Study explores the effects of different diets on plasma proteins

By Neha MathurAug 22 2023Reviewed by Sophia Coveney

In a recent article posted to the medRxiv* server, researchers investigated the relationship between diet and the proteome, defined as the set of circulating proteins at a given time in a type of cell, tissue, or the whole organism. 

*Important notice: medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

A better understanding of this association could help gain insights into the effects of different diets on the proteome, which plays a crucial role in several biological processes, such as cell and tissue growth, cellular signaling and transport functions, and structural integrity. Further, these insights could help identify early-stage biomarkers for future diseases to inform dietary guidelines and recommendations for improving public health. 

Background

Diet is an exogenous source of nine essential amino acids the human body cannot synthesize but are needed for synthesizing multiple proteins involved in many critical biological processes. An individual's diet could alter the expression of many of these proteins and their underlying pathways.

Previous studies have examined the effects of dietary habits on circulating levels of amino acids. However, there is a lack of data on how plant-based diets affect the proteome.

About the study

In the present study, researchers used data from 40-69-year-old middle-aged people from the United Kingdom (UK) Biobank recruited between 2006-2010. They invited people within ~25 km of one of 22 National Health Service (NHS) assessment centers in England, Wales, and Scotland to join this study.

Those who provided consent attended a baseline visit, where they filled out a questionnaire enquiring about their diet, alcohol consumption, smoking status, physical activity levels, socio-demographic characteristics, and medical history. 

They self-reported their ethnicities and dietary intake of red and processed meat, fish, dairy, eggs, and poultry.

Based on this information, the team included White and British Indian people in this study. The British Indian population had 25% vegetarians compared to <2% in the general population; thus, their inclusion allowed valid comparisons by diet groups.

Further, they classified white British participants into six diet groups and British Indian participants into two diet groups. There were 23,116 regular meat eaters, 23,323 low meat eaters, 484 poultry eaters, 1,074 fish eaters, 722 vegetarians, and 54 vegans in six diet groups of the white British participants, and 390 meat eaters and 163 vegetarians in two diet groups of the British Indian participants.

Trained personnel collected non-fasting blood samples from 49,326 participants for proteomic profiling; 48,773 were white British, and 553 were British Indian. The researchers used the Olink Proximity Extension Assay for proteomic profiling of all the collected samples. It measured the relative abundance of 1,472 protein analytes, encompassing 1,463 plasma circulating proteins, and expressed it as normalized protein expression (NPX) values.

The team used a multivariable-adjusted linear regression model to estimate differences in protein concentrations by diet group, with correction for multiple testing. They used 'regular meat eaters' and 'meat eaters' as reference groups for the white British and British Indian participants. 

Furthermore, the team conducted a principal component analysis to account for high correlations between the circulating proteins and multiple testing in the complete proteins dataset. They also assessed overall heterogeneity between diet groups in each ethnicity and pairwise comparisons of all diet groups and the reference groups using Wald tests. 

Lastly, they performed sensitivity analyses for the top 10 proteins in each pairwise comparison against the reference group to evaluate the influence of key study covariates on the observed associations. These were body mass index, smoking, and alcohol consumption, which are important determinants of health outcomes. 

Results

The authors noted substantial differences in circulating protein levels across all diet groups, especially in proteins expressed in the digestive system, suggesting their relation to future disease risks for people with different dietary preferences.

Among the six diet groups of white British participants, 683 plasma proteins varied significantly, including 535 plasma proteins in one or more pairwise comparisons between regular meat eaters and at least one of the other diet groups. In the two British Indian diet groups, only one circulating plasma protein showed a significant difference. 

These findings suggested that the impact of the dietary habits of white British participants was more significant on the plasma proteome than on British Indians. However, since this study covered a small sample of British Indians, further research with a larger sample size is needed to confirm these findings.

Notably, the magnitudes of differences in many proteins were generally directionally consistent and showed a gradient effect across the diet groups.

Circulating proteins, such as folate receptor 1 (FOLR1), a protein associated with nutritional status, and desmogleins 2 (DSG2), showed higher concentrations in non-meat eaters, especially vegans, than regular meat eaters. Other proteins with higher expression in non-meat eaters were fibroblast growth factor 21 (FGF21), guanylate cyclase activator 2A (GUCA2A), and insulin-like growth factor binding protein 2 (IGFBP2).

The authors also noted lower hepatitis A virus cellular receptor 1 (HAVcr-1), recognized as an early diagnostic marker of kidney disease, in non-meat eaters, indicating the adverse effects of diets high in animal protein on kidney health. 

Furthermore, the authors observed varying expression of 27 proteins in the brain and seven proteins in the lung across all diet groups, suggesting the need for further research on the potential effects of different dietary patterns on these organs.

Conclusions

The observed variations in the plasma proteome of different diet groups of this study suggested physiological differences, including the gastrointestinal tract and kidney function of meat and non-meat eaters. Future studies should further investigate the observed impact of plant-based diets on the plasma proteome and their varying effects on disease risks.

*Important notice: medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.