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Review
. 2022 Jul 6;23(14):7503.
doi: 10.3390/ijms23147503.

Impact of Nutrition, Microbiota Transplant and Weight Loss Surgery on Dopaminergic Alterations in Parkinson's Disease and Obesity

Sevag Hamamah  1 , Andras Hajnal  2 , Mihai Covasa  1   3
Affiliations
Review

Impact of Nutrition, Microbiota Transplant and Weight Loss Surgery on Dopaminergic Alterations in Parkinson's Disease and Obesity

Sevag Hamamah et al. Int J Mol Sci. .

Abstract

Parkinson's disease (PD), the second most common neurodegenerative disorder worldwide, is characterized by dopaminergic neuron degeneration and α-synuclein aggregation in the substantia nigra pars compacta of the midbrain. Emerging evidence has shown that dietary intake affects the microbial composition in the gut, which in turn contributes to, or protects against, the degeneration of dopaminergic neurons in affected regions of the brain. More specifically, the Mediterranean diet and Western diet, composed of varying amounts of proteins, carbohydrates, and fats, exert contrasting effects on PD pathophysiology via alterations in the gut microbiota and dopamine levels. Interestingly, the negative changes in the gut microbiota of patients with PD parallel changes that are seen in individuals that consume a Western diet, and are opposite to those that adhere to a Mediterranean diet. In this review, we first examine the role of prominent food groups on dopamine bioavailability, how they modulate the composition and function of the gut microbiota and the subsequent effects on PD and obesity pathophysiology. We then highlight evidence on how microbiota transplant and weight loss surgery can be used as therapeutic tools to restore dopaminergic deficits through optimizing gut microbial composition. In the process, we revisit dietary metabolites and their role in therapeutic approaches involving dopaminergic pathways. Overall, understanding the role of nutrition on dopamine bioavailability and gut microbiota in dopamine-related pathologies such as PD will help develop more precise therapeutic targets to rescue dopaminergic deficits in neurologic and metabolic disorders.

Keywords: Mediterranean diet; Roux-en-Y gastric bypass; Western diet; gut microbiota; microbiota transfer; weight loss surgery.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Effects of food groups on gut microbiota. FOS increase Bifidobacterium and Lactobacillus species in the gut [35]. HFCS and sucrose administration increases Prevotella and Proteobacteria while decreasing Bacteroidetes [36]. Omega-3 PUFA increase Lactobacillus and Bacteroidetes [37]. Animal-based proteins increase Bacteroides and Desulfovibrio while decreasing Bifidobacterium, Roseburia and Blautia [38,39]. Plant-based proteins increase Bifidobacterium and Lactobacillus [40]. Abbreviations: FOS, fructo-oligosaccharides; HFCS, high-fructose corn syrup; PUFA, poly-unsaturated fatty acids.
Figure 2
Figure 2
Effects of food groups on dopamine. FOS consumption increases dopamine levels in the NAc and the cortex [46,47]. Acute HFCS and sucrose consumption increases dopamine in the NAc [48]. Chronic HFCS and sucrose consumption decreases D2R expression, D2R binding affinity, striatal dopamine levels and TH in the medial PFC [50,52]. Omega-3 PUFA increase BDNF and TH+ cells in the VTA and NAc [57]. Omega-3 PUFA decrease dopamine neuron loss in the SNpc and striatum [58], while also reducing reward seeking behavior [59]. Protein intake increases dopamine synthesis, dopamine levels in the NAc and HVA concentrations while decreasing post-meal cravings [60,61,62]. Abbreviations: FOS, fructo-oligosaccharides; HFCS, high-fructose corn syrup; PUFA, poly-unsaturated fatty acids, DA, dopamine; NAc, nucleus accumbens; D2R, dopamine 2 receptor; TH, tyrosine hydroxylase; PFC, pre-frontal cortex; BDNF, brain derived neurotrophic factor; VTA, ventral tegmental area; SNpc, substantia nigra pars compacta; HVA, homovanillic acid.
Figure 3
Figure 3
The effects of the Mediterranean Diet and Western Diet on gut microbiota and Parkinson’s Disease. The MD is composed of Omega-3 PUFA, plant protein, grains, and nuts. The MD increases concentrations of Roseburia, Faecalibacterium prausnitzii and Eubacterium, while lowering concentrations of Bilophila, Ruminococcus torques, Coprococcus comes. The MD effects on PD include delaying onset, improving executive function in PD patients, upregulating BDNF production, alleviating inflammation, improving intestinal barrier integrity and stimulating GLP-1 secretion, which in turn increases DAT expression and reduces dopaminergic neuron death. The WD is composed of animal proteins, fats and sugars. The WD increases concentrations of Ruminococcus torques and Escherichia coli, while reducing levels of Eubacterium, Roseburia and Bifidobacterium in the gut. The WD effects on PD include promoting gut inflammation via LPS/TLR4 activity, NLRP3 inflammasome innate reprogramming, increasing neuroinflammation, reducing striatal dopamine and D2R, leading to nigrostriatal dopaminergic loss and α-synuclein accumulation. Abbreviations: PUFA, poly-unsaturated fatty acids; BDNF, brain derived neurotrophic factor; GLP-1, glucagon-like peptide 1; DAT, dopamine transporter; LPS, lipopolysaccharides; TLR-4, toll-like receptor 4; D2R, dopamine 2 receptor.
Figure 4
Figure 4
Gut-brain changes in Parkinson’s Disease and restoration of dopaminergic and Parkinson’s disease deficits via fecal microbiota transplant and weight loss surgery. Changes in the brain include decreased BDNF levels, reduced tyrosine hydroxylase expression, increased α-synuclein and microglial activity. Changes in the gut include increased intestinal permeability, mucin-degradation and α-synucleins, LPS secretion and pro-inflammatory cytokines. Fecal microbiota transplant increases striatal dopamine concentrations, VTA dopamine excitability and BDNF, while decreasing p-cresol levels and microglial activity. Weight loss surgery increases DAT expression, D2R/D3R expression, GLP-1 levels, and striatal dopamine concentrations. Abbreviations: BDNF, brain derived neurotrophic factor; TH, tyrosine hydroxylase; LPS, lipopolysaccharide; TNF-α, tumor necrosis factor α; TLR-4, toll-like receptor 4; VTA, ventral tegmental area; DAT, dopamine transporter; D2R, dopamine 2 receptor; D3R, dopamine 3 receptor; DAT, dopamine transporter; GLP-1, glucagon-like peptide 1; FMT, fecal microbiota transplant; WLS, weight loss surgery.
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