Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Neurological Sciences
Published in: Neurological Sciences 5/2020

01-05-2020 | Parkinson's Disease | Original Article

Quantitative metabolomics of saliva using proton NMR spectroscopy in patients with Parkinson’s disease and healthy controls

Authors: Sadhana Kumari, Vinay Goyal, S. Senthil Kumaran, S.N. Dwivedi, Achal Srivastava, N.R. Jagannathan

Published in: Neurological Sciences | Issue 5/2020

Login to get access

Abstract

Introduction

Parkinson’s disease (PD) is a multisystem disorder of unknown etiology, highlights a broad array of symptoms and pathological features influencing organs throughout the body. The metabolic profile of saliva in patients with PD may be influenced by malabsorption in the gastroenteric tract, neurodegeneration, and mitochondrial dysfunction. In the present study, we apply a powerful NMR metabolomics approach for biomarker identification in PD using saliva, a non-invasive bio-fluid.

Methods

Metabolic profiling of saliva were studied in patients with PD (n = 76) and healthy controls (HC, n = 37) were analyzed and differentiated PD from HC. A total of 40 metabolites including aromatic amino acids, short-chain fatty acids, branched chain amino acids, taurine, and N-acetylglutamate were identified. Spectral binned data and concentration of metabolites were estimated for analysis.

Results

Increased concentration of phenylalanine, tyrosine, histidine, glycine, acetoacetate, taurine, TMAO, GABA, N-acetylglutamate, acetoin, acetate, alanine, fucose, propionate, isoleucine, and valine were observed in PD as compared to HC. Further, subgroup analysis among early PD, advanced PD, and HC groups, revealed increased metabolite concentration in early PD group as compared to advanced PD and HC group.

Discussion

Analysis revealed potential biomarkers and their involvement in amino acid metabolism, energy metabolism, neurotransmitters metabolism, and microflora system. Patients with early PD exhibited higher metabolite concentration as compared to advanced PD group which might be associated with dopaminergic treatment.

Conclusion

The results of our data indicate that patients with PD might be characterized by metabolic imbalances like gut microflora system, energy metabolites, and neurotransmitters which may contribute to the PD pathogenesis.
Appendix
Available only for authorised users
Literature
1.
Licker V, Turck N, Kövari E, Burkhardt K, Côte M, Surini-Demiri M, Lobrinus JA, Sanchez JC, Burkhard PR (2014) Proteomic analysis of human substantia nigra identifies novel candidates involved in parkinson’s disease pathogenesis. Proteomics 14:784–794PubMedCrossRef
2.
3.
Hatano T, Saiki S, Okuzumi A, Mohney RP, Hattori N (2016) Identification of novel biomarkers for Parkinson’s disease by metabolomic technologies. J Neurol Neurosurg Psychiatry 87:295–301PubMedCrossRef
4.
5.
Poliquin PO, Chen J, Cloutier M, Trudeau LÉ, Jolicoeur M (2013) Metabolomics and in-silico analysis reveal critical energy deregulations in animal models of Parkinson’s disease. PLoS One 8:1–9CrossRef
6.
Tredici KD, Hawkes CH, Ghebremedhin E, Braak H (2010) Lewy pathology in the submandibular gland of individuals with incidental Lewy body disease and sporadic parkinson’s disease. Acta Neuropathol 119:703–713PubMedCrossRef
7.
Holsinger FC, Bui DT (2007) Anatomy, function, and evaluation of the salivary glands. Salivary Gland Disorders:1–16
8.
9.
Al-Nimer MSM et al (2014) Saliva α-synuclein and a high extinction coefficient protein: a novel approach in assessment biomarkers of Parkinson’s disease. N Am J Med Sci 6:633–637PubMedPubMedCentralCrossRef
10.
11.
Kang UJ, Taylor P, Naito A, Goldman JG (2018) Reply to: detection of alpha-synuclein in saliva: the importance of preanalytical assessment. Mov Disord 33:1031PubMedCrossRef
12.
Cao Z et al (2019) alpha-synuclein in salivary extracellular vesicles as a potential biomarker of Parkinson’s disease. Neurosci. Lett 696:114–120PubMedCrossRef
13.
Kumar V, Dwivedi DK, Jagannathan NR (2014) High-resolution NMR spectroscopy of human body fluids and tissues in relation to prostate cancer. NMR Biomed 27(80–89):2014
14.
Liang Q, Liu H, Zhang T, Jiang Y, Xing H, Zhang A (2015) Metabolomics-based screening of salivary biomarkers for early diagnosis of Alzheimer’s disease. RSC Adv 5:96074–96079CrossRef
15.
Figueira J, Jonsson P, Nordin Adolfsson A, Adolfsson R, Nyberg L, Öhman A (2016) NMR analysis of the human saliva metabolome distinguishes dementia patients from matched controls. Mol BioSyst 12:2562–2571PubMedCrossRef
16.
Benjamini Y, Hochberg Y (1995) Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc Ser B 57:289–300
17.
18.
Landrigan PJ, Sonawane B, Butler RN, Trasande L, Callan R, Droller D (2005) Early environmental origins of neurodegenerative disease in later life. Environ Health Perspect 113:1230–1233PubMedPubMedCentralCrossRef
19.
Farah R, Haraty H, Salame Z, Fares Y, Ojcius DM, Sadier NS (2018) Salivary biomarkers for the diagnosis and monitoring of neurological diseases. Biom J 41:63–87
20.
Bossy-Wetze E, Schwarzenbacher R, Lipton SA (2004) Molecular pathways to neurodegeneration. Nat Med 10:S2–S9CrossRef
21.
Figura M et al (2018) Serum amino acid profile in patients with Parkinson’s disease. PLoS 13:e0191670CrossRef
22.
23.
Dutkiewicz J, Szlufik S, Nieciecki M, Charzyńska I, Królicki L, Smektała P, Friedman A (2015) Small intestine dysfunction in Parkinson’s disease. J Neural Transm 122:1659–1661PubMedCrossRef
24.
Edwards LL, Quigley EMM, Pfeiffer RF (2012) Gastrointestinal dysfunction in Parkinson’s disease: frequency and pathophysiology. Neurology 42:726–732CrossRef
25.
Braham J, Sarova-Pinhas I, Crispin M, Golan R, Levin N, Szeinberg A (1969) Oral phenylalanine and tyrosine tolerance tests in Parkinsonian patients. Br Med J 2:552–555PubMedPubMedCentralCrossRef
26.
27.
Friedman JH, Goetz CC, Stebbins GT (1997) Psychotic symptoms in Parkinson’s disease. J Am Geriatr Soc 45:252–252PubMedCrossRef
28.
Franco-Iborra S, Vila M, Perier C (2018) Mitochondrial quality control in neurodegenerative diseases: focus on Parkinson’s disease and Huntington’s disease. Front Neurosci 12:342PubMedPubMedCentralCrossRef
