Distinct transcriptional and metabolic profiles associated with empathy in Buddhist priests: a pilot study

Abstract

Background: Growing evidence suggests that spiritual/religious involvement may have beneficial effects on both psychological and physical functions. However, the biological basis for this relationship remains unclear. This study explored the role of spiritual/religious involvement across a wide range of biological markers, including transcripts and metabolites, associated with the psychological aspects of empathy in Buddhist priests.

Methods: Ten professional Buddhist priests and 10 age-matched non-priest controls were recruited. The participants provided peripheral blood samples for the analysis of gene expression and metabolic profiles. The participants also completed validated questionnaires measuring empathy, the Health-Promoting Lifestyle Profile-II (HPLP-II), and a brief-type self-administered diet history questionnaire (BDHQ).

Results: The microarray analyses revealed that the distinct transcripts in the Buddhist priests included up-regulated genes related to type I interferon (IFN) innate anti-viral responses (i.e., MX1, RSAD2, IFIT1, IFIT3, IFI27, IFI44L, and HERC5), and the genes C17orf97 (ligand of arginyltranseferase 1; ATE1), hemoglobin γA (HBG1), keratin-associated protein (KRTAP10-12), and sialic acid Ig-like lectin 14 (SIGLEC14) were down-regulated at baseline. The metabolomics analysis revealed that the metabolites, including 3-aminoisobutylic acid (BAIBA), choline, several essential amino acids (e.g., methionine, phenylalanine), and amino acid derivatives (e.g., 2-aminoadipic acid, asymmetric dimethyl-arginine (ADMA), symmetric dimethyl-arginine (SMDA)), were elevated in the Buddhist priests. By contrast, there was no significant difference of healthy lifestyle behaviors and daily nutrient intakes between the priests and the controls in this study. With regard to the psychological aspects, the Buddhist priests showed significantly higher empathy compared with the control. Spearman's rank correlation analysis showed that empathy aspects in the priests were significantly correlated with the certain transcripts and metabolites.

Conclusions: We performed in vivo phenotyping using transcriptomics, metabolomics, and psychological analyses and found an association between empathy and the phenotype of Buddhist priests in this pilot study. The up-regulation of the anti-viral type I IFN responsive genes and distinct metabolites in the plasma may represent systemic biological adaptations with a unique signature underlying spiritual/religious practices for Buddhists.

Fig. 1

The dot plots of the representative transcriptional markers identified in the priests. Dots represent subjects (circle, priests; square, controls), and line represents median. Eight genes were selected for validation by quantitative real-time PCR (qRT-PCR). qRT-PCR data are normalized to the housekeeping gene GAPDH. Differences of each transcript were compared using a Mann–Whitney U test, indicating P value and the effect size r. a MX1 (P = 0.0015, r = − 0.676), b IFI27 (P = 0.0115, r = − 0.558), c IFIT1 (P = 0.0433, r = − 0.456), d IFIT3 (P = 0.0115, r = − 0.558), e RSAD2 (P = 0.0068, r = − 0.592), f IFI44L (P = 0.0433, r = − 0.456), g HERC5 (P = 0.0029, r = − 0.642), and h C17orf97 (P = 0.0089, r = − 0.583). Statistical significance was defined as P < 0.05. Cohen’s guidelines for the effect sizes (r) for Mann–Whitney U test are that a large effect is 0.5, a medium effect is 0.3, and small effect is 0.1 [28]

Fig. 2

Representative four plasma metabolite markers identified in the priests. Dots represent subjects (circle, priests; square, controls), and line represents median. a Methionine in plasma of priests vs. the controls (P = 0.0002, r = − 0.761). b 3-Aminoisobutyric acid (BAIBA) in plasma of priests vs. the controls (P = 0.0015, r = − 0.676). c Phenylalanine in plasma of priests vs. the controls (P = 0.0029, r = − 0.642). d Choline in plasma of priests vs. the controls (P = 0.0052, r = − 0.608). Plasma level of each metabolite was shown as the relative area value calculated for metabolomics analysis by the Human Metabolome Technologies, Inc. The relative area value was defined as the relative concentration of each metabolite. Differences of each plasma metabolites were compared using a Mann–Whitney U test, indicating P value and the effect size r. Statistical significance was defined as P < 0.05. Cohen’s guidelines for the effect sizes (r) for Mann–Whitney U test are that a large effect is 0.5, a medium effect is 0.3, and small effect is 0.1 [28]

Fig. 3

Scatter plots of representative correlation between the molecular markers identified in the priests and empathy. Spearman’s rank correlation coefficients were calculated. Dots represent subjects (circle, priests; square, controls). a C17orf97 transcript vs. 3-aminoisobutyric acid (BAIBA) metabolite (ρ = − 0.636). b IFIT3 transcript vs. empathy aspect “Sharing negative emotions with others” (ρ = 0.603). c 3-Aminoisobutyric acid (BAIBA) metabolite vs. empathy aspect “Sharing positive emotions with others” (ρ = 0.700)