva, Pilar Nos Mateu, Paloma Vela, Francisco Vanaclocha, Héctor Corominas, Santiago Muñoz, Joan Miquel Nolla, Enrique Herrera, Carlos González, José Luis Marenco de la Fuente, Maribel Vera, Alba Erra, Daniel Roig, Antonio Zea, María Esteve, Carlos Tomás, Pedro Zarco, José María Pego, Cristina Saro, Antonio González, Mercedes Freire, Alicia García, Elvira Díez, Georgina Salvador, César Díaz-Torne, Simón Sánchez, Alfredo Willisch Domínguez, José Antonio Mosquera, Julio Ramírez, Esther Rodríguez Almaraz, Núria Palau, Raül Tortosa, Mireia López, Andrea Pluma, Adrià Aterido. We would like to thank Dr Eduard Cabré for stimulating discussions.

IMID Consortium

Eduardo Fonseca17, Jesús Rodríguez18, Patricia Carreira19, Valle García20, José A. Pinto-Tasende21, Lluís Puig22, Elena Ricart23, Francisco Blanco24, Jordi Gratacós25, Ricardo Blanco26, Víctor Martínez Taboada26, Emilia Fernández27, Pablo Unamuno27, Isidoro González28, Fernando Gomollón García29, Raimon Sanmartí30, Ana Gutiérrez31, Àlex Olivé32, José Luís López Estebaranz33, Esther García-Planella34, Juan Carlos Torre-Alonso35, José Luis Andreu36, David Moreno Ramírez37, Benjamín Fernández38, Mª Ángeles Aguirre Zamorano39, Pablo de la Cueva40, Pilar Nos Mateu41, Paloma Vela42, Francisco Vanaclocha43, Héctor Coromines44, Santiago Muñoz45, Joan Miquel Nolla46, Enrique Herrera47, Carlos González48, José Luis Marenco de la Fuente49, Maribel Vera50, Alba Erra51, Daniel Roig52, Antonio Zea53, María Esteve Comas54, Carles Tomàs55, Pedro Zarco56, José María Pego57, Cristina Saro58, Antonio González59, Mercedes Freire60, Alicia García61, Elvira Díez62, Georgina Salvador63, César Díaz64, Simón Sánchez65, Alfredo Willisch Dominguez66, José Antonio Mosquera67, Julio Ramírez68, Esther Rodríguez Almaraz69, Núria Palau51, Raül Tortosa51, Mireia López51, Andrea Pluma51, Adrià Aterido51

Funding

This work was supported by the Spanish Ministry of Economy and Competitiveness grants (IPT-010000-2010-36, PSE-010000-2006-6, and PI12/01362).

Author information

Authors and Affiliations

  1. Rheumatology Research Group, Vall d’Hebron Hospital Research Institute, Barcelona, Spain

    Antonio Julià, Sergio H. Martínez-Mateu, Adrià Aterido, María López Lasanta & Sara Marsal

  2. Hospital Universitari Germans Trias i Pujol, Badalona, Spain

    Eugeni Domènech & Carlos Ferrándiz

  3. CIBERehd, Madrid, Spain

    Eugeni Domènech & Javier P. Gisbert

  4. Hospital Clínic de Barcelona and IDIBAPS, Barcelona, Spain

    Juan D. Cañete

  5. Hospital Universitario de Guadalajara, Guadalajara, Spain

    Jesús Tornero

  6. Hospital Universitario de La Princesa and IIS-IP, Madrid, Spain

    Javier P. Gisbert, Esteban Daudén & Santos Castañeda

  7. UGC Reumatología, Instituto de Investigación Biomédica (IBIMA), Hospital Regional Universitario de Málaga, Universidad de Málaga, Málaga, Spain

