Submitted Successfully!
To reward your contribution, here is a gift for you: A free trial for our video production service.
Thank you for your contribution! You can also upload a video entry or images related to this topic.
Version Summary Created by Modification Content Size Created at Operation
1 -- 4844 2022-10-27 23:05:29 |
2 format corrected. -2 word(s) 4842 2022-10-31 03:44:54 |

Video Upload Options

Do you have a full video?

Confirm

Are you sure to Delete?
Cite
If you have any further questions, please contact Encyclopedia Editorial Office.
Varesi, A.;  Campagnoli, L.I.M.;  Fahmideh, F.;  Pierella, E.;  Romeo, M.;  Ricevuti, G.;  Nicoletta, M.;  Chirumbolo, S.;  Pascale, A. Therapeutic Approaches for Parkinson’s Disease and Gut Microbiota. Encyclopedia. Available online: https://encyclopedia.pub/entry/31673 (accessed on 15 April 2024).
Varesi A,  Campagnoli LIM,  Fahmideh F,  Pierella E,  Romeo M,  Ricevuti G, et al. Therapeutic Approaches for Parkinson’s Disease and Gut Microbiota. Encyclopedia. Available at: https://encyclopedia.pub/entry/31673. Accessed April 15, 2024.
Varesi, Angelica, Lucrezia Irene Maria Campagnoli, Foroogh Fahmideh, Elisa Pierella, Marcello Romeo, Giovanni Ricevuti, Marchesi Nicoletta, Salvatore Chirumbolo, Alessia Pascale. "Therapeutic Approaches for Parkinson’s Disease and Gut Microbiota" Encyclopedia, https://encyclopedia.pub/entry/31673 (accessed April 15, 2024).
Varesi, A.,  Campagnoli, L.I.M.,  Fahmideh, F.,  Pierella, E.,  Romeo, M.,  Ricevuti, G.,  Nicoletta, M.,  Chirumbolo, S., & Pascale, A. (2022, October 27). Therapeutic Approaches for Parkinson’s Disease and Gut Microbiota. In Encyclopedia. https://encyclopedia.pub/entry/31673
Varesi, Angelica, et al. "Therapeutic Approaches for Parkinson’s Disease and Gut Microbiota." Encyclopedia. Web. 27 October, 2022.
Therapeutic Approaches for Parkinson’s Disease and Gut Microbiota
Edit

The bidirectional interaction between the gut microbiota (GM) and the Central Nervous System, the so-called gut microbiota brain axis (GMBA), deeply affects brain function and has an important impact on the development of neurodegenerative diseases. In Parkinson’s disease (PD), gastrointestinal symptoms often precede the onset of motor and non-motor manifestations, and alterations in the GM composition accompany disease pathogenesis. Several studies have been conducted to unravel the role of dysbiosis and intestinal permeability in PD onset and progression, but the therapeutic and diagnostic applications of GM modifying approaches remain to be fully elucidated. 

Parkinson’s disease gut microbiota dysbiosis intestinal permeability diagnosis probiotics

