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In a recent study published in Nature medicine, A group of researchers evaluated the impact of vegan and ketogenic diets on the immune response and intestinal microbiota in humans.
Background
Nutrition significantly influences physiological processes, including immune regulation, and offers potential for dietary therapies in diseases such as cancer and chronic inflammation.
Research indicates that low-fat vegan or vegetarian diets may reduce inflammation and the risk of heart disease, while ketogenic diets may benefit certain types of epilepsy and reduce neuroinflammation. However, the precise effect of diet on human immunity is still unclear. Dietary choices affect not only nutrient intake but also the gut microbiome, which is crucial for health.
Although animal studies show a clear relationship between diet, microbiome and immunity, their impact on human immunity is less understood. More research is needed to fully understand the complex interplay between different diets and human immune responses, which will allow the development of personalized nutritional interventions to improve 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 between the ages of 18 and 50 who did not have metabolic or cardiovascular diseases. Participants, informed about the risks of the study, consented and were randomly assigned to first follow a vegan or ketogenic diet for two weeks and then switch to the alternative diet.
Meals were prepared following dietary guidelines and intake was monitored. Blood samples were collected from participants 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 extensive data sharing, which limited the availability of some data sets.
The study was powered to evaluate its primary and secondary outcomes, although the specific sample size was determined exploratory. Dietary interventions included meals designed to ensure compliance with the respective diets. The impact of these diets on several health markers was analyzed, but the researchers were not blinded to diet assignment.
Blood samples were processed for multiple analyses. Peripheral blood mononuclear cells (PBMCs) were isolated for flow cytometry and ribonucleic acid (RNA) analysis. Analysis of blood and plasma samples provided information on the effects of the diet on the immune system and metabolic pathways.
Study results
In the study, 20 participants underwent a crossover dietary intervention, consuming 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 non-starchy vegetables, but differed significantly in other components: the ketogenic diet included animal products, while the vegan diet incorporated plant-based foods. Differences in nutrient intake, particularly fatty acids and amino acids, were significant between diets.
The study evaluated the effects of these diets on participants’ immune cells, gene expression, protein composition, gut microbiota, and metabolic profiles. Various analyzes were performed, including flow cytometry, proteomics, microbiome sequencing, RNA sequencing, and metabolomics, although not all participants contributed to all data sets due to sample availability.
Flow cytometry revealed that both diets induced significant changes in immune cell composition, regardless of diet order. The ketogenic diet markedly increased the frequency of certain immune cells such as activated regulatory T cells and natural killer (NK) cells, while the vegan diet showed an increase in activated T helper and NK cells.
Whole blood RNA sequencing highlighted distinct gene expression patterns related 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. Furthermore, proteomic analysis suggested that the ketogenic diet may have broader effects on protein secretion and clearance, with sex-specific differences observed in response to the diets.
Microbiome analysis did not show a clear separation between the diets, but revealed significant changes in composition, especially after 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 dietary amino acid content reducing dependence on microbiome-derived amino acids.
Metabolomic analysis further demonstrated that diets had a significant impact on host metabolism, particularly lipid profiles. Correlation analyzes between data sets showed highly interconnected networks, driven mainly by factors related to amino acids, lipids and the immune system. This complex interaction highlighted the profound influence of diet on host physiology, encompassing immune responses, gut microbiota, and metabolic processes.