Research Paper Advance Articles
Exploring the role of acylated ghrelin and gut microbiome in delineating cognitive health in the elderly
- 1 Department of Biochemistry, All India Institute of Medical Sciences Bhubaneswar, Odisha 751019, India
- 2 Centre of Excellence for Clinical Microbiome and Research (CCMR), All India Institute of Medical Sciences Bhubaneswar, Odisha 751019, India
- 3 Department of Physiology, All India Institute of Medical Sciences Bhubaneswar, Odisha 751019, India
- 4 Department of Neurology, All India Institute of Medical Sciences Bhubaneswar, Odisha 751019, India
- 5 Adelaide Medical School, Faculty of Health and Medical Sciences, The University of Adelaide, Adelaide, SA 5000, Australia
Received: September 10, 2024 Accepted: January 30, 2025 Published: February 7, 2025
https://doi.org/10.18632/aging.206200How to Cite
Copyright: © 2025 Rout et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Introduction: With increased life expectancy, there is an increase in aging population and prevalence of dementia. Ghrelin is a key regulator of spatial memory and cognition. The gut microbiome may affect the circulating levels of unacylated ghrelin (UAG) and acylated ghrelin (AG). Thus, we explore the potential association of the gut microbiome, AG, and cognitive health in the aging dementia patient.
Methods: 40 dementia patients and 40 controls were recruited. Fecal Microbiome analysis using 16S rRNA sequencing was performed on 18 samples. A mixed-method approach was employed for robust interpretation.
Results: Dementia patients had an increased serum AG and AG/UAG ratio. With the increase in AG among dementia subjects, a significant decrease in species richness was observed. Bifidobacterium longum, Eubacterium biforme, Fecalibacterium prausnitzii, Lactobacillus ruminis, and Prevotella copri contributed to substantial differences in beta-diversity. Blautia obeum was associated with Mini-Mental State Examination (MMSE), and Fecalibacterium prausnitzii was associated with Montreal Cognitive Assessment (MoCA) Scale.
Discussion: This pilot study indicates a complex interaction between AG, gut microbiome, and cognitive scores. Increased AG corresponds to both dementia and gut dysbiosis, intricately interconnecting the gut-brain axis. The circulating AG and associated gut microbiome might be a putative biomarker for dementia.
Abbreviations
AAGR: Age associated Ghrelin Ratio; AG/UAG: Acylated Ghrelin/Unacylated Ghrelin ratio; AG: Acylated Ghrelin; AIIMS: All India Institute of Medical Science; AMPA: α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid; AUC: Area under the curve; BDNF: Brain derived neurotropic factor; BMI: Body mass index; BNR: Bodepudi Narasimha Rao; BR: Balamurugan Ramadass; cAMP: CREB-cyclic Adenosine monophosphate-cAMP response element binding protein; CCMR: Centre of Excellence for Clinical Microbiome and Research; CFA: Confirmatory Factor Analysis; DB: Debapriya Bandhyopadhyay; ELISA: Enzyme Linked Immuno Sorbet Assay; F/B: Firmecutis/Bacteroidetes; GABA: Gamma amino butyric acid; GADL: General Activities of Disease Living Scale; GHSR: growth hormone secretagogue receptor; GOAT: ghrelin O-acyltransferase; GV: Giriprasad Venugopal; HADS-A: Hospital Anxiety and Depression Scale-Anxiety; HADS-D: Hospital Anxiety and Depression Scale-Depression; lv1: latent variable 1; lv2: latent variable 2; MMSE: Mini Mental State Examination; MoCA: Montreal Cognitive Assessment; MoHFW: Ministry of Health and Family Welfare; OPD: Out Patient Department; OTU: Operational Taxonomic Unit; PCoA: Principal coordinate analysis; PDD: Parkinson’s disease dementia; PD: Parkinson’s disease; QC: Quality Check; RD: Rishikesh Dash; ROC: Receiver operating characteristic; rRNA: ribosomal Ribonucleic acid; SCFA: short chain fatty acid; SD: Standard Deviation; SEM: Structural Equation Model; SHAP: Shapley Additive exPlanations; SIMPER: Similarity Percentage; SKB: Sanjeev Kumar Bhoi; SR: Sudeshna Rout; UAG: Unacylated Ghrelin; VS: Varsha Satish.