Implications of Butyrate Signaling Pathways on the Motor Symptomatology of Parkinson’s Disease and Neuroprotective Effects—Therapeutic Approaches: A Systematic Review
Abstract
:1. Introduction
1.1. Parkinson Disease
1.2. Butyrate Signaling Pathways in PD
2. Results
2.1. Data Extraction
- Population (description).
- Model PD-induced.
- Intervention (dose administered, time, and frequency).
- Methodology and results obtained after the intervention.
Ref. | Population and Model | Intervention | Methodology and Results |
---|---|---|---|
[49] | PD male Sprague–Dawley rats induced by 6-OHDA (12 μg in 0.1% ascorbic acid) | The sham-injured animals were administered an ascorbic acid/acidic saline solution (4 mL). Prior to induction of injury, MPEP or L-AP4 (2 nmol in 4 mL) were administered intraneural, alone or in combination. The controls received the vehicle alone, and the treatment was continued for 7 days | Sham and control groups were observed |
Significant attenuation of nigral TH-IR cell loss with either MPEP or L-AP4 alone | |||
Greater preservation of nigral TH-IR cells with coadministration | |||
Significant attenuation of DA and metabolite depletion with either MPEP or L-AP4 alone | |||
[50] | PD C57BL/6 mice (4–6 months old) induced by MPTP (20 mg/kg) | The control mice were administered water containing equimolar concentrations of sodium chloride, PB (phenylbutyrate), and NaB for a period of 14 days. The PB and NaB groups were administered these substances in water at concentrations of 500, 1000, 1500, and 2000 mg/L | The control group, PB group, and NaB group were observed |
Notable elevation in DJ-1 levels | |||
No change in α-synuclein concentrations, suggesting a selective increase in DJ-1 expression | |||
PB treatment resulted in a significantly higher number of TH-positive dopaminergic neurons in the substantia nigra | |||
[51] | PD adult male Wistar rats induced by 6-OHDA (8 μg in 1 μL in 0.2% ascorbic acid) | A single stereotaxic dose of 1 μL of 5-HT (10 μg/μL), GABA (10 μg/μL), and BMC (106 cells/μL) in combinations was infused (day 18) into the right SNpc (0.2 μL/min) | Control, 6-OHDA, (6-OHDA + BMC), (6-OHDA + 5-HT + BMC), (6-OHDA + GABA + BMC), and (6-OHDA + 5-HT + GABA + BMC) were observed |
The combinational treatment of 5-HT, GABA, and BMC resulted in a significant attenuation of TBAR levels | |||
Significant reversal of SOD, CAT, and GPx enzyme activities to near-control levels | |||
[52] | PD male C57BL/6 mice (6–8 weeks old) induced by MPTP (30 mg/kg) | Sham group (intraperitoneal injection of normal saline). NaB (200 or 600 mg/kg) gavage-treated groups (3 weeks) | Sham group, MPTP group, MPTP + NaB group (200 mg/kg), and MPTP + NaB group (600 mg/kg) were observed |
NaB relieved MPTP-triggered motor dysfunction and dopaminergic neuronal death in mice | |||
Mitigated MPP+-induced apoptosis | |||
NaB alleviated MPP+-stimulated oxidative stress and inflammatory responses in PC12 cells | |||
[53] | PD male C57BL mice (8–10-weeks-old) induced by MPTP (18 mg/kg) | Vehicle, DβHB (1.6, 0.8, or 0.4 mmol/kg/day in saline, pH 7.4), and LβHB (1.6 mmol/kg/day in saline, pH 7.4) were administered subcutaneously (1 μL/h). 3-NP (15 mg/kg in 0.1 M PBS adjusted to pH 7.4) was administered intraperitoneally 2 h before implantation on day 1. | The vehicle group, DβHB group, LβHB group, and DβHB plus 3-nitropropionic acid (3-NP) groups were observed |
DβHB has shown significant improvement in motor function | |||
Complete restoration of MPP+-inhibited oxygen consumption is only partially possible in the presence of rotenone | |||
No antioxidant effects | |||
Enhanced ATP production | |||
[54] | PD male C57BL/B6 mice induced by MPTP (30 mg/kg) | A solution of NaB diluted in normal saline (200 mg/kg) was administered intragastrically for 3 weeks after a 7-day treatment with MPTP. Groups (1) and (2) received an equal volume of saline | Control, PD model, and NaB treatment groups were observed |