1. Gut Microbiota-Based PD Interventions: Antibiotics

Antibiotics are chemical compounds able to kill or arrest the growth of certain microorganisms. Although they are mainly used to counteract or prevent bacterial infections, their additional anti-inflammatory, immunomodulator, neuroprotective, antiamyloidogenic and antioxidant properties are becoming of increasing interest in the context of neurological disorders, including neurodegeneration [1][2][3][4][5]. Indeed, beside counteracting dysbiosis and constipation [6], it has been demonstrated that certain antibiotics can inhibit the activity of matrix metalloproteinases and prevent mitochondria dysfunction, microglia activation, protein misfolding and α-synuclein aggregation [7][8][9][10][11]. For example, treating mice where Parkinson’s disease (PD) has been induced by MPTP with a cocktail of broad-spectrum antibiotics (ampicillin, metronidazole, and neomycin sulfate) was found to preserve TH and dopamine transporter immunoreactivities, which are generally lost upon MPTP administration [12]. This beneficial effect is mediated by an increase in Proteobacteria, as well as by a decrease in Deferribacteres and Saccharibacteria (TM7) abundance, which reflect an altered gut microbiota (GM) composition characterized by diversity loss [12]. Similar results were obtained in 6-OHDA-induced PD rats upon chronic treatment with an antibiotic mixture containing neomycin, pimaricin, bacitracin and vancomycin, which prevented dopaminergic neuronal death, relieved inflammation, ameliorated neurotoxicity and reduced motor impairments as measured by cylinder, rotation and stepping tests [13]. Recently, Cui et al. reported that vancomycin pretreatment of MPTP-induced PD mice improved motor symptoms by reducing SN astrocytes and microglia activation [14]. Notably, the authors proposed that neuroinflammation is indirectly inhibited by Akkermansia and Blautia, which increase in abundance upon vancomycin treatment and interfere with the toll like receptor 4 (TLR-4)/NF-κB pathway in the gut and in the brain [14]. Although Akkermansia is generally reported as harmful in PD patients, its dual negative and positive role may lean towards the latter when mucin conversion into SCFAs prevails over gut-barrier degradation, thus explaining this apparent discrepancy. In humans, an intestinal decontamination therapy consisting of sodium phosphate enema, oral rifaximin and polyethylene glycol resulted effective in reducing dyskinesia and motor fluctuations related to PD, but more studies are required [15]. Other approaches focused on the use of certain specific antibiotics instead of cocktails have also been proposed to maximize the therapeutic benefit without impacting beneficial bacteria.
Rifaximin is a broad spectrum antibiotic with poor systemic absorption indicated to treat SIBO [6][16][17]. In this respect, rifaximin-mediated SIBO eradication in PD patients resulted in reduced motor fluctuations without impacting on L-dopa treatment [18]. This benefit should be ascribed to rifaximin-mediated modulation of the brain thyrotropin releasing hormone (THR) and THR-like peptides, which have caloric-restriction-like, anti-aging, neuroprotective properties and are known to be involved in the gut-brain axis [19]. However, no improvement in GI symptoms in 8 PD patients treated with rifaximin poses controversy over the actual efficacy of this antibiotic as PD treatment, calling for new studies [20].
Ceftriaxone (CTX) is a β-lactam antibiotic with a strong and safe past record [21][22]. The treatment of several PD animal models with CTX is known to improve neuroinflammatory and oxidative stress markers, stimulate neurogenesis and promote astrocyte viability through the suppression of NF-κB/c-Jun-mediated signaling [21][22][23][24]. Mechanistically, CTX also reduces extracellular glutamate levels by increasing the expression of the glutamate transporter-1 in astrocytes, thus avoiding brain excitotoxicity [22][24][25]. Moreover, it has been observed that CTX binds to α-synuclein with considerable affinity and prevents its polymerization in vitro [22][26][27]. in vivo, there is evidence that CTX treatment modifies the GM composition of MPTP-induced PD mice by disadvantaging the growth of Proteus while increasing the relative abundance of Akkermansia species, which act as probiotics when their SCFAs-converting activity exceeds that of intestinal barrier degradation [28].
Further studies proved the ability of CTX to reduce the levels of the main pro-inflammatory mediators TLR-4, MyD88 (myeloid differentiation primary response 88), IL-1β, TNF-α and NF-κB in the brain, TLR-4, MyD88, and NF-κB in the colon and IL-1β, TNF-α and IL-6 in the serum [28][29][30]. Similarly, CTX-mediated increase in the main antioxidant modulators glutathione, superoxide dismutase (SOD) and catalase was found to prevent the oxidative damage observed in rats treated with MPTP [29][30]. In line with these data, CTX administration was associated with reduced glial fibrillary acid protein (GFAP) and ionized calcium-binding adapter molecule 1 (IBA-1) expression, two markers of astrogliosis and microglia activation, respectively [28][31][32][33]. At the neuronal level, pre- or post- treatment with CTX prevented the loss of TH-positive neurons, reduced glutamatergic hyperactivity, and promoted neurogenesis at the level of SN and hippocampal dentate gyrus in different rat models of the disease [29][33][34][35][36][37][38]. As a consequence, dyskinesia, motor impairment and memory loss were all reverted upon CTX administration [29][30][33][34][35][36][38][39][40], although conflicting evidence still remains about its ability to improve learning outcomes [41]. Of note, CTX has been shown to interact synergistically with other compounds currently used or under investigation for the treatment of PD, such as erythropoietin, ropinirole and memantine, but the safety as well as the efficacy of these combinations should be further assessed [29][30][42].
Minocycline is a second-generation semisynthetic tetracycline with anti-microbial, anti-apoptotic, anti-inflammatory and antioxidant properties [43][44][45][46]. Thanks to the ability to efficiently cross the BBB, minocycline is considered neuroprotective for a variety of neurological conditions, including PD [47][48][49][50][51][52][53]. This effect is mainly ascribable to the minocycline-dependent suppression of microglia activation, which has been reported by several in vivo studies [47][54][55][56][57][58][59]. In this respect, microglial inactivation by minocycline correlates with decreased IL-1β formation, as well as reduced NADPH-oxidase and inducible nitric oxide synthase (iNOS) activity, suggesting that both anti-inflammatory and antioxidant pathways are involved [58][60]. In vitro, minocycline addition to 6-OHDA treated PC12 cells suppresses the release of lactate dehydrogenase, reactive oxygen species (ROS) and caspase 3 while supporting the activity of the antioxidant enzymes SOD and catalase [47][61][62][63]. Of note, these molecular changes seem to explain the increased striatal dopamine levels as well as the cognitive and locomotor improvements observed in zebrafish, mouse, and rat models [55][56][60][64][65][66][67]. Another mechanism through which minocycline prevents apoptosis is by limiting mitochondria dysfunction, inhibiting caspase 1 and 3 expression, and preventing the degradation of the antiapoptotic protein ICAD (the inhibitor of the caspase-activated deoxyribonuclease) [47][68][69][70]. However, despite the promising results, controversy remains. Indeed, an enhanced toxicity has been reported upon minocycline administration to MPTP-treated rodents and primates, resulting in disease exacerbation [71][72]. Moreover, results from a phase II clinical trial show no benefit from the use of minocycline and evidence decreased tolerability, although more studies are needed before drawing premature conclusions [73][74].
Doxycycline (DOX) is another broad-spectrum antibiotic belonging to tetracyclines that has been considered as PD treatment [75]. In vitro, DOX has shown anti-inflammatory properties by interfering with p38 MAP kinase and NF-κB pathways, reducing the expression of the activated microglia marker IBA-1 and inhibiting the production of the pro-oxidant and pro-inflammatory factors ROS, nitric oxide, iNOS, cyclooxygenase-2 (COX-2), IL-1β and TNF-α [76][77][78]. Concerning neuroprotection, DOX exerts an anti-apoptotic activity by repressing the matrix metallopeptidase-3 (MMP-3) in dopaminergic neurons and microglia both in vitro and in vivo [77]. In addition, DOX stimulates neurite growth through the activation of PI3K/Akt and MAPK/ERK pathways, independently from nerve growth factor activity [79]. Of note, recent studies demonstrated that DOX reduces the size and load of α-synuclein oligomers by converting them into high-molecular weight species that are not able to form fibrils, thus increasing cell viability [78][80]. When tested in vivo, DOX confirmed its neuroprotective activity by limiting dopaminergic neuronal loss in SN while increasing striatal dopamine levels [81][82]. This beneficial function is achieved by contrasting glial reactivity and by reducing the major histocompatibility complex-II expression in microglial cells [81][82]. In 6-OHDA-treated rats, both DOX and its derivative COL-3 showed an anti-dyskinetic potential when administered in combination with L-dopa [83]. According to the authors, the reduced levels of MMP-2/-9, MMP-3, ROS and of the dyskinesia-linked immunoreactivity markers FOSB, COX-2, GFAP and OX-42 would explain these benefits [83]. Nevertheless, despite promising in vivo data, clinical evidence is still lacking.
Rifampicin is a macrocyclic antibiotic with cytoprotective functions that have been considered for PD treatment [84][85]. Indeed, there is evidence that rifampicin prevents α-synuclein fibrillation by promoting SUMOylation, which increases fibril solubility preventing neuronal death [86][87][88]. Other studies reported a reduction in IL-1β, TNF-α, IL-6 and ROS released by cells double treated with rotenone and rifampicin, thus indicating a promotion of neuroprotection [89][90][91]. Although not completely defined, rifampicin appears to sustain cell viability through different mechanisms: (i) by enhancing autophagy [89][91]; (ii) via PI3K/Akt/GSK-3β/CREB pathway modulation [92]; (iii) by upregulating the unfolded protein response marker GRP78 through the PERK/eIF2α/ATF4 pathway [93]. In vivo, MPTP-induced PD mice treated with rifampicin showed increased striatal and SN TH immunoreactivity, attenuated levels of oxidative stress and re-established dopaminergic signaling in the striatum [94]. More recently, rotenone-induced PD in zebrafish has shown benefit from rifampicin administration due to the decrease in neuroinflammation [95].
Generally, although promising, two main concerns remain about the use of antibiotics in PD treatment: (i) antibiotics can kill some specific microbial populations leading to intestinal dysbiosis and neurological dysfunction and (ii) their prolonged and widespread intake would favor antibiotic resistance [9][96][97]. There is evidence that ceftriaxone (a third-generation cephalosporin)-induced dysbiosis worsens motor symptoms in 6-OHDA treated mice and correlates with dopaminergic neuron toxicity as well as intestinal and systemic inflammation [98]. Moreover, quinolones and β-lactams are known to trigger neurotoxicity through their interference with gamma-aminobutyric acid and benzodiazepine receptors signaling [9]. Mechanistically, it has been hypothesized that antibiotic-induced dysbiosis may favor the growth of Enterobacteria producing the bacterial α-synuclein curli, which promotes neurodegeneration [99][100]. In addition, leaky gut-mediated systemic inflammation might result from dysbiosis and mediate the BBB damage, allowing circulating neurotoxins to enter the brain [101]. In humans, a Finnish study conducted on 13,976 PD and 40,697 healthy individuals showed that taking certain antibiotics years earlier, especially macrolides and lincosamides, correlates with an increased risk of developing PD [102]. However, results from another prospective study involving 59,637 women did not report any correlation between antibiotic intake and PD incidence [103]. Overall, contrasting results and scarce long-term safety data remain a concern. Innovative drug delivery systems based on nanoparticles are now being tested to improve the clinical benefit of these antibiotics [75]. At the same time, synthetic tailoring to potentiate the neuroprotective chemical functions over the antimicrobial ones is another promising approach for the risk-benefit optimization [97].