29.
30.
Trupp M, Jonsson P, Ohrfelt A, Zetterberg H, Obudulu O, Malm L, Wuolikainen A, Linder J, Moritz T, Blennow K, Antti H, Forsgren L (2014) Metabolite and peptide levels in plasma and CSF differentiating healthy controls from patients with newly diagnosed Parkinson’s disease. J Park Dis 4:549–560
31.
Dunn L, Allen GF, Mamais A, Ling H, Li A, Duberley KE, Hargreaves IP, Pope S, Holton JL, Lees A, Heales SJ, Bandopadhyay R (2014) Dysregulation of glucose metabolism is an early event in sporadic Parkinson’s disease. Neurobiol Aging 35:1111–1115PubMedPubMedCentralCrossRef
32.
Kori M, Aydın B, Unal S, Arga KY, Kazan D (2016) Metabolic biomarkers and neurodegeneration: a pathway enrichment analysis of Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis. Omi A J Integr Biol 20:645–661CrossRef
33.
Fukao T, Mitchell G, Sass JO, Hori T, Orii K, Aoyama Y (2014) Ketone body metabolism and its defects. J Inherit Metab Dis 37:541–551PubMedCrossRef
34.
Flint HJ, Duncan SH, Scott KP, Louis P (2015) Links between diet, gut microbiota composition and gut metabolism. Proc Nutr Soc:7413–7422
35.
Mueller DM, Allenspach M, Othman A, Saely CH, Muendlein A, Vonbank A, Drexel H, von Eckardstein A (2015) Plasma levels of trimethylamine-N-oxide are confounded by impaired kidney function and poor metabolic control. Atherosclerosis 243:638–644PubMedCrossRef
36.
Uversky VN, Li J, Fink AL (2001) Pesticides directly accelerate the rate of α-synuclein fibril formation: a possible factor in Parkinson’s disease. FEBS Lett 500:105–108PubMedCrossRef
37.
Macfarlane S, Macfarlane GT (2003) Regulation of short-chain fatty acid production Proc. Nutr. Soc 62:67–72
38.
Cummings JH, Pomare EW, Branch WJ, Naylor CP, Macfarlane GT (1987) Short chain fatty acids in human large intestine, portal, hepatic and venous blood. Gut 28:1221–1227PubMedPubMedCentralCrossRef
39.
Morrison DJ, Preston T (2016) Formation of short chain fatty acids by the gut microbiota and their impact on human metabolism. Gut Microbes 7:189–200PubMedPubMedCentralCrossRef
40.
Marcobal A et al (2013) A metabolomic view of how the human gut microbiota impacts the host metabolome using humanized and gnotobiotic mice. ISME J 7:1933PubMedPubMedCentralCrossRef
41.
42.
Barbe AG, Bock N, Derman SHM, Felsch M, Timmermann L, Noack MJ (2017) Self-assessment of oral health, dental health care and oral health-related quality of life among Parkinson’s disease patients. Gerodontology 34:135–143PubMedCrossRef
43.
Babu GN, Gupta M, Paliwal VK, Singh S, Chatterji T, Roy R (2018) Serum metabolomics study in a group of Parkinson’s disease patients from northern India. Clin Chim Acta 480:214–219CrossRef
44.
Shannon K, Berghe PV (2018) The enteric nervous system in PD: gateway, by stander victim, or source of solutions. Cell Tissue Res 373:313–326PubMedCrossRef
Metadata
Title
Quantitative metabolomics of saliva using proton NMR spectroscopy in patients with Parkinson’s disease and healthy controls
Authors
Sadhana Kumari
Vinay Goyal
S. Senthil Kumaran
S.N. Dwivedi
Achal Srivastava
N.R. Jagannathan
Publication date
01-05-2020
Publisher
Springer International Publishing
Published in
Neurological Sciences / Issue 5/2020
Print ISSN: 1590-1874
Electronic ISSN: 1590-3478
DOI
https://doi.org/10.1007/s10072-019-04143-4

Other articles of this Issue 5/2020

Neurological Sciences 5/2020 Go to the issue

Original Article

Charcot-Marie-Tooth disease: experience from a large Italian tertiary neuromuscular center

Original Article

Biochemical parameters in determination of nutritional status in amyotrophic lateral sclerosis

Letter to the Editor

Is post-traumatic stress disorder a too underestimated factor in the early rehabilitation of cerebro-vascular events?

Letter to the Editor

Acute venous thrombosis of inferior cerebellar vein, case report

Original Article

Efficacy and safety of cerebrolysin in neurorecovery after moderate-severe traumatic brain injury: results from the CAPTAIN II trial

Letter to the Editor

A case of metabolic encephalopathy associated with euglycemic diabetic ketoacidosis