NaB treatment has shown an effective alleviation of motor deficits and an improved state of despair in PD model mice | |||
Significant elevation in TH expression | |||
Statistically higher number of TH-positive neurons in the substantia nigra compared to the PD group | |||
[55] | PD male C57BL/6 mice (6–8 weeks old) induced by Mn (30 mg/kg) | An intraperitoneal injection of VPA (200 mg/kg), NaB (1200 mg/kg), or saline (NaCl, 0.9%; control) was administered for 21 days. VPA and NaB were diluted in saline (0.9%). After a 30 min period, the Mn + VPA, Mn+NaB, and Mn groups received 2 μL of MnCl2 (30 mg/kg) | The control group, VPA group, Mn group, Mn plus VPA group, NaB group, and Mn plus NaB group were observed |
Significant reversal of Mn-induced motor deficits by both VPA and NaB | |||
No change in rotarod performance with VPA or NaB alone compared to control | |||
NaB co-treatment with Mn attenuated Mn-decreased GLT-1 mRNA levels in the cerebral cortex and cerebellum, similar to VPA | |||
NaB reversed the Mn-induced reduction of GLAST mRNA levels in the cortex | |||
[56] | PD male C57BL/6J mice (7-weeks-old) induced by MPTP (15 mg/kg) | The probiotic group consumed approximately 2 × 106 CFU of microorganisms/day for 30 days (Lactobacillus rhamnosus GG, Bifidobacterium animalis lactis, and Lactobacillus acidophilus; vehicle (lactose+maltodextrin) | First, mice were divided into vehicle- and probiotic-treated groups, which were then subdivided into saline- and MPTP-administered groups |
Probiotics have shown a reduction in motor errors induced by MPTP | |||
Significant prevention of dopaminergic nerve terminal loss in the striatum | |||
Attenuation of MPTP-mediated astrocyte activation | |||
Significant prevention of BDNF and GDNF suppression in substantia nigra tissue | |||
[57] | PD male C57BL/6J mice (8-week-old) induced by MPTP (15 mg/kg) | The control group received a daily oral gavage of distilled water (4 weeks) followed by a saline injection. The PD group received distilled water by oral gavage (4 weeks), followed by an injection of MPTP. The polymannuronic acid-treated group received polymannuronic acid (30 mg/kg) by oral gavage (4 weeks) | Normal, model, and PM groups were observed |
PM treatment has shown a notable improvement in motor functions | |||
Substantial elevation of HVA, 5-HT, and 5-HIAA levels in the striatum | |||
Significant increase in fecal concentrations of total SCFAs and specific SCFAs (acetic acid, propionic acid, and butyric acid), contributing to neuroprotective effects | |||
[58] | PD male C57BL/6J mice (8-weeks-old) induced by MPTP (30 mg/kg) | PD mouse group (0.2 g/kg or 2.0 g/kg sodium acetate-NaA-L or NaA–H), PD mouse group (0.2 g/kg or 2.0 g/kg of sodium propionate-NaP-L or NaP-H), group of PD mice (0.2 g/kg or 2.0 g/kg of sodium butyrate-NaB-L or NaB-H), and group of PD mice (0.1 g/kg levodopa as positive control group (L-dopa) | (Con), (PD), (NaA-L or NaA–H), (NaP-L or NaP-H), (NaB-L or NaB-H), and (L-dopa) groups were observed |
Only NaB treatment has shown a notable enhancement in motor functions | |||
NaB was identified as the most efficacious in mitigating brain damage | |||
Discernible increase in dopaminergic positive neuronal cells and reduction in α-synuclein accumulation | |||
[59] | PD male Swiss CD1 mice (10-week-old) induced by 6-OHDA (4 µg/2 µL) | Sham control group (intrastriatal injection of vehicle); 6-OHDA, 6-OHDA+NaB (6-OHDA and NaB treated); 6-OHDA + CFX, (CFX for 5 days and intrastriatal injection of 6-OHDA); 6-OHDA + CFX + NaB (CFX, intrastriatal injection of 6-OHDA and NaB treatment); and CFX (antibiotic solely for 5 days) | Sham control mice, 6-OHDA, 6-OHDA + NaB, 6-OHDA + CFX, 6-OHDA + CFX + NaB, and CFX groups were observed |