2. Gut Microbiota-Based PD Interventions: Probiotics

Probiotics are defined as “live microorganisms that, when administered in adequate amounts, confer a health benefit on the host” [104]. It is widely reported that the most common bacteria used as probiotics (Lactobacilli, Bifidobacteria, and Enterococci) [105] have potential benefits in restoring the GM, reducing intestinal permeability, inflammation, and oxidative stress, improving immune homeostasis and GI symptoms (constipation, diarrhoea, bloating, and abdominal pain), as well as preventing or counteracting several conditions, including GI, liver, and cardiovascular diseases, obesity, diabetes, cancer, and H. pylori and urogenital infections [11][106][107][108][109]. Moreover, it is now evident that GM dysbiosis is a factor that takes part in the development of several neurological diseases, including PD, AD, multiple sclerosis, autism spectrum disorders (ASD), anxiety, depression, schizophrenia, and other mental illnesses [110][111]. Concerning PD, as previously mentioned, altered GM could contribute to the onset of some PD-related complications, such as constipation, the most common non-motor symptom [112]. Therefore, modulation of the microbiota-gut-brain axis using probiotics could be a promising complementary approach to traditional methods to prevent or counteract these disorders, including PD, as widely reported in literature [111][113][114][115][116]. For instance, Bacteroides fragilis has been documented to improve ASD symptoms and gut barrier integrity, and reduce intestinal permeability [117]; further, the probiotic SLAB51, a formulation of nine live bacterial strains (Streptococcus thermophilus, B. longum, B. breve, B. infantis, L. acidophilus, L. plantarum, L. paracasei, L. delbrueckii subsp. bulgaricus, and L. brevis) improves cognition and reduces the accumulation of amyloid plaques, brain injury, and inflammatory cytokines plasma levels in AD mice [118], while the assumption of a probiotic fermented milk drink containing L. acidophilus, L. casei, B. bifidum, and L. fermentum improves cognitive function in AD patients [119]. Concerning PD, many studies showed that probiotic intake can reduce neuroinflammation, inhibit the loss of dopaminergic neurons, and modulate brain functions.

3. Gut Microbiota-Based PD Interventions: Prebiotics

According to the International Scientific Association for Probiotics and Prebiotics (ISAPP), prebiotics are defined as “substrates selectively used by host microorganisms that confer health benefits to the host, while retaining the microflora-mediated health benefits” [120]. Prebiotics are dietary fibres originated from soybeans, raw oats, unrefined wheat and barley, non-digestible carbohydrates and oligosaccharides, including galacto-oligosaccharides (GOS), fructo-oligosaccharides (FOS), inulin, and lactulose [121][122]. Polyphenols (catechin, epicatechin and quercetin) can also act as prebiotics [123]. They can alter GM composition, by favouring the growth and the activity of beneficial bacteria, and by decreasing pathogens in the GI tract; further, they have positive effects on lipid metabolism, decrease the recurrence of Clostridium difficile infections, and alleviate GI and allergic disorders [124][125][126].
In the gut, the beneficial microbes metabolize the prebiotics, resulting in the generation of SCFAs (namely, acetate, propionate, butyrate) that are involved in neuromodulation, in anti-inflammatory processes, in the regulation of both intestinal and blood-brain barriers [127][128].
Like probiotics, prebiotics also play a beneficial role in managing neurological and neurodegenerative diseases [129]. For instance, lactulose and melibiose improve short-term memory and cognitive ability in AD mice [130]; bimuno-GOS ameliorate anti-social behavior in children with ASD [131]; oral administration of Marinda officinalis-derived oligosaccharides ameliorates memory and learning ability, decreases plaque formation, oxidative stress, and inflammation in both rats and mice AD models [132][133].
Concerning PD, to date, few studies have been conducted to evaluate the effects of prebiotics on PD animal models and patients (Table 1) [112][134][135][136][137][138]. In a mouse model of PD, Perez–Pardo et al. found that prebiotic fibers (FOS, GOS and nutriose, a soluble corn fibre) can normalize motor symptoms, reduce α-synuclein levels, and restore GI dysfunction, inflammation and dopamine transporter expression [135]; further, it has been shown that the prebiotic polymannuronic acid can prevent dopaminergic neuronal loss via SCFAs-mediated anti-inflammatory and anti-apoptotic mechanisms [136]. In addition, another study, performed by using 6-OHDA PD rat model, reported that the supplementation with the medium obtained from the probiotic L. salivarius subsp. salicinium AP-32 culture can reduce dopaminergic neuronal loss, motor dysfunctions, muscle atrophy, oxidative stress (increased SOD and GPx) and inflammation [134][139]. Interestingly, another study highlighted a raise in BDNF levels in the hippocampus of rats after the administration of FOS and GOS [140]. Since BDNF is involved in neuronal protection, survival, growth, and in synaptic plasticity [141], this finding suggests that prebiotics supplementation might have a role on brain neuroprotection. Finally, some studies performed in PD animal models report the beneficial effects of sodium butyrate in improving PD symptoms [142][143]; therefore, butyrogenic prebiotics could be used to increase butyrate concentration in the colon and help to manage PD [127].
In patients, two studies reported the effects of insoluble fibers on constipation. Indeed, both Astarloa et al., by administering wheat, pectin, and dimethylpolyoxyhexane-900, and Ashraf et al., by using psyllium, found a significant improvement in constipation [137][138]. Finally, another study investigated the effects of an oral supplementation with resistant starch, whose fermentation by anaerobic bacteria leads to the production of SCFAs, finding an increased butyrate concentration, as well as an improvement in non-motor symptoms [112].
In conclusion, despite few studies on PD, the satisfactory clinical outcomes on patients, especially on constipation, suggest that prebiotics might be a possible adjuvant therapy for PD, although more human clinical trials are mandatory to support this conclusion.

