The plasma proteome of plant-based diets: analyses of 1463 proteins in 50,000 people

Background and objectives Circulating proteins are integral to many biological processes. We aimed to assess differences in the plasma proteome between people of different dietary groups defined by degree of animal food consumption. Methods The UK Biobank recruited middle-aged adults (mostly 40 to 69 years) throughout the UK between 2006-2010. Relative concentrations of 1463 plasma proteins were quantified using the Olink Proximity Extension Assay on blood samples from 49,326 participants, who were also asked to report their ethnicity and consumption of red and processed meat, poultry, fish, dairy and eggs. We defined six diet groups among the white British participants (23,116 regular meat eaters, 23,323 low meat eaters, 484 poultry eaters, 1074 fish eaters, 722 vegetarians, and 54 vegans), and two diet groups among the British Indians (390 meat eaters and 163 vegetarians). We used multivariable-adjusted linear regressions to assess differences in protein concentrations between diet groups, with correction for multiple testing. Results We observed significant differences in many plasma proteins by diet group (683 proteins in white British participants, 1 in British Indians), in particular many proteins that are majority expressed in the digestive system. Of the biggest differences, compared with regular meat eaters, the non-meat eaters had significantly higher FGF21 (e.g. +0.40 SD in vegetarians), GUCA2A (+0.33), FOLR1 (+0.32), IGFBP2 (+0.31) and DSG2 (+0.30); all groups except the vegans had lower HAVCR1 (−0.38 in vegetarians). The observed differences were generally similar in direction in both ethnicities. Discussion In this first comprehensive assessment of plasma proteins by diet group, we identified many differences in proteins between groups defined by animal food consumption; this variation in protein levels suggests differences in various biological activities, including gastrointestinal tract and kidney function, which may relate to differences in future disease risk. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement The work is supported by the UK Medical Research Council (MR/M012190/1), Wellcome Trust Our Planet Our Health (Livestock, Environment and People, LEAP 205212/Z/16/Z) and Cancer Research UK (C8221/A29017 and C8221/A29186). TYNT is support by a Nuffield Departmental of Population Health Fellowship. The funders had no role in study design, data collection, analysis, decision to publish, or preparation of the manuscript. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Permission for access to patient records for recruitment was approved by the Patient Information Advisory Group (now the National Information Governance Board for Health and Social Care) in England and Wales and the Community Health Index Advisory Group in Scotland, and all participants gave informed consent to participate using a signature capture device at the baseline visit. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes UK Biobank is an open access resource. Bona fide researchers can apply to use the UK Biobank dataset by registering and applying at