Chronotype and metabolites

 We have presented our ongoing research in a recently concluded World Ayurveda Conference. Here is the abstract of the work. The manuscript is in preparation.

Metabolomics analysis revealed chronotypes associated metabolic alterations in healthy human adults-a pilot clinical trial

Amey Shirolkar, Gitanjali Pawar, Shridhar Chougule, Manjusha Savardekar, Meenal Joshi, Anagha Ranade, Sharad Pawar, Prashant S. Duraphe*

Purpose: Chronobiology is the study of biological rhythms. It examines the effects of time on biological events and internal biological clocks. The phenotypic expression of internal clock is called chronotype. There are very few studies to associate biomolecules and pathways with specific chronotype. Metabolites are the most versatile biomolecules which reflects the current status of the metabolism. Hence, it would be clinically relevant to associate metabolite signature with the chronotype. We hypothesize that chronotypes and Ayurvedic prakriti types are associated and need further investigation.

Methods: Chronotypes of ten (10) healthy volunteers were analysed using validated ICER chronotype questionnaire which is a modified version of Munich Chronotype Questionnaire (MCTQ). Serum samples from these volunteers were utilized for isolating the metabolites and acquiring them in qualitative mode on a rapid resolution liquid chromatography - tandem mass spectrometry (RRLC-MS). The unbiased metabolomics profiling was explored to assess the signature metabolites and molecular pathways.

Results: The acquired metabolomics data was processed using statistical filters. Total 39 metabolites cleared the applied statistical filters. Partial Least Squared Discrimination analysis (PLS-DA) class prediction model yielded 93% accuracy in experimental groupings. T test (p<0.05), Fold change (FC>2.0) were also assessed and Purine, Glycerophospholipid and Thiamine metabolism were found to be the prominent metabolic pathways. Thiamine triphosphate, Deoxyuridine, Cyclic GMP, Epinephrine, Glycoholic Acid, Adenosine triphosphate, Phosphoadenosine phosphosulphate, lysophospholipid, phosphatidylethanolamines and phosphatidic acid were some of the significant marker metabolites found associated with morning and intermediate chronotypes. Adenosine triphosphate, glycoholic acid were down regulated when analysed in intermediate and morning chronotypes. While Phosphoadenosine phosphosulfate was found to be upregulated.

Conclusion: Omics analysis showed clear demarcation between chronotypes based on their metabolism and associated pathways hence it provides a potential tool to identify and characterize marker compounds for assigning chronotypes so as to incorporate chronotherapy in the disease diagnosis.