4. Gut Microbiota-Based PD Interventions: Diet

Although multifactorial interactions are involved in the prevalence and incidence of neurodegenerative diseases, nutrition plays an essential role in the pathogenesis and development of neurodegenerative diseases such as AD and PD [144][145]. Recent findings have revealed that diet, as a non-pharmacological element, plays an important role not only as a risk factor but also as a potential therapeutic approach for treating PD (Table 2) [105][146][147][148][149][150][151][152][153][154][155][156][157][158][159][160][161]. The effects of diet intervention on PD development can be attributed to different mechanisms. First, by altering intestinal microbiota composition and consequently affecting the gut-brain axis or by directly interfering with immune cells. As a matter of fact, diet is probably the most influential factor in determining the structure and metabolic function of the intestinal microbiota. Moreover, dietary components might also modulate the chronic inflammatory response that is associated with aging. Intriguingly, diet components can reduce constipation and improve L-dopa uptake, which is the first-line therapy for PD [162][163]. Therefore, consuming a constant diet on a long-term basis can impact the development of PD; however, it is still to be elucidated as to how a particular diet reduces the risk of this development. Here, the researchers discuss how changes in diet may prevent or modify PD progression, with a special focus on Mediterranean, ketogenic, and omega-3-rich diets.
Table 2. The effects of dietary interventions in PD clinical trials.

5. Gut Microbiota-Based PD Interventions: Fecal Microbiota Transplantation

Fecal microbiota transplantation (FMT) consists in the transfer of resuspended and filtered stool material from a healthy donor to a patient’s gut. The aim of this approach is to counteract dysbiosis while favoring the establishment of a beneficial and balanced microbiota [164][165]. Although colonoscopy is the preferred method of transplantation, delivery through nasogastric or nasojejunal tube, enema, or orally administered capsules have also been tested [164][166]. Following the successful use of FMT in the treatment of refractory or recurrent Clostridium difficile infection, several studies have been conducted to explore FMT as a therapeutic strategy for a wide range of neurological disorders, including multiple sclerosis, epilepsy, ASD, Tourette syndrome, diabetic neuropathy, AD and PD, with promising preclinical and clinical data [167][168][169][170][171]. Concerning PD, consistent preclinical studies and a handful of human case reports have shown that FMT might be exploited to reduce motor and non-motor symptoms, as well as constipation, at least in the short term [168][172][173][174][175][176][177][178][179][180][181] (Table 3). Early evidence came in 2016 from the work of Sampson et al., who first reported that the transfer of fecal matter from human PD patients to α-synuclein overexpressing mice substantially worsened their physical symptoms in comparison with mice receiving feces from healthy human donors [172]. These results were then confirmed in 2018, when Sun et al. showed that fecal microbiota transfer from PD mice to their healthy counterpart increases motor deficits while reducing the striatal levels of the neurotransmitters dopamine, serotonin and their metabolites, thus reproducing the typical features of the disease [173]. Conversely, fecal matter transplantation from healthy mice to PD recipient mice improved physical performance, ameliorated motor symptoms and reduced dysbiosis in several independent studies [173][174][175][176]. Looking at the GM composition, there is evidence that FMT re-establishes eubiosis by disadvantaging the growth of Desulfovibrio, Akkermansia and Proteobacteria (orders Enterobacteriales and Turicibacteriales), while simultaneously favoring the proliferation of beneficial bacteria such as Bacteroidetes and Actinobacteria phyla, with a particular effect on Blautia and Prevotella species [173][174][176]. Moreover, FMT appears to protect from gut inflammation by promoting intestinal barrier integrity and reducing the levels of LPS in the colon, serum, and SN, therefore preventing leaky gut and systemic inflammation [174]. At the brain level, FMT contrasts cognitive damage by decreasing α-synuclein expression and restoring the optimal levels of the striatal neurotransmitters dopamine and serotonin, thus supporting neuroprotection [173][175][177]. Notably, decreased neuroinflammation following FMT has been reported by numerous preclinical studies [173][174][175][176]. This beneficial effect should be ascribed to the ability of GM to modulate microglia and astrocyte activation in SN by regulating the TLR4/NF-κB pro-inflammatory pathway and reducing the expression of GSK3β, iNOS and IL-1β, which are implicated in PD pathogenesis and progression [173][174][175][176][182][183][184].
Table 3. Preclinical and clinical studies on the use of fecal microbiota transplantation for Parkinson’s disease.
Nevertheless, FMT studies involving humans are still limited. One case study conducted in 2019 by Huang et al. investigated the potential therapeutic benefit of FMT in a 71-year-old male PD patient reporting constipation (>3 years) and motor symptoms (for 7 years). While FMT successfully promoted regular defecation, tremor disappeared only temporarily and then reappeared two months after transplant [178]. Three subsequent studies involving 6, 11 and 15 PD patients, respectively, confirmed the reduction in constipation, as well as in motor and non-motor symptoms following FMT, as indicated by the decreased scores registered in various PD assessment tests [179][180][181].
On the whole, from a clinical point of view, better and longer-term outcomes were obtained using colonoscopy compared to nasointestinal delivery [180]. In line with preclinical data, PD patients undergoing FMT showed an increased presence of Blautia and Prevotella and a diminished overall abundance of Bacteroidetes, thus confirming the efficacy of this approach in modifying the GM composition [179].
Despite the therapeutic potential of FMT for the treatment of PD, several limitations still exist and need to be addressed. Standard clinical protocols, delivery methods, periodicity, donor’s selection criteria, patient’s inclusion criteria, long-term benefits and potential risks remain an issue [165][170][185][186][187][188][189]. Within this context, 6 cases of adverse events occurred in human studies: flatulence (1), diarrhea (2), hospitalization under observation (1) and GI pain (2) [180][181]. Therefore, although not life-threatening, the nature of these complications should be better investigated.
In addition, randomized controlled trials involving a considerable number of patients are required to better assess feasibility, therapeutic efficacy, safety and long-term benefits of this promising GM-modifying approach [190].