NaB (in 6-OHDA and dual-insulted mice) showed improvement in motor coordination by day 7 | |||
Increased Bcl-2 immunoreactivity and decreased Bax expression in the striata | |||
Reversal of the Bcl-2/Bax ratio in untreated 6-OHDA and 6-OHDA + CFX mice | |||
Limited systemic inflammation and endotoxemia in 6-OHDA + CFX mice | |||
[60] | PD male C57BL/6J mice (7-weeks-old) induced by MPTP (20 mg/kg) | In the second and third weeks, in the MPTP + NaB group and the MPTP + MMF group (NaB: 600 mg/kg/day) and (MMF: 100 mg/kg/day), PBS (10 mL/kg/day) was administered to both the control group and the MPTP + vehicle group. | The control group, MPTP + vehicle group, MPTP + NaB group, and MPTP + MMF group were observed |
NaB and MMF showed alleviated coordination impairment compared to the control group | |||
Reduced loss of TH-positive dopaminergic neurons in the SNpc | |||
Substantially reduced serum levels of IL-6 and TNF-α | |||
[61] | PD male C57BL/6J mice (7-weeks-old) induced by MPTP (30 mg/kg) | MPTP and MPTP + NaB groups (30 mg/kg MPTP intraperitoneally) for 7 days. Control group (normal saline); NaB or saline intragastrically (14 days) after a 2 h interval after the 21-day MPTP injection period | The control group, MPTP group, and MPTP + NaB group were observed |
NaB treatment has shown significant improvement in motor functions | |||
A marked increase in DA and 5-HT levels in the striatum compared to MPTP mice | |||
Reduction in GFAP expression and suppression of glial cell activation, leading to reduced neuroinflammation | |||
[62] | PD male C57BL/6 mice (8-week-old) induced by MPTP (30 mg/kg) | Group C (saline gelatin—14 days); Group M (saline gelatin—7 days); Group L (intraperitoneal injection of 0.4 mg/kg liraglutide—7 days); Group CB (108 CFU. of C. butyricum by gavage in saline containing 0.01% gelatin—7 days); Group CBG (same dose and duration) | G, C, M, L, CB, and CBG groups were observed |
Significant enhancement of locomotor capacity in the M group C. butyricum-GLP-1 or liraglutide treatment | |||
No statistical difference between C. butyricum-GLP-1 and liraglutide treatments |
2.2. Quality of Included Studies
2.3. Neuroprotective Effects of Butyrate in PD
2.4. Efficacy of Butyrate Regulation in Improving Motor Symptoms in PD
3. Discussion
3.1. Limitations and Future Research
3.2. Practical Applications
4. Methods
4.1. Protocol and Registration
4.2. Literature Search
4.3. Search Strategy
4.4. Inclusion Criteria
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Dorsey, E.R.; Sherer, T.; Okun, M.S.; Bloem, B.R. The Emerging Evidence of the Parkinson Pandemic. J. Parkinson’s Dis. 2018, 8, S3–S8. [Google Scholar] [CrossRef] [PubMed]
- Huang, M.; Bargues-Carot, A.; Riaz, Z.; Wickham, H.; Zenitsky, G.; Jin, H.; Anantharam, V.; Kanthasamy, A.; Kanthasamy, A.G. Impact of Environmental Risk Factors on Mitochondrial Dysfunction, Neuroinflammation, Protein Misfolding, and Oxidative Stress in the Etiopathogenesis of Parkinson’s Disease. Int. J. Mol. Sci. 2022, 23, 10808. [Google Scholar] [CrossRef]
- Meoni, S.; Cury, R.G.; Moro, E. New players in basal ganglia dysfunction in Parkinson’s disease. In Progress in Brain Research; Elsevier: Amsterdam, The Netherlands, 2020; pp. 307–327. [Google Scholar]
- Shahnawaz, M.; Mukherjee, A.; Pritzkow, S.; Mendez, N.; Rabadia, P.; Liu, X.; Hu, B.; Schmeichel, A.; Singer, W.; Wu, G.; et al. Discriminating α-synuclein strains in Parkinson’s disease and multiple system atrophy. Nature 2020, 578, 273–277. [Google Scholar] [CrossRef] [PubMed]
- Jankovic, J.; Tan, E.K. Parkinson’s disease: Etiopathogenesis and treatment. J. Neurol. Neurosurg. Psychiatry 2020, 91, 795–808. [Google Scholar] [CrossRef]
- Ratan, Y.; Rajput, A.; Pareek, A.; Pareek, A.; Jain, V.; Sonia, S.; Farooqui, Z.; Kaur, R.; Singh, G. Advancements in Genetic and Biochemical Insights: Unraveling the Etiopathogenesis of Neurodegeneration in Parkinson’s Disease. Biomolecules 2024, 14, 73. [Google Scholar] [CrossRef]