    Antonio Fernández-Nebro

  8. Hospital Clínico Universitario de Santiago, Santiago de Compostela, Spain

    Manuel Barreiro-de Acosta

  9. Hospital del Mar, Barcelona, Spain

    Carolina Pérez

  10. Hospital Universitario Central de Asturias, Oviedo, Spain

    Rubén Queiró & Mercedes Alpéri

  11. Hospital General Universitario Gregorio Marañón, Madrid, Spain

    Francisco Javier López-Longo

  12. Consorcio Hospital General Universitario de Valencia, Valencia, Spain

    José Luís Sánchez Carazo

  13. Hospital Clínico San Carlos, Madrid, Spain

    Juan Luís Mendoza

  14. Hospital Virgen de la Vega, Salamanca, Spain

    Carlos Montilla

  15. Hospital Universitario Virgen Macarena, Sevilla, Spain

    José Javier Pérez Venegas

  16. Complejo Asistencial Universitario de León, León, Spain

    Fernando Muñoz

  17. Dermatology Department, Complejo Hospitalario Universitario A Coruña, A Coruña, Spain

    Eduardo Fonseca

  18. Rheumatology Department, Hospital Universitari de Bellvitge, Barcelona, Spain

    Jesús Rodríguez

  19. Rheumatology Department, Hospital Universitario 12 de Octubre, Madrid, Spain

    Patricia Carreira

  20. Gastroenterology Department, Hospital Universitario Reina Sofía, Córdoba, Spain

    Valle García

  21. Rheumatology Department, Complejo Hospitalario Universitario A Coruña, A Coruña, Spain

    José A. Pinto-Tasende

  22. Dermatology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain

    Lluís Puig

  23. Gastroenterology Department, Fundació Clínic per a la Recerca Biomèdica, Barcelona, Spain

    Elena Ricart

  24. Rheumatology Department, Complejo Hospitalario Universitario A Coruña, A Coruña, Spain

    Francisco Blanco

  25. Rheumatology Department, Hospital Universitari Parc Taulí, Sabadell, Spain

    Jordi Gratacós

  26. Rheumatology Department, Hospital Universitario Marqués de Valdecilla, Santander, Spain

    Ricardo Blanco & Víctor Martínez Taboada

  27. Dermatology Department, Hospital Universitario de Salamanca, Salamanca, Spain

    Emilia Fernández & Pablo Unamuno

  28. Rheumatology Department, Hospital Universitario de La Princesa, Madrid, Spain

    Isidoro González

  29. Gastroenterology Department, Hospital Clínico Universitario Lozano Blesa, Zaragoza, Spain

    Fernando Gomollón García

  30. Rheumatology Department, Fundació Clínic per a la Recerca Biomèdica, Barcelona, Spain

    Raimon Sanmartí

  31. Gastroenterology Department, Hospital General Universitario de Alicante, Alicante, Spain

    Ana Gutiérrez

  32. Rheumatology Department, Hospital Universitari Germans Trias i Pujol, Badalona, Spain

    Àlex Olivé

  33. Dermatology Department, Hospital Universitario Fundación Alcorcón, Madrid, Spain

    José Luís López Estebaranz

  34. Gastroenterology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain

    Esther García-Planella

  35. Rheumatology Department, Hospital Monte Naranco, Oviedo, Spain

    Juan Carlos Torre-Alonso

  36. Rheumatology Department, Hospital Universitario Puerta de Hierro, Madrid, Spain

    José Luis Andreu

  37. Dermatology Department, Hospital Universitario Virgen Macarena, Sevilla, Spain

    David Moreno Ramírez

  38. Rheumatology Department, Hospital Clínico San Carlos, Madrid, Spain

    Benjamín Fernández

  39. Rheumatology Department, Hospital Universitario Reina Sofia, Córdoba, Spain

    Mª Ángeles Aguirre Zamorano

  40. Dermatology Department, Hospital Universitario Infanta Leonor, Madrid, Spain

    Pablo de la Cueva

  41. Gastroenterology Department, Hospital Clínico y Politécnico La Fe, Valencia, Spain

    Pilar Nos Mateu

  42. Rheumatology Department, Hospital General Universitario de Alicante, Alicante, Spain

    Paloma Vela

  43. Dermatology Department, Hospital Universitario 12 de Octubre, Madrid, Spain

    Francisco Vanaclocha

  44. Rheumatology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain

    Héctor Coromines

  45. Rheumatology Department, Hospital Universitario Infanta Sofía, Madrid, Spain

    Santiago Muñoz

  46. Rheumatology Department, Hospital Universitari de Bellvitge, Barcelona, Spain

    Joan Miquel Nolla

  47. Dermatology Department, Hospital Universitario Virgen de la Victoria, Málaga, Spain

    Enrique Herrera

  48. Rheumatology Department, Hospital General Universitario Gregorio Marañón, Madrid, Spain

    Carlos González

  49. Rheumatology Department, Hospital Universitario Virgen de Valme, Sevilla, Spain

    José Luis Marenco de la Fuente

  50. Gastroenterology Department, Hospital Universitario Puerta de Hierro, Madrid, Spain

    Maribel Vera

  51. Rheumatology Department, Hospital Universitari Vall d’Hebron, Barcelona, Spain

    Alba Erra, Núria Palau, Raül Tortosa, Mireia López, Andrea Pluma & Adrià Aterido

  52. Rheumatology Department, Centre d’Atenció Especialitzada Cornellà de Llobregat, Barcelona, Spain

    Daniel Roig

  53. Rheumatology Department, Hospital Universitario Ramón y Cajal, Madrid, Spain

    Antonio Zea