References

  1. Rothstein, J.D.; Patel, S.; Regan, M.R.; Haenggeli, C.; Huang, Y.H.; Bergles, D.E.; Jin, L.; Dykes Hoberg, M.; Vidensky, S.; Chung, D.S.; et al. β-Lactam Antibiotics Offer Neuroprotection by Increasing Glutamate Transporter Expression. Nature 2005, 433, 73–77.
  2. Lipski, J.; Wan, C.K.; Bai, J.Z.; Pi, R.; Li, D.; Donnelly, D. Neuroprotective Potential of Ceftriaxone in in Vitro Models of Stroke. Neuroscience 2007, 146, 617–629.
  3. Burton, A. Antibiotics for Neurological Ailments? Lancet Neurol. 2005, 4, 142.
  4. Pradhan, S.; Madke, B.; Kabra, P.; Singh, A. Anti-Inflammatory and Immunomodulatory Effects of Antibiotics and Their Use in Dermatology. Indian J. Dermatol. 2016, 61, 469.
  5. Stoilova, T.; Colombo, L.; Forloni, G.; Tagliavini, F.; Salmona, M. A New Face for Old Antibiotics: Tetracyclines in Treatment of Amyloidoses. J. Med. Chem. 2013, 56, 5987–6006.
  6. Van Vuuren, M.J.; Nell, T.A.; Carr, J.A.; Kell, D.B.; Pretorius, E. Iron Dysregulation and Inflammagens Related to Oral and Gut Health Are Central to the Development of Parkinson’s Disease. Biomolecules 2020, 11, 30.
  7. Bortolanza, M.; Nascimento, G.C.; Socias, S.B.; Ploper, D.; Chehín, R.N.; Raisman-Vozari, R.; Del-Bel, E. Tetracycline Repurposing in Neurodegeneration: Focus on Parkinson’s Disease. J. Neural. Transm. 2018, 125, 1403–1415.
  8. Yadav, N.; Thakur, A.K.; Shekhar, N. Ayushi Potential of Antibiotics for the Treatment and Management of Parkinson’s Disease: An Overview. Curr. Drug Res. Rev. 2021, 13, 166–171.
  9. Hurkacz, M.; Dobrek, L.; Wiela-Hojeńska, A. Antibiotics and the Nervous System—Which Face of Antibiotic Therapy Is Real, Dr. Jekyll (Neurotoxicity) or Mr. Hyde (Neuroprotection)? Molecules 2021, 26, 7456.
  10. Balducci, C.; Forloni, G. Doxycycline for Alzheimer’s Disease: Fighting β-Amyloid Oligomers and Neuroinflammation. Front. Pharmacol. 2019, 10, 738.
  11. Lorente-Picón, M.; Laguna, A. New Avenues for Parkinson’s Disease Therapeutics: Disease-Modifying Strategies Based on the Gut Microbiota. Biomolecules 2021, 11, 433.
  12. Pu, Y.; Chang, L.; Qu, Y.; Wang, S.; Zhang, K.; Hashimoto, K. Antibiotic-Induced Microbiome Depletion Protects against MPTP-Induced Dopaminergic Neurotoxicity in the Brain. Aging 2019, 11, 6915–6929.
  13. Koutzoumis, D.N.; Vergara, M.; Pino, J.; Buddendorff, J.; Khoshbouei, H.; Mandel, R.J.; Torres, G.E. Alterations of the Gut Microbiota with Antibiotics Protects Dopamine Neuron Loss and Improve Motor Deficits in a Pharmacological Rodent Model of Parkinson’s Disease. Exp. Neurol. 2020, 325, 113159.
  14. Cui, C.; Hong, H.; Shi, Y.; Zhou, Y.; Qiao, C.-M.; Zhao, W.-J.; Zhao, L.-P.; Wu, J.; Quan, W.; Niu, G.-Y.; et al. Vancomycin Pretreatment on MPTP-Induced Parkinson’s Disease Mice Exerts Neuroprotection by Suppressing Inflammation Both in Brain and Gut. J. Neuroimmune Pharmacol. 2022.
  15. Baizabal-Carvallo, J.F.; Alonso-Juarez, M.; Fekete, R. Intestinal Decontamination Therapy for Dyskinesia and Motor Fluctuations in Parkinson’s Disease. Front. Neurol. 2021, 12, 729961.
  16. Dănău, A.; Dumitrescu, L.; Lefter, A.; Tulbă, D.; Popescu, B.O. Small Intestinal Bacterial Overgrowth as Potential Therapeutic Target in Parkinson’s Disease. Int. J. Mol. Sci. 2021, 22, 11663.
  17. Ramprasad, C.; Douglas, J.Y.; Moshiree, B. Parkinson’s Disease and Current Treatments for Its Gastrointestinal Neurogastromotility Effects. Curr. Treat Options Gastroenterol 2018, 16, 489–510.
  18. Fasano, A.; Bove, F.; Gabrielli, M.; Petracca, M.; Zocco, M.A.; Ragazzoni, E.; Barbaro, F.; Piano, C.; Fortuna, S.; Tortora, A.; et al. The Role of Small Intestinal Bacterial Overgrowth in Parkinson’s Disease. Mov. Disord. 2013, 28, 1241–1249.
  19. Pekary, A.E.; Sattin, A. Rifaximin Modulates TRH and TRH-like Peptide Expression throughout the Brain and Peripheral Tissues of Male Rats. BMC Neurosci. 2022, 23, 9.
  20. DiBaise, J.K.; Crowell, M.D.; Driver-Dunckley, E.; Mehta, S.H.; Hoffman-Snyder, C.; Lin, T.; Adler, C.H. Weight Loss in Parkinson’s Disease: No Evidence for Role of Small Intestinal Bacterial Overgrowth. J. Park. Dis. 2018, 8, 571–581.
  21. Yimer, E.M.; Hishe, H.Z.; Tuem, K.B. Repurposing of the β-Lactam Antibiotic, Ceftriaxone for Neurological Disorders: A Review. Front. Neurosci. 2019, 13, 236.
  22. Tai, C.-H.; Bellesi, M.; Chen, A.-C.; Lin, C.-L.; Li, H.-H.; Lin, P.-J.; Liao, W.-C.; Hung, C.-S.; Schwarting, R.K.; Ho, Y.-J. A New Avenue for Treating Neuronal Diseases: Ceftriaxone, an Old Antibiotic Demonstrating Behavioral Neuronal Effects. Behavioural. Brain Res. 2019, 364, 149–156.
  23. Yamada, J.; Jinno, S. Alterations in Neuronal Survival and Glial Reactions after Axotomy by Ceftriaxone and Minocycline in the Mouse Hypoglossal Nucleus. Neurosci. Lett. 2011, 504, 295–300.
  24. Zhang, Y.; Zhang, X.; Qu, S. Ceftriaxone Protects Astrocytes from MPP+ via Suppression of NF-ΚB/JNK/c-Jun Signaling. Mol. Neurobiol. 2015, 52, 78–92.
  25. Ren, C.; He, K.-J.; Hu, H.; Zhang, J.-B.; Dong, L.-G.; Li, D.; Chen, J.; Mao, C.-J.; Wang, F.; Liu, C.-F. Induction of Parkinsonian-Like Changes via Targeted Downregulation of Astrocytic Glutamate Transporter GLT-1 in the Striatum. J. Park. Dis. 2022, 12, 295–314.