- Blauwendraat, C.; Nalls, M.A.; Singleton, A.B. The genetic architecture of Parkinson’s disease. Lancet Neurol. 2020, 19, 170–178. [Google Scholar] [CrossRef] [PubMed]
- Sosero, Y.L.; Gan-Or, Z. LRRK2 and Parkinson’s disease: From genetics to targeted therapy. Ann. Clin. Transl. Neurol. 2023, 10, 850–864. [Google Scholar] [CrossRef] [PubMed]
- Gialluisi, A.; Reccia, M.G.; Modugno, N.; Nutile, T.; Lombardi, A.; Di Giovannantonio, L.G.; Pietracupa, S.; Ruggiero, D.; Scala, S.; Gambardella, S.; et al. Identification of sixteen novel candidate genes for late onset Parkinson’s disease. Mol. Neurodegener. 2021, 16, 35. [Google Scholar] [CrossRef] [PubMed]
- Li, Y.; Xia, Y.; Yin, S.; Wan, F.; Hu, J.; Kou, L.; Sun, Y.; Wu, J.; Zhou, Q.; Huang, J.; et al. Targeting Microglial α-Synuclein/TLRs/NF-kappaB/NLRP3 Inflammasome Axis in Parkinson’s Disease. Front. Immunol. 2021, 12, 719807. [Google Scholar] [CrossRef]
- Ho, M.S. Microglia in Parkinson’s Disease. In Neuroglia in Neurodegenerative Diseases; Springer: Singapore, 2019; pp. 335–353. [Google Scholar]
- Mehra, S.; Sahay, S.; Maji, S.K. α-Synuclein misfolding and aggregation: Implications in Parkinson’s disease pathogenesis. Biochim. Biophys. Acta (BBA) Proteins Proteom. 2019, 1867, 890–908. [Google Scholar] [CrossRef] [PubMed]
- Chen, R.; Gu, X.; Wang, X. α-Synuclein in Parkinson’s disease and advances in detection. Clin. Chim. Acta 2022, 529, 76–86. [Google Scholar] [CrossRef] [PubMed]
- Vidović, M.; Rikalovic, M.G. Alpha-Synuclein Aggregation Pathway in Parkinson’s Disease: Current Status and Novel Therapeutic Approaches. Cells 2022, 11, 1732. [Google Scholar] [CrossRef] [PubMed]
- Jagadeesan, A.J.; Murugesan, R.; Vimala Devi, S.; Meera, M.; Madhumala, G.; Vishwanathan Padmaja, M.; Ramesh, A.; Banerjee, A.; Sushmitha, S.; Khokhlov, A.N.; et al. Current trends in etiology, prognosis and therapeutic aspects of Parkinson’s disease: A review. Acta Biomed. 2017, 88, 249–262. [Google Scholar] [PubMed]
- Bloem, B.R.; Okun, M.S.; Klein, C. Parkinson’s disease. Lancet 2021, 397, 2284–2303. [Google Scholar] [CrossRef] [PubMed]
- Radhakrishnan, D.; Goyal, V. Parkinson’s disease: A review. Neurol. India 2018, 66, 26. [Google Scholar]
- Reich, S.G.; Savitt, J.M. Parkinson’s Disease. Med. Clin. N. Am. 2019, 103, 337–350. [Google Scholar] [CrossRef] [PubMed]
- Schapira, A.H.V.; Chaudhuri, K.R.; Jenner, P. Non-motor features of Parkinson disease. Nat. Rev. Neurosci. 2017, 18, 435–450. [Google Scholar] [CrossRef] [PubMed]
- Pfeiffer, R.F. Non-motor symptoms in Parkinson’s disease. Park. Relat. Disord. 2016, 22, S119–S122. [Google Scholar] [CrossRef]
- Frisaldi, E.; Zamfira, D.A.; Benedetti, F. The subthalamic nucleus and the placebo effect in Parkinson’s disease. In Handbook of Clinical Neurology; Elsevier: Amsterdam, The Netherlands, 2021; pp. 433–444. [Google Scholar]
- Tekriwal, A.; Felsen, G.; Ojemann, S.G.; Abosch, A.; Thompson, J.A. Motor context modulates substantia nigra pars reticulata spike activity in patients with Parkinson’s disease. J. Neurol. Neurosurg. Psychiatry 2022, 93, 386–394. [Google Scholar] [CrossRef]
- Obeso, J.A.; Rodríguez-Oroz, M.C.; Benitez-Temino, B.; Blesa, F.J.; Guridi, J.; Marin, C.; Rodriguez, M. Functional organization of the basal ganglia: Therapeutic implications for Parkinson’s disease. Mov. Disord. 2008, 23, S548–S559. [Google Scholar] [CrossRef]
- Uceda, S.; Echeverry-Alzate, V.; Reiriz-Rojas, M.; Martínez-Miguel, E.; Pérez-Curiel, A.; Gómez-Senent, S.; Beltrán-Velasco, A.I. Gut Microbial Metabolome and Dysbiosis in Neurodegenerative Diseases: Psychobiotics and Fecal Microbiota Transplantation as a Therapeutic Approach—A Comprehensive Narrative Review. Int. J. Mol. Sci. 2023, 24, 13294. [Google Scholar] [CrossRef] [PubMed]
