In a recent study published in Nature Medicine, a group of researchers evaluated the impact of vegan and ketogenic diets on immune response and gut microbiota in humans.
Nutrition significantly influences physiological processes, including immune regulation, offering potential for dietary therapies in diseases like cancer and chronic inflammation.
Research indicates that low-fat vegan or vegetarian diets can lower inflammation and heart disease risk, while ketogenic diets may benefit certain epilepsy types and reduce neuroinflammation. However, the precise effect of diet on human immunity is still unclear. Dietary choices affect not just nutrient intake but also the gut microbiome, which is crucial for health.
Although animal studies show a clear diet-microbiome-immunity relationship, its impact on human immunity is less understood. Further research is needed to fully understand the complex interplay between different diets and human immune responses, enabling the development of tailored nutritional interventions for improved health outcomes.
About the study
The present study was conducted between April 2019 and March 2020 at the National Institutes of Health (NIH) Clinical Center. It involved participants aged 18-50 who were free from metabolic and cardiovascular diseases. Participants, informed about study risks, gave consent and were randomly assigned to first follow either a vegan or ketogenic diet for two weeks, then switched to the alternate diet.
Meals were prepared following dietary guidelines and monitored for intake. Participants' blood samples were collected for various analyses, including flow cytometry, transcriptomics, proteomics, and metabolomics. The study also investigated the gut microbiome using collected stool samples. However, not all participants agreed to broad data sharing, limiting the availability of some data sets.
The study was statistically powered to assess its primary and secondary outcomes, although the specific sample size was determined exploratorily. Dietary interventions included designed meals to ensure adherence to the respective diets. The impact of these diets on various health markers was analyzed, but the researchers were not blinded to the diet allocation.
Blood samples were processed for multiple analyses. Peripheral blood mononuclear cells (PBMCs) were isolated for flow cytometry and ribonucleic acid (RNA) analysis. The analysis of blood and plasma samples provided insights into the dietary effects on the immune system and metabolic pathways.
In the study, 20 participants underwent a cross-over dietary intervention, consuming both a high-fat, low-carbohydrate ketogenic diet and a low-fat, high-carbohydrate vegan diet for two weeks each, in random order. Both diets shared a base of nonstarchy vegetables but differed significantly in other components: the ketogenic diet included animal-based products, while the vegan diet incorporated plant-based foods. Differences in nutrient intake, particularly in fatty acids and amino acids, were significant between the diets.
The study evaluated the effects of these diets on the participants' immune cells, gene expression, protein composition, gut microbiota, and metabolic profiles. Various analyses were performed, including flow cytometry, proteomics, microbiome sequencing, RNA sequencing, and metabolomics, though not all participants contributed to every data set due to sample availability.
Flow cytometry revealed that both diets induced significant changes in immune cell composition, irrespective of the diet order. The ketogenic diet notably increased the frequency of certain immune cells like activated regulatory T cells and natural killer (NK) cells, while the vegan diet showed an increase in activated T helper and NK cells.
RNA sequencing of whole blood highlighted distinct gene expression patterns linked to each diet. The ketogenic diet was associated with upregulated pathways related to adaptive immunity, such as T-cell activation, while the vegan diet showed different impacts. Additionally, proteomics analysis suggested that the ketogenic diet might have broader effects on protein secretion and clearance, with noted sex-specific differences in response to the diets.
Microbiome analysis did not show a clear separation between diets but revealed significant shifts in composition, especially following the ketogenic diet. This diet led to a notable decrease in microbial pathways related to amino acid and vitamin biosynthesis, possibly due to the high amino acid content in the diet reducing reliance on microbiome-derived amino acids.
Metabolomics analysis further demonstrated that diets significantly impacted host metabolism, particularly in lipid profiles. Correlation analyses across datasets showed highly interconnected networks, mainly driven by factors related to amino acids, lipids, and the immune system. This complex interplay highlighted the profound influence of diet on host physiology, encompassing immune responses, gut microbiota, and metabolic processes.