  26. Ruzza, P.; Siligardi, G.; Hussain, R.; Marchiani, A.; Islami, M.; Bubacco, L.; Delogu, G.; Fabbri, D.; Dettori, M.A.; Sechi, M.; et al. Ceftriaxone Blocks the Polymerization of α-Synuclein and Exerts Neuroprotective Effects in Vitro. ACS Chem. Neurosci. 2014, 5, 30–38.
  27. Smaga, I.; Fierro, D.; Mesa, J.; Filip, M.; Knackstedt, L.A. Molecular Changes Evoked by the Beta-Lactam Antibiotic Ceftriaxone across Rodent Models of Substance Use Disorder and Neurological Disease. Neurosci. Biobehav. Rev. 2020, 115, 116–130.
  28. Zhou, X.; Lu, J.; Wei, K.; Wei, J.; Tian, P.; Yue, M.; Wang, Y.; Hong, D.; Li, F.; Wang, B.; et al. Neuroprotective Effect of Ceftriaxone on MPTP-Induced Parkinson’s Disease Mouse Model by Regulating Inflammation and Intestinal Microbiota. Oxid Med. Cell. Longev. 2021, 2021, 9424582.
  29. Kaur, B.; Prakash, A. Ceftriaxone Attenuates Glutamate-Mediated Neuro-Inflammation and Restores BDNF in MPTP Model of Parkinson’s Disease in Rats. Pathophysiology 2017, 24, 71–79.
  30. Bisht, R.; Kaur, B.; Gupta, H.; Prakash, A. Ceftriaxone Mediated Rescue of Nigral Oxidative Damage and Motor Deficits in MPTP Model of Parkinson’s Disease in Rats. Neurotoxicology 2014, 44, 71–79.
  31. Brahmachari, S. Induction of Glial Fibrillary Acidic Protein Expression in Astrocytes by Nitric Oxide. J. Neurosci. 2006, 26, 4930–4939.
  32. Jurga, A.M.; Paleczna, M.; Kuter, K.Z. Overview of General and Discriminating Markers of Differential Microglia Phenotypes. Front. Cell. Neurosci. 2020, 14, 198.
  33. Ho, S.-C.; Hsu, C.-C.; Pawlak, C.R.; Tikhonova, M.A.; Lai, T.-J.; Amstislavskaya, T.G.; Ho, Y.-J. Effects of Ceftriaxone on the Behavioral and Neuronal Changes in an MPTP-Induced Parkinson’s Disease Rat Model. Behavioural. Brain Res. 2014, 268, 177–184.
  34. Hsu, C.-Y.; Hung, C.-S.; Chang, H.-M.; Liao, W.-C.; Ho, S.-C.; Ho, Y.-J. Ceftriaxone Prevents and Reverses Behavioral and Neuronal Deficits in an MPTP-Induced Animal Model of Parkinson’s Disease Dementia. Neuropharmacology 2015, 91, 43–56.
  35. Hsieh, M.-H.; Meng, W.-Y.; Liao, W.-C.; Weng, J.-C.; Li, H.-H.; Su, H.-L.; Lin, C.-L.; Hung, C.-S.; Ho, Y.-J. Ceftriaxone Reverses Deficits of Behavior and Neurogenesis in an MPTP-Induced Rat Model of Parkinson’s Disease Dementia. Brain Res. Bull 2017, 132, 129–138.
  36. Chotibut, T.; Davis, R.W.; Arnold, J.C.; Frenchek, Z.; Gurwara, S.; Bondada, V.; Geddes, J.W.; Salvatore, M.F. Ceftriaxone Increases Glutamate Uptake and Reduces Striatal Tyrosine Hydroxylase Loss in 6-OHDA Parkinson’s Model. Mol. Neurobiol. 2014, 49, 1282–1292.
  37. Weng, J.-C.; Tikhonova, M.A.; Chen, J.-H.; Shen, M.-S.; Meng, W.-Y.; Chang, Y.-T.; Chen, K.-H.; Liang, K.-C.; Hung, C.-S.; Amstislavskaya, T.G.; et al. Ceftriaxone Prevents the Neurodegeneration and Decreased Neurogenesis Seen in a Parkinson’s Disease Rat Model: An Immunohistochemical and MRI Study. Behav. Brain Res. 2016, 305, 126–139.
  38. Leung, T.C.H.; Lui, C.N.P.; Chen, L.W.; Yung, W.H.; Chan, Y.S.; Yung, K.K.L. Ceftriaxone Ameliorates Motor Deficits and Protects Dopaminergic Neurons in 6-Hydroxydopamine-Lesioned Rats. ACS Chem. Neurosci. 2012, 3, 22–30.
  39. Kelsey, J.E.; Neville, C. The Effects of the β-Lactam Antibiotic, Ceftriaxone, on Forepaw Stepping and l-DOPA-Induced Dyskinesia in a Rodent Model of Parkinson’s Disease. Psychopharmacology 2014, 231, 2405–2415.
  40. Chotibut, T.; Meadows, S.; Kasanga, E.A.; McInnis, T.; Cantu, M.A.; Bishop, C.; Salvatore, M.F. Ceftriaxone Reduces L-Dopa-Induced Dyskinesia Severity in 6-Hydroxydopamine Parkinson’s Disease Model. Mov. Disord. 2017, 32, 1547–1556.
  41. Karaman, I.; Kizilay-Ozfidan, G.; Karadag, C.H.; Ulugol, A. Lack of Effect of Ceftriaxone, a GLT-1 Transporter Activator, on Spatial Memory in Mice. Pharmacol. Biochem. Behav. 2013, 108, 61–65.
  42. Huang, C.-K.; Chang, Y.-T.; Amstislavskaya, T.G.; Tikhonova, M.A.; Lin, C.-L.; Hung, C.-S.; Lai, T.-J.; Ho, Y.-J. Synergistic Effects of Ceftriaxone and Erythropoietin on Neuronal and Behavioral Deficits in an MPTP-Induced Animal Model of Parkinson’s Disease Dementia. Behav. Brain Res. 2015, 294, 198–207.
  43. Garrido-Mesa, N.; Zarzuelo, A.; Gálvez, J. Minocycline: Far beyond an Antibiotic. Br. J. Pharmacol. 2013, 169, 337–352.
  44. Cankaya, S.; Cankaya, B.; Kilic, U.; Kilic, E.; Yulug, B. The Therapeutic Role of Minocycline in Parkinson’s Disease. Drugs Context 2019, 8, 212553.
  45. Peng, J.; Xie, L.; Stevenson, F.F.; Melov, S.; di Monte, D.A.; Andersen, J.K. Nigrostriatal Dopaminergic Neurodegeneration in the Weaver Mouse Is Mediated via Neuroinflammation and Alleviated by Minocycline Administration. J. Neurosci. 2006, 26, 11644–11651.
  46. Inamdar, A.A.; Chaudhuri, A.; O’Donnell, J. The Protective Effect of Minocycline in a Paraquat-Induced Parkinson’s Disease Model in Drosophila Is Modified in Altered Genetic Backgrounds. Park. Dis. 2012, 2012, 212553.
  47. Kim, H.-S.; Suh, Y.-H. Minocycline and Neurodegenerative Diseases. Behav. Brain Res. 2009, 196, 168–179.
  48. Thomas, M.; Le, W.D.; Jankovic, J. Minocycline and Other Tetracycline Derivatives: A Neuroprotective Strategy in Parkinson’s Disease and Huntington’s Disease. Clin. Neuropharmacol 2003, 26, 18–23.