- Unger, M.M.; Spiegel, J.; Dillmann, K.U.; Grundmann, D.; Philippeit, H.; Bürmann, J.; Faßbender, K.; Schwiertz, A.; Schäfer, K.H. Short chain fatty acids and gut microbiota differ between patients with Parkinson’s disease and age-matched controls. Park. Relat. Disord. 2016, 32, 66–72. [Google Scholar] [CrossRef] [PubMed]
- Dowling, L.R.; Strazzari, M.R.; Keely, S.; Kaiko, G.E. Enteric nervous system and intestinal epithelial regulation of the gut-brain axis. J. Allergy Clin. Immunol. 2022, 150, 513–522. [Google Scholar] [CrossRef] [PubMed]
- Metta, V.; Leta, V.; Mrudula, K.R.; Prashanth, L.K.; Goyal, V.; Borgohain, R.; Chung-Faye, G.; Chaudhuri, K.R. Gastrointestinal dysfunction in Parkinson’s disease: Molecular pathology and implications of gut microbiome, probiotics, and fecal microbiota transplantation. J. Neurol. 2022, 269, 1154–1163. [Google Scholar] [CrossRef] [PubMed]
- Warnecke, T.; Schäfer, K.H.; Claus, I.; Del Tredici, K.; Jost, W.H. Gastrointestinal involvement in Parkinson’s disease: Pathophysiology, diagnosis, and management. NPJ Parkinson’s Dis. 2022, 8, 31. [Google Scholar] [CrossRef]
- Karunaratne, T.B.; Okereke, C.; Seamon, M.; Purohit, S.; Wakade, C.; Sharma, A. Niacin and Butyrate: Nutraceuticals Targeting Dysbiosis and Intestinal Permeability in Parkinson’s Disease. Nutrients 2020, 13, 28. [Google Scholar] [CrossRef]
- Kleine Bardenhorst, S.; Cereda, E.; Severgnini, M.; Barichella, M.; Pezzoli, G.; Keshavarzian, A.; Desideri, A.; Pietrucci, D.; Aho, V.T.E.; Scheperjans, F.; et al. Gut microbiota dysbiosis in Parkinson disease: A systematic review and pooled analysis. Eur. J. Neurol. 2023, 30, 3581–3594. [Google Scholar] [CrossRef] [PubMed]
- Hegelmaier, T.; Lebbing, M.; Duscha, A.; Tomaske, L.; Tönges, L.; Holm, J.B.; Nielsen, H.B.; Gatermann, S.G.; Przuntek, H.; Haghikia, A. Interventional Influence of the Intestinal Microbiome through Dietary Intervention and Bowel Cleansing Might Improve Motor Symptoms in Parkinson’s Disease. Cells 2020, 9, 376. [Google Scholar] [CrossRef] [PubMed]
- Chen, S.-J.; Chen, C.-C.; Liao, H.-Y.; Lin, Y.-T.; Wu, Y.-W.; Liou, J.-M.; Wu, M.-S.; Kuo, C.-H.; Lin, C.-H. Association of Fecal and Plasma Levels of Short-Chain Fatty Acids with Gut Microbiota and Clinical Severity in Patients with Parkinson Disease. Neurology 2022, 98, e848–e858. [Google Scholar] [CrossRef] [PubMed]
- Aho, V.T.E.; Houser, M.C.; Pereira, P.A.B.; Chang, J.; Rudi, K.; Paulin, L.; Hertzberg, V.; Auvinen, P.; Tansey, M.G.; Scheperjans, F. Relationships of gut microbiota, short-chain fatty acids, inflammation, and the gut barrier in Parkinson’s disease. Mol. Neurodegener. 2021, 16, 6. [Google Scholar] [CrossRef]
- Mirzaei, R.; Bouzari, B.; Hosseini-Fard, S.R.; Mazaheri, M.; Ahmadyousefi, Y.; Abdi, M.; Jalalifar, S.; Karimitabar, Z.; Teimoori, A.; Keyvani, H.; et al. Role of microbiota-derived short-chain fatty acids in nervous system disorders. Biomed. Pharmacother. 2021, 139, 111661. [Google Scholar] [CrossRef] [PubMed]
- Cryan, J.F.; O’Riordan, K.J.; Cowan, C.S.M.; Sandhu, K.V.; Bastiaanssen, T.F.S.; Boehme, M.; Codagnone, M.G.; Cussotto, S.; Fulling, C.; Golubeva, A.V.; et al. The Microbiota-Gut-Brain Axis. Physiol. Rev. 2019, 99, 1877–2013. [Google Scholar] [CrossRef] [PubMed]
- Shin, C.; Lim, Y.; Lim, H.; Ahn, T. Plasma Short-Chain Fatty Acids in Patients with Parkinson’s Disease. Mov. Disord. 2020, 35, 1021–1027. [Google Scholar] [CrossRef] [PubMed]
- Sampson, T.R.; Debelius, J.W.; Thron, T.; Janssen, S.; Shastri, G.G.; Ilhan, Z.E.; Challis, C.; Schretter, C.E.; Rocha, S.; Gradinaru, V.; et al. Gut Microbiota Regulate Motor Deficits and Neuroinflammation in a Model of Parkinson’s Disease. Cell 2016, 167, 1469–1480.e12. [Google Scholar] [CrossRef] [PubMed]
- Li, Z.; Liang, H.; Hu, Y.; Lu, L.; Zheng, C.; Fan, Y.; Wu, B.; Zou, T.; Luo, X.; Zhang, X.; et al. Gut bacterial profiles in Parkinson’s disease: A systematic review. CNS Neurosci. Ther. 2023, 29, 140–157. [Google Scholar] [CrossRef]