  54. Gastroenterology Department, Hospital Universitari MútuaTerrassa, Barcelona, Spain

    María Esteve Comas

  55. Rheumatology Department, Hospital Comarcal d’Amposta, Amposta, Spain

    Carles Tomàs

  56. Rheumatology Department, Hospital Universitario Fundación Alcorcón, Madrid, Spain

    Pedro Zarco

  57. Rheumatology Department, Hospital do Meixoeiro, Vigo, Spain

    José María Pego

  58. Internal Medicine Department, Hospital Universitario de Cabueñes, Gijón, Spain

    Cristina Saro

  59. Rheumatology Department, Hospital Clinico Universitario de Santiago, Santiago de Compostela, Spain

    Antonio González

  60. Rheumatology Department, Complejo Hospitalario Universitario A Coruña, A Coruña, Spain

    Mercedes Freire

  61. Rheumatology Department, Centro Periférico de Especialidades Virgen de los Reyes, Sevilla, Spain

    Alicia García

  62. Rheumatology Department, Complejo Asistencial Universitario de León, León, Spain

    Elvira Díez

  63. Rheumatology Department, Hospital Universitari MútuaTerrassa, Terrassa, Spain

    Georgina Salvador

  64. Rheumatology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain

    César Díaz

  65. Rheumatology Department, Hospital General La Mancha Centro, Ciudad Real, Spain

    Simón Sánchez

  66. Rheumatology Department, Complexo Hospitalario Universitario de Ourense, Ourense, Spain

    Alfredo Willisch Dominguez

  67. Rheumatology Department, Complejo Hospitalario Universitario de Pontevedra, Pontevedra, Spain

    José Antonio Mosquera

  68. Rheumatology Department, Hospital Clínic de Barcelona, Barcelona, Spain

    Julio Ramírez

  69. Rheumatology Department, Hospital Universitario 12 de Octubre, Madrid, Spain

    Esther Rodríguez Almaraz

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  1. Antonio Julià
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  2. Sergio H. Martínez-Mateu
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  3. Eugeni Domènech
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  4. Juan D. Cañete
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  7. Javier P. Gisbert
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  9. Esteban Daudén
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  11. Carolina Pérez
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  16. Mercedes Alpéri
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Consortia

for the IMID Consortium

  • Eduardo Fonseca
  • , Jesús Rodríguez
  • , Patricia Carreira
  • , Valle García
  • , José A. Pinto-Tasende
  • , Lluís Puig
  • , Elena Ricart
  • , Francisco Blanco
  • , Jordi Gratacós
  • , Ricardo Blanco
  • , Víctor Martínez Taboada
  • , Emilia Fernández
  • , Pablo Unamuno
  • , Isidoro González
  • , Fernando Gomollón García
  • , Raimon Sanmartí
  • , Ana Gutiérrez
  • , Àlex Olivé
  • , José Luís López Estebaranz
  • , Esther García-Planella
  • , Juan Carlos Torre-Alonso
  • , José Luis Andreu
  • , David Moreno Ramírez
  • , Benjamín Fernández
  • , Mª Ángeles Aguirre Zamorano
  • , Pablo de la Cueva
  • , Pilar Nos Mateu
  • , Paloma Vela
  • , Francisco Vanaclocha
  • , Héctor Coromines
  • , Santiago Muñoz
  • , Joan Miquel Nolla
  • , Enrique Herrera
  • , Carlos González
  • , José Luis Marenco de la Fuente
  • , Maribel Vera
  • , Alba Erra
  • , Daniel Roig
  • , Antonio Zea
  • , María Esteve Comas
  • , Carles Tomàs
  • , Pedro Zarco
  • , José María Pego
  • , Cristina Saro
  • , Antonio González
  • , Mercedes Freire
  • , Alicia García
  • , Elvira Díez
  • , Georgina Salvador
  • , César Díaz
  • , Simón Sánchez
  • , Alfredo Willisch Dominguez
  • , José Antonio Mosquera
  • , Julio Ramírez
  • , Esther Rodríguez Almaraz
  • , Núria Palau
  • , Raül Tortosa
  • , Mireia López
  • , Andrea Pluma
  •  & Adrià Aterido

Contributions

AJ designed the study, conceived, designed and analyzed data and wrote the manuscript; SH performed data curation and statistical analysis; ED, JDC, CF, JT, JPG, AFN, ED, MBA, CP, RQ, FJLL, JLSC, JLM, MA, CM, JJPV, FM, SC and MLL contributed to patient recruitment, clinical data collection and analysis and manuscript revision; AA contributed to genetic data analysis; SM designed the study, coordinated clinical data collection and analysis, and co-wrote the manuscript.

Corresponding authors

Correspondence to Antonio Julià or Sara Marsal.

Ethics declarations

Conflict of interest

The authors declare no competing interests.

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Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Members of the IMID Consortium are listed below Acknowledgements.

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Julià, A., Martínez-Mateu, S.H., Domènech, E. et al. Food groups associated with immune-mediated inflammatory diseases: a Mendelian randomization and disease severity study. Eur J Clin Nutr 75, 1368–1382 (2021). https://doi.org/10.1038/s41430-021-00913-6

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  • DOI: https://doi.org/10.1038/s41430-021-00913-6

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