  49. Yong, V.W.; Wells, J.; Giuliani, F.; Casha, S.; Power, C.; Metz, L.M. The Promise of Minocycline in Neurology. Lancet Neurol. 2004, 3, 744–751.
  50. Fan, L.; Wang, T.-L.; Xu, Y.C.; Ma, Y.H.; Ye, W.G. Minocycline May Be Useful to Prevent/Treat Postoperative Cognitive Decline in Elderly Patients. Med. Hypotheses 2011, 76, 733–736.
  51. Blum, D.; Chtarto, A.; Tenenbaum, L.; Brotchi, J.; Levivier, M. Clinical Potential of Minocycline for Neurodegenerative Disorders. Neurobiol. Dis. 2004, 17, 359–366.
  52. Thomas, M.; Le, W. Minocycline: Neuroprotective Mechanisms in Parkinsons Disease. Curr. Pharm. Des. 2004, 10, 679–686.
  53. Zemke, D.; Majid, A. The Potential of Minocycline for Neuroprotection in Human Neurologic Disease. Clin. Neuropharmacol 2004, 27, 293–298.
  54. Ruan, Z.; Zhang, D.; Huang, R.; Sun, W.; Hou, L.; Zhao, J.; Wang, Q. Microglial Activation Damages Dopaminergic Neurons through MMP-2/-9-Mediated Increase of Blood-Brain Barrier Permeability in a Parkinson’s Disease Mouse Model. Int. J. Mol. Sci. 2022, 23, 2793.
  55. Wang, Y.; Wang, Q.; Yu, R.; Zhang, Q.; Zhang, Z.; Li, H.; Ren, C.; Yang, R.; Niu, H. Minocycline Inhibition of Microglial Rescues Nigrostriatal Dopaminergic Neurodegeneration Caused by Mutant Alpha-Synuclein Overexpression. Aging 2020, 12, 14232–14243.
  56. Zhang, D.; Li, S.; Hou, L.; Jing, L.; Ruan, Z.; Peng, B.; Zhang, X.; Hong, J.-S.; Zhao, J.; Wang, Q. Microglial Activation Contributes to Cognitive Impairments in Rotenone-Induced Mouse Parkinson’s Disease Model. J. Neuroinflamm. 2021, 18, 4.
  57. Tomás-Camardiel, M.; Rite, I.; Herrera, A.J.; de Pablos, R.M.; Cano, J.; Machado, A.; Venero, J.L. Minocycline Reduces the Lipopolysaccharide-Induced Inflammatory Reaction, Peroxynitrite-Mediated Nitration of Proteins, Disruption of the Blood–Brain Barrier, and Damage in the Nigral Dopaminergic System. Neurobiol. Dis. 2004, 16, 190–201.
  58. Wu, D.C.; Jackson-Lewis, V.; Vila, M.; Tieu, K.; Teismann, P.; Vadseth, C.; Choi, D.-K.; Ischiropoulos, H.; Przedborski, S. Blockade of Microglial Activation Is Neuroprotective in the 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine Mouse Model of Parkinson Disease. J. Neurosci. 2002, 22, 1763–1771.
  59. Kumar, V.; Singh, B.K.; Chauhan, A.K.; Singh, D.; Patel, D.K.; Singh, C. Minocycline Rescues from Zinc-Induced Nigrostriatal Dopaminergic Neurodegeneration: Biochemical and Molecular Interventions. Mol. Neurobiol. 2016, 53, 2761–2777.
  60. Du, Y.; Ma, Z.; Lin, S.; Dodel, R.C.; Gao, F.; Bales, K.R.; Triarhou, L.C.; Chernet, E.; Perry, K.W.; Nelson, D.L.G.; et al. Minocycline Prevents Nigrostriatal Dopaminergic Neurodegeneration in the MPTP Model of Parkinson’s Disease. Proc. Natl. Acad. Sci. USA 2001, 98, 14669–14674.
  61. Jiang, B.-P.; Le, L.; Xu, L.-J.; Xiao, P.-G. Minocycline Inhibits ICAD Degradation and the NF-ΚB Activation Induced by 6-OHDA in PC12 Cells. Brain Res. 2014, 1586, 1–11.
  62. Radad, K.; Moldzio, R.; Rausch, W.-D. Minocycline Protects Dopaminergic Neurons Against Long-Term Rotenone Toxicity. Can. J. Neurol. Sci. J. Can. Des Sci. Neurol. 2010, 37, 81–85.
  63. Lin, S.; Wei, X.; Xu, Y.; Yan, C.; Dodel, R.; Zhang, Y.; Liu, J.; Klaunig, J.E.; Farlow, M.; Du, Y. Minocycline Blocks 6-Hydroxydopamine-Induced Neurotoxicity and Free Radical Production in Rat Cerebellar Granule Neurons. Life Sci. 2003, 72, 1635–1641.
  64. Cronin, A.; Grealy, M. Neuroprotective and Neuro-Restorative Effects of Minocycline and Rasagiline in a Zebrafish 6-Hydroxydopamine Model of Parkinson’s Disease. Neuroscience 2017, 367, 34–46.
  65. Maneshian, M.; Nasirinezhad, F.; Mohammadi, F.; Behzadi, M.; Asadi-Shekaari, M.; Shabani, M. Minocycline Mitigation of Tremor Syndrome and Defect of Cognitive and Balance Induced by Harmaline. Basic Clin. Neurosci. J. 2021, 12, 255–268.
  66. Quintero, E.M.; Willis, L.; Singleton, R.; Harris, N.; Huang, P.; Bhat, N.; Granholm, A.-C. Behavioral and Morphological Effects of Minocycline in the 6-Hydroxydopamine Rat Model of Parkinson’s Disease. Brain Res. 2006, 1093, 198–207.
  67. Sun, C.; Wang, Y.; Mo, M.; Song, C.; Wang, X.; Chen, S.; Liu, Y. Minocycline Protects against Rotenone-Induced Neurotoxicity Correlating with Upregulation of Nurr1 in a Parkinson’s Disease Rat Model. Biomed Res. Int. 2019, 2019, 6843265.
  68. Huang, C.-L.; Lee, Y.-C.; Yang, Y.-C.; Kuo, T.-Y.; Huang, N.-K. Minocycline Prevents Paraquat-Induced Cell Death through Attenuating Endoplasmic Reticulum Stress and Mitochondrial Dysfunction. Toxicol. Lett. 2012, 209, 203–210.
  69. Fernandez-Gomez, F.J.; Galindo, M.F.; Gomez-Lazaro, M.; González-García, C.; Ceña, V.; Aguirre, N.; Jordán, J. Involvement of Mitochondrial Potential and Calcium Buffering Capacity in Minocycline Cytoprotective Actions. Neuroscience 2005, 133, 959–967.
  70. Dixit, A.; Srivastava, G.; Verma, D.; Mishra, M.; Singh, P.K.; Prakash, O.; Singh, M.P. Minocycline, Levodopa and MnTMPyP Induced Changes in the Mitochondrial Proteome Profile of MPTP and Maneb and Paraquat Mice Models of Parkinson’s Disease. Biochim. Et Biophys. Acta (BBA)-Mol. Basis Dis. 2013, 1832, 1227–1240.