- Dinan, T.G.; Cryan, J.F. The Microbiome-Gut-Brain Axis in Health and Disease. Gastroenterol. Clin. N. Am. 2017, 46, 77–89. [Google Scholar] [CrossRef] [PubMed]
- Tansey, M.G.; Wallings, R.L.; Houser, M.C.; Herrick, M.K.; Keating, C.E.; Joers, V. Inflammation and immune dysfunction in Parkinson disease. Nat. Rev. Immunol. 2022, 22, 657–673. [Google Scholar] [CrossRef] [PubMed]
- Silva, Y.P.; Bernardi, A.; Frozza, R.L. The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication. Front. Endocrinol. 2020, 11, 508738. [Google Scholar] [CrossRef]
- Shen, T.; Yue, Y.; He, T.; Huang, C.; Qu, B.; Lv, W.; Lai, H.Y. The Association between the Gut Microbiota and Parkinson’s Disease, a Meta-Analysis. Front. Aging Neurosci. 2021, 13, 636545. [Google Scholar] [CrossRef]
- Wouters, M.M.; Gibbons, S.J.; Roeder, J.L.; Distad, M.; Ou, Y.; Strege, P.R.; Szurszewski, J.H.; Farrugia, G. Exogenous Serotonin Regulates Proliferation of Interstitial Cells of Cajal in Mouse Jejunum through 5-HT2B Receptors. Gastroenterology 2007, 133, 897–906. [Google Scholar] [CrossRef]
- Scheperjans, F.; Aho, V.; Pereira, P.A.B.; Koskinen, K.; Paulin, L.; Pekkonen, E.; Haapaniemi, E.; Kaakkola, S.; Eerola-Rautio, J.; Pohja, M.; et al. Gut microbiota are related to Parkinson’s disease and clinical phenotype. Mov. Disord. 2015, 30, 350–358. [Google Scholar] [CrossRef]
- Frost, G.; Sleeth, M.L.; Sahuri-Arisoylu, M.; Lizarbe, B.; Cerdan, S.; Brody, L.; Anastasovska, J.; Ghourab, S.; Hankir, M.; Zhang, S.; et al. The short-chain fatty acid acetate reduces appetite via a central homeostatic mechanism. Nat. Commun. 2014, 5, 3611. [Google Scholar] [CrossRef] [PubMed]
- Clarke, G.; Stilling, R.M.; Kennedy, P.J.; Stanton, C.; Cryan, J.F.; Dinan, T.G. Minireview: Gut Microbiota: The Neglected Endocrine Organ. Mol. Endocrinol. 2014, 28, 1221–1238. [Google Scholar] [CrossRef]
- Hirayama, M.; Ohno, K. Parkinson’s Disease and Gut Microbiota. Ann. Nutr. Metab. 2021, 77 (Suppl. S2), 28–35. [Google Scholar] [CrossRef] [PubMed]
- Oleskin, A.V.; Shenderov, B.A. Neuromodulatory effects and targets of the SCFAs and gasotransmitters produced by the human symbiotic microbiota. Microb. Ecol. Health Dis. 2016, 27, 30971. [Google Scholar] [CrossRef]
- Hooijmans, C.R.; Rovers, M.M.; de Vries, R.B.; Leenaars, M.; Ritskes-Hoitinga, M.; Langendam, M.W. SYRCLE’s risk of bias tool for animal studies. BMC Med. Res. Methodol. 2014, 14, 43. [Google Scholar] [CrossRef]
- Vernon, A.C.; Croucher, M.J.; Dexter, D.T. Additive neuroprotection by metabotropic glutamate receptor subtype-selective ligands in a rat Parkinson’s model. Neuroreport 2008, 19, 475–478. [Google Scholar] [CrossRef] [PubMed]
- Zhou, W.; Bercury, K.; Cummiskey, J.; Luong, N.; Lebin, J.; Freed, C.R. Phenylbutyrate Up-regulates the DJ-1 Protein and Protects Neurons in Cell Culture and in Animal Models of Parkinson Disease. J. Biol. Chem. 2011, 286, 14941–14951. [Google Scholar] [CrossRef]
- Kuruvilla, K.P.; Nandhu, M.S.; Paul, J.; Paulose, C.S. Oxidative stress mediated neuronal damage in the corpus striatum of 6-hydroxydopamine lesioned Parkinson’s rats: Neuroprotection by Serotonin, GABA and Bone Marrow Cells Supplementation. J. Neurol. Sci. 2013, 331, 31–37. [Google Scholar] [CrossRef]
- Ji, L.; Huang, T.; Mao, L.; Xu, Y.; Chen, W.; Wang, W.; Wang, L.H. The gut microbiota metabolite butyrate mitigates MPTP/MPP + -induced Parkinson’s disease by inhibiting the JAK2/STAT3 signaling pathway. Kaohsiung J. Med. Sci. 2023, 39, 1002–1010. [Google Scholar] [CrossRef]
- Tieu, K.; Perier, C.; Caspersen, C.; Teismann, P.; Wu, D.-C.; Yan, S.-D.; Naini, A.; Vila, M.; Jackson-Lewis, V.; Ramasamy, R.; et al. D-β-Hydroxybutyrate rescues mitochondrial respiration and mitigates features of Parkinson disease. J. Clin. Investig. 2003, 112, 892–901. [Google Scholar] [CrossRef] [PubMed]
- Liu, J.; Wang, F.; Liu, S.; Du, J.; Hu, X.; Xiong, J.; Fang, R.; Chen, W.; Sun, J. Sodium butyrate exerts protective effect against Parkinson’s disease in mice via stimulation of glucagon like peptide-1. J. Neurol. Sci. 2017, 381, 176–181. [Google Scholar] [CrossRef] [PubMed]
- Johnson, J.; Pajarillo, E.A.B.; Taka, E.; Reams, R.; Son, D.S.; Aschner, M.; Lee, E. Valproate and sodium butyrate attenuate manganese-decreased locomotor activity and astrocytic glutamate transporters expression in mice. Neurotoxicology 2018, 64, 230–239. [Google Scholar] [CrossRef] [PubMed]
- Srivastav, S.; Neupane, S.; Bhurtel, S.; Katila, N.; Maharjan, S.; Choi, H.; Hong, J.T.; Choi, D.-Y. Probiotics mixture increases butyrate, and subsequently rescues the nigral dopaminergic neurons from MPTP and rotenone-induced neurotoxicity. J. Nutr. Biochem. 2019, 69, 73–86. [Google Scholar] [CrossRef] [PubMed]
- Dong, X.-L.; Wang, X.; Liu, F.; Liu, X.; Du, Z.-R.; Li, R.W.; Xue, C.-H.; Wong, K.-H.; Wong, W.-T.; Zhao, Q.; et al. Polymannuronic acid prevents dopaminergic neuronal loss via brain-gut-microbiota axis in Parkinson’s disease model. Int. J. Biol. Macromol. 2020, 164, 994–1005. [Google Scholar] [CrossRef] [PubMed]
- Hou, Y.; Li, X.; Liu, C.; Zhang, M.; Zhang, X.; Ge, S.; Zhao, L. Neuroprotective effects of short-chain fatty acids in MPTP induced mice model of Parkinson’s disease. Exp. Gerontol. 2021, 150, 111376. [Google Scholar] [CrossRef]
- Avagliano, C.; Coretti, L.; Lama, A.; Pirozzi, C.; De Caro, C.; De Biase, D.; Turco, L.; Mollica, M.P.; Paciello, O.; Calignano, A.; et al. Dual-Hit Model of Parkinson’s Disease: Impact of Dysbiosis on 6-Hydroxydopamine-Insulted Mice—Neuroprotective and Anti-Inflammatory Effects of Butyrate. Int. J. Mol. Sci. 2022, 23, 6367. [Google Scholar] [CrossRef]
- Xu, R.-C.; Miao, W.-T.; Xu, J.-Y.; Xu, W.-X.; Liu, M.-R.; Ding, S.-T.; Jian, Y.-X.; Lei, Y.-H.; Yan, N.; Liu, H.-D. Neuroprotective Effects of Sodium Butyrate and Monomethyl Fumarate Treatment through GPR109A Modulation and Intestinal Barrier Restoration on PD Mice. Nutrients 2022, 14, 4163. [Google Scholar] [CrossRef]
- Guo, T.-T.; Zhang, Z.; Sun, Y.; Zhu, R.-Y.; Wang, F.-X.; Ma, L.-J.; Jiang, L.; Liu, H.-D. Neuroprotective Effects of Sodium Butyrate by Restoring Gut Microbiota and Inhibiting TLR4 Signaling in Mice with MPTP-Induced Parkinson’s Disease. Nutrients 2023, 15, 930. [Google Scholar] [CrossRef]
- Wang, Y.; Chen, W.; Han, Y.; Xu, X.; Yang, A.; Wei, J.; Hong, D.; Fang, X.; Chen, T. Neuroprotective effect of engineered Clostridium butyricum-pMTL007-GLP-1 on Parkinson’s disease mice models via promoting mitophagy. Bioeng. Transl. Med. 2023, 8, e10505. [Google Scholar] [CrossRef]
- Liu, P.; Wang, Y.; Yang, G.; Zhang, Q.; Meng, L.; Xin, Y.; Jiang, X. The role of short-chain fatty acids in intestinal barrier function, inflammation, oxidative stress, and colonic carcinogenesis. Pharmacol. Res. 2021, 165, 105420. [Google Scholar] [CrossRef]
- Huang, W.; Guo, H.L.; Deng, X.; Zhu, T.T.; Xiong, J.F.; Xu, Y.H.; Xu, Y. Short-Chain Fatty Acids Inhibit Oxidative Stress and Inflammation in Mesangial Cells Induced by High Glucose and Lipopolysaccharide. Exp. Clin. Endocrinol. Diabetes 2017, 125, 98–105. [Google Scholar] [CrossRef] [PubMed]
- Lanza, M.; Campolo, M.; Casili, G.; Filippone, A.; Paterniti, I.; Cuzzocrea, S.; Esposito, E. Sodium Butyrate Exerts Neuroprotective Effects in Spinal Cord Injury. Mol. Neurobiol. 2019, 56, 3937–3947. [Google Scholar] [CrossRef] [PubMed]
- Iyer, S.M.; Verma, S.; Marathe, S.A.; Tare, M. Emerging Relationship between the Gut Microbiota and Neurodegenerative Disorders. In Altered Metabolism: A Major Contributor of Comorbidities in Neurodegenerative Diseases; Springer Nature Singapore: Singapore, 2024; pp. 271–301. [Google Scholar]
- Zhang, X.; Tang, B.; Guo, J. Parkinson’s disease and gut microbiota: From clinical to mechanistic and therapeutic studies. Transl. Neurodegener. 2023, 12, 59. [Google Scholar] [CrossRef]
- Zhang, D.; Jian, Y.P.; Zhang, Y.N.; Li, Y.; Gu, L.T.; Sun, H.H.; Liu, M.-D.; Zhou, H.-L.; Wang, Y.-S.; Xu, Z.-X. Short-chain fatty acids in diseases. Cell Commun. Signal. 2023, 21, 212. [Google Scholar] [CrossRef] [PubMed]
- Zhang, Y.; Xu, S.; Qian, Y.; Mo, C.; Ai, P.; Yang, X.; Xiao, Q. Sodium butyrate ameliorates gut dysfunction and motor deficits in a mouse model of Parkinson’s disease by regulating gut microbiota. Front. Aging Neurosci. 2023, 15, 1099018. [Google Scholar] [CrossRef]
- Hediger, M.A.; Kanai, Y.; You, G.; Nussberger, S. Mammalian ion-coupled solute transporters. J. Physiol. 1995, 482, 7–17. [Google Scholar] [CrossRef] [PubMed]
- Licciardi, P.V.; Ververis, K.; Karagiannis, T.C. Histone Deacetylase Inhibition and Dietary Short-Chain Fatty Acids. Int. Sch. Res. Not. 2011, 2011, 869647. [Google Scholar] [CrossRef] [PubMed]
- Dong, Y.; Qi, Y.; Chen, J.; Han, S.; Su, W.; Ma, X.; Yu, Y.; Wang, Y. Neuroprotective Effects of Bifidobacterium animalis subsp. lactis NJ241 in a Mouse Model of Parkinson’s Disease: Implications for Gut Microbiota and PGC-1α. Mol. Neurobiol. 2024. [Google Scholar] [CrossRef] [PubMed]
- Parada Venegas, D.; De la Fuente, M.K.; Landskron, G.; González, M.J.; Quera, R.; Dijkstra, G.; Harmsen, H.J.M.; Faber, K.N.; Hermoso, M.A. Short Chain Fatty Acids (SCFAs)-Mediated Gut Epithelial and Immune Regulation and Its Relevance for Inflammatory Bowel Diseases. Front. Immunol. 2019, 10, 277. [Google Scholar]
- Elford, J.D.; Becht, N.; Garssen, J.; Kraneveld, A.D.; Perez-Pardo, P. Buty and the beast: The complex role of butyrate in Parkinson’s disease. Front. Pharmacol. 2024, 15, 1388401. [Google Scholar] [CrossRef] [PubMed]
- Liu, X.; Du, Z.R.; Wang, X.; Sun, X.R.; Zhao, Q.; Zhao, F.; Wong, W.T.; Wong, K.H.; Dong, X.-L. Polymannuronic acid prebiotic plus Lacticaseibacillus rhamnosus GG probiotic as a novel synbiotic promoted their separate neuroprotection against Parkinson’s disease. Food Res. Int. 2022, 155, 111067. [Google Scholar] [CrossRef] [PubMed]
- Page, M.J.; McKenzie, J.E.; Bossuyt, P.M.; Boutron, I.; Hoffmann, T.C.; Mulrow, C.D.; Shamseer, L.; Tetzlaff, J.M.; Moher, D. Updating guidance for reporting systematic reviews: Development of the PRISMA 2020 statement. J. Clin. Epidemiol. 2021, 134, 103–112. [Google Scholar] [CrossRef] [PubMed]
- Beltrán-Velasco, A.I.; Reiriz, M.; Uceda, S.; Echeverry-Alzate, V. Lactiplantibacillus (Lactobacillus) plantarum as a Complementary Treatment to Improve Symptomatology in Neurodegenerative Disease: A Systematic Review of Open Access Literature. Int. J. Mol. Sci. 2024, 25, 3010. [Google Scholar] [CrossRef] [PubMed]
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Missiego-Beltrán, J.; Olalla-Álvarez, E.M.; González-Brugera, A.; Beltrán-Velasco, A.I. Implications of Butyrate Signaling Pathways on the Motor Symptomatology of Parkinson’s Disease and Neuroprotective Effects—Therapeutic Approaches: A Systematic Review. Int. J. Mol. Sci. 2024, 25, 8998. https://doi.org/10.3390/ijms25168998
Missiego-Beltrán J, Olalla-Álvarez EM, González-Brugera A, Beltrán-Velasco AI. Implications of Butyrate Signaling Pathways on the Motor Symptomatology of Parkinson’s Disease and Neuroprotective Effects—Therapeutic Approaches: A Systematic Review. International Journal of Molecular Sciences. 2024; 25(16):8998. https://doi.org/10.3390/ijms25168998
Chicago/Turabian StyleMissiego-Beltrán, Jorge, Eva María Olalla-Álvarez, Ana González-Brugera, and Ana Isabel Beltrán-Velasco. 2024. "Implications of Butyrate Signaling Pathways on the Motor Symptomatology of Parkinson’s Disease and Neuroprotective Effects—Therapeutic Approaches: A Systematic Review" International Journal of Molecular Sciences 25, no. 16: 8998. https://doi.org/10.3390/ijms25168998