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Large-scale genomic study reveals robust activation of the immune system following advanced Inner Engineering meditation retreat.

ABSTRACT: The positive impact of meditation on human well-being is well documented, yet its molecular mechanisms are incompletely understood. We applied a comprehensive systems biology approach starting with whole-blood gene expression profiling combined with multilevel bioinformatic analyses to characterize the coexpression, transcriptional, and protein-protein interaction networks to identify a meditation-specific core network after an advanced 8-d Inner Engineering retreat program. We found the response to oxidative stress, detoxification, and cell cycle regulation pathways were down-regulated after meditation. Strikingly, 220 genes directly associated with immune response, including 68 genes related to interferon signaling, were up-regulated, with no significant expression changes in the inflammatory genes. This robust meditation-specific immune response network is significantly dysregulated in multiple sclerosis and severe COVID-19 patients. The work provides a foundation for understanding the effect of meditation and suggests that meditation as a behavioral intervention can voluntarily and nonpharmacologically improve the immune response for treating various conditions associated with excessive or persistent inflammation with a dampened immune system profile.

SUBMITTER: Chandran V

PROVIDER: S-EPMC8713789 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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Large-scale genomic study reveals robust activation of the immune system following advanced Inner Engineering meditation retreat.

Chandran Vijayendran V Bermúdez Mei-Ling ML Koka Mert M Chandran Brindha B Pawale Dhanashri D Vishnubhotla Ramana R Alankar Suresh S Maturi Raj R Subramaniam Balachundhar B Sadhasivam Senthilkumar S

Proceedings of the National Academy of Sciences of the United States of America 20211201 51

The positive impact of meditation on human well-being is well documented, yet its molecular mechanisms are incompletely understood. We applied a comprehensive systems biology approach starting with whole-blood gene expression profiling combined with multilevel bioinformatic analyses to characterize the coexpression, transcriptional, and protein-protein interaction networks to identify a meditation-specific core network after an advanced 8-d Inner Engineering retreat program. We found the respons ...[more]

PMID: 34907015

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Project description:Purpose: The goal of this study was to characterized the transcriptome profiles of whole-blood cells from 388 specimens obtained from 106 individuals before and after the meditation retreat at four-time points (T1–T4) by RNA sequencing (RNA-Seq). T1 samples were collected 5-8 weeks before the retreat, T2 samples were collected on the day of retreat before starting the meditation method, T3 samples were collected immediately after the retreat, and T4 samples were collected three months after the retreat. Methods: The human blood samples were collected into PAXgene Blood RNA Tubes and stored at -80°C freezer. Before RNA extraction the samples were removed from -80°C and incubated overnight at room temperature. The samples were randomized before RNA extraction to eliminate any time point or age or sex or batch effect. Manufacturer’s protocol of manual purification of total RNA from human whole blood was followed (Qiagen, cat #762164). RNA was reverse transcribed to complementary DNA (Lexogen QuantSeq 3′ FWD), and sequenced on a HiSeq 4000 instrument (Illumina). Results: We applied a comprehensive systems biology approach starting with whole blood gene expression profiling combined with multi-level bioinformatic analyses to characterize the co-expression, transcriptional, and protein-protein interaction networks to identify meditation-specific core network after an advanced eight-day Inner Engineering retreat program. We found the response to oxidative stress, detoxification, and cell cycle regulation pathways were downregulated after meditation. Strikingly, 220 genes directly associated with immune response, including 68 genes related to interferon (IFN) signaling were upregulated, with no significant expression changes in the inflammatory genes. This robust meditation-specific immune response network is significantly dysregulated in multiple sclerosis and severe COVID-19 patients. Conclusions: The present proof-of-principle study demonstrates that the immune system can be voluntarily influenced by non-pharmaceutical interventions like yoga and meditation. This suggests that meditation as a behavioral intervention could have important implications for treating various conditions associated with excessive or persistent inflammation with a dampened immune system profile.

Project description:Under the current policy decision making paradigm we make or evaluate a policy decision by intervening different socio-economic parameters and analyzing the impact of those interventions. This process involves identifying the causal relation between interventions and outcomes. Matching method is one of the popular techniques to identify such causal relations. However, in one-to-one matching, when a treatment or control unit has multiple pair assignment options with similar match quality, different matching algorithms often assign different pairs. Since all the matching algorithms assign pairs without considering the outcomes, it is possible that with the same data and same hypothesis, different experimenters can reach different conclusions creating an uncertainty in policy decision making. This problem becomes more prominent in the case of large-scale observational studies as there are more pair assignment options. Recently, a robust approach has been proposed to tackle the uncertainty that uses an integer programming model to explore all possible assignments. Though the proposed integer programming model is very efficient in making robust causal inference, it is not scalable to big data observational studies. With the current approach, an observational study with 50,000 samples will generate hundreds of thousands binary variables. Solving such integer programming problem is computationally expensive and becomes even worse with the increase of sample size. In this work, we consider causal inference testing with binary outcomes and propose computationally efficient algorithms that are adaptable for large-scale observational studies. By leveraging the structure of the optimization model, we propose a robustness condition that further reduces the computational burden. We validate the efficiency of the proposed algorithms by testing the causal relation between the Medicare Hospital Readmission Reduction Program (HRRP) and non-index readmissions (i.e., readmission to a hospital that is different from the hospital that discharged the patient) from the State of California Patient Discharge Database from 2010 to 2014. Our result shows that HRRP has a causal relation with the increase in non-index readmissions. The proposed algorithms proved to be highly scalable in testing causal relations from large-scale observational studies.

Project description:Thirty-eight individuals (mean age: 34.8 years old) participating in a 3-month yoga and meditation retreat were assessed before and after the intervention for psychometric measures, brain derived neurotrophic factor (BDNF), circadian salivary cortisol levels, and pro- and anti-inflammatory cytokines. Participation in the retreat was found to be associated with decreases in self-reported anxiety and depression as well as increases in mindfulness. As hypothesized, increases in the plasma levels of BDNF and increases in the magnitude of the cortisol awakening response (CAR) were also observed. The normalized change in BDNF levels was inversely correlated with BSI-18 anxiety scores at both the pre-retreat (r = 0.40, p < 0.05) and post-retreat (r = 0.52, p < 0.005) such that those with greater anxiety scores tended to exhibit smaller pre- to post-retreat increases in plasma BDNF levels. In line with a hypothesized decrease in inflammatory processes resulting from the yoga and meditation practices, we found that the plasma level of the anti-inflammatory cytokine Interleukin-10 was increased and the pro-inflammatory cytokine Interleukin-12 was reduced after the retreat. Contrary to our initial hypotheses, plasma levels of other pro-inflammatory cytokines, including Interferon Gamma (IFN-γ), Tumor Necrosis Factor (TNF-α), Interleukin-1β (IL-1β), Interleukin-6 (IL-6), and Interleukin-8 (IL-8) were increased after the retreat. Given evidence from previous studies of the positive effects of meditative practices on mental fitness, autonomic homeostasis and inflammatory status, we hypothesize that these findings are related to the meditative practices throughout the retreat; however, some of the observed changes may also be related to other aspects of the retreat such as physical exercise-related components of the yoga practice and diet. We hypothesize that the patterns of change observed here reflect mind-body integration and well-being. The increased BDNF levels observed is a potential mediator between meditative practices and brain health, the increased CAR is likely a reflection of increased dynamic physiological arousal, and the relationship of the dual enhancement of pro- and anti-inflammatory cytokine changes to healthy immunologic functioning is discussed.

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Large-scale genomic study reveals robust activation of the immune system following advanced Inner Engineering meditation retreat.

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Large-scale genomic study reveals robust activation of the immune system following advanced Inner Engineering meditation retreat.

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