  71. Yang, L.; Sugama, S.; Chirichigno, J.W.; Gregorio, J.; Lorenzl, S.; Shin, D.H.; Browne, S.E.; Shimizu, Y.; Joh, T.H.; Beal, M.F.; et al. Minocycline Enhances MPTP Toxicity to Dopaminergic Neurons. J. Neurosci. Res. 2003, 74, 278–285.
  72. Diguet, E.; Fernagut, P.-O.; Wei, X.; Du, Y.; Rouland, R.; Gross, C.; Bezard, E.; Tison, F. Deleterious Effects of Minocycline in Animal Models of Parkinson’s Disease and Huntington’s Disease. Eur. J. Neurosci. 2004, 19, 3266–3276.
  73. NINDS NET-PD Investigators. A Pilot Clinical Trial of Creatine and Minocycline in Early Parkinson Disease. Clin. Neuropharmacol 2008, 31, 141–150.
  74. NINDS NET-PD Investigators. A Randomized, Double-Blind, Futility Clinical Trial of Creatine and Minocycline in Early Parkinson Disease. Neurology 2006, 66, 664–671.
  75. Rahmani, M.; Negro Álvarez, S.E.; Hernández, E.B. The Potential Use of Tetracyclines in Neurodegenerative Diseases and the Role of Nano-Based Drug Delivery Systems. Eur. J. Pharm. Sci. 2022, 175, 106237.
  76. Santa-Cecília, F.V.; Socias, B.; Ouidja, M.O.; Sepulveda-Diaz, J.E.; Acuña, L.; Silva, R.L.; Michel, P.P.; Del-Bel, E.; Cunha, T.M.; Raisman-Vozari, R. Doxycycline Suppresses Microglial Activation by Inhibiting the P38 MAPK and NF-KB Signaling Pathways. Neurotox. Res. 2016, 29, 447–459.
  77. Cho, Y.; Son, H.J.; Kim, E.-M.; Choi, J.H.; Kim, S.T.; Ji, I.J.; Choi, D.H.; Joh, T.H.; Kim, Y.S.; Hwang, O. Doxycycline Is Neuroprotective Against Nigral Dopaminergic Degeneration by a Dual Mechanism Involving MMP-3. Neurotox. Res. 2009, 16, 361–371.
  78. Dominguez-Meijide, A.; Parrales, V.; Vasili, E.; González-Lizárraga, F.; König, A.; Lázaro, D.F.; Lannuzel, A.; Haik, S.; del Bel, E.; Chehín, R.; et al. Doxycycline Inhibits α-Synuclein-Associated Pathologies in Vitro and in Vivo. Neurobiol. Dis. 2021, 151, 105256.
  79. Do Amaral, L.; dos Santos, N.A.G.; Sisti, F.M.; del Bel, E.; Santos, A.C. dos The Antibiotic Doxycycline Mimics the NGF Signaling in PC12 Cells: A Relevant Mechanism for Neuroprotection. Chem. Biol. Interact 2021, 341, 109454.
  80. González-Lizárraga, F.; Socías, S.B.; Ávila, C.L.; Torres-Bugeau, C.M.; Barbosa, L.R.S.; Binolfi, A.; Sepúlveda-Díaz, J.E.; Del-Bel, E.; Fernandez, C.O.; Papy-Garcia, D.; et al. Repurposing Doxycycline for Synucleinopathies: Remodelling of α-Synuclein Oligomers towards Non-Toxic Parallel Beta-Sheet Structured Species. Sci. Rep. 2017, 7, 41755.
  81. Lazzarini, M.; Martin, S.; Mitkovski, M.; Vozari, R.R.; Stühmer, W.; Bel, E. del Doxycycline Restrains Glia and Confers Neuroprotection in a 6-OHDA Parkinson Model. Glia 2013, 61, 1084–1100.
  82. Zhang, G.-B.; Feng, Y.-H.; Wang, P.-Q.; Song, J.-H.; Wang, P.; Wang, S.-A. A Study on the Protective Role of Doxycycline upon Dopaminergic Neuron of LPS-PD Rat Model Rat. Eur. Rev. Med. Pharmacol. Sci. 2015, 19, 3468–3474.
  83. Bortolanza, M.; Nascimento, G.C.; Raisman-Vozari, R.; Del-Bel, E. Doxycycline and Its Derivative, COL-3, Decrease Dyskinesia Induced by L-DOPA in Hemiparkinsonian Rats. Br. J. Pharmacol. 2021, 178, 2595–2616.
  84. Bi, W.; Zhu, L.; Jing, X.; Liang, Y.; Tao, E. Rifampicin and Parkinson’s Disease. Neurol. Sci. 2013, 34, 137–141.
  85. Yulug, B.; Hanoglu, L.; Kilic, E.; Schabitz, W.R. Rifampicin: An Antibiotic with Brain Protective Function. Brain Res. Bull 2014, 107, 37–42.
  86. Lin, D.; Jing, X.; Chen, Y.; Liang, Y.; Lei, M.; Peng, S.; Zhou, T.; Zheng, D.; Zeng, Z.; Wu, X.; et al. Rifampicin Pre-Treatment Inhibits the Toxicity of Rotenone-Induced PC12 Cells by Enhancing Sumoylation Modification of α-Synuclein. Biochem. Biophys. Res. Commun. 2017, 485, 23–29.
  87. Li, J.; Zhu, M.; Rajamani, S.; Uversky, V.N.; Fink, A.L. Rifampicin Inhibits α-Synuclein Fibrillation and Disaggregates Fibrils. Chem. Biol. 2004, 11, 1513–1521.
  88. Xu, J.; Wei, C.; Xu, C.; Bennett, M.C.; Zhang, G.; Li, F.; Tao, E. Rifampicin Protects PC12 Cells against MPP+-Induced Apoptosis and Inhibits the Expression of an α-Synuclein Multimer. Brain Res. 2007, 1139, 220–225.
  89. Liang, Y.; Zhou, T.; Chen, Y.; Lin, D.; Jing, X.; Peng, S.; Zheng, D.; Zeng, Z.; Lei, M.; Wu, X.; et al. Rifampicin Inhibits Rotenone-Induced Microglial Inflammation via Enhancement of Autophagy. Neurotoxicology 2017, 63, 137–145.
  90. Acuña, L.; Hamadat, S.; Corbalán, N.S.; González-Lizárraga, F.; Dos-Santos-Pereira, M.; Rocca, J.; Díaz, J.S.; Del-Bel, E.; Papy-García, D.; Chehín, R.N.; et al. Rifampicin and Its Derivative Rifampicin Quinone Reduce Microglial Inflammatory Responses and Neurodegeneration Induced In Vitro by α-Synuclein Fibrillary Aggregates. Cells 2019, 8, 776.
  91. Liang, Y.; Zheng, D.; Peng, S.; Lin, D.; Jing, X.; Zeng, Z.; Chen, Y.; Huang, K.; Xie, Y.; Zhou, T.; et al. Rifampicin Attenuates Rotenone-Treated Microglia Inflammation via Improving Lysosomal Function. Toxicol. Vitr. 2020, 63, 104690.
  92. Wu, X.; Liang, Y.; Jing, X.; Lin, D.; Chen, Y.; Zhou, T.; Peng, S.; Zheng, D.; Zeng, Z.; Lei, M.; et al. Rifampicin Prevents SH-SY5Y Cells from Rotenone-Induced Apoptosis via the PI3K/Akt/GSK-3β/CREB Signaling Pathway. Neurochem. Res. 2018, 43, 886–893.
  93. Jing, X.; Shi, Q.; Bi, W.; Zeng, Z.; Liang, Y.; Wu, X.; Xiao, S.; Liu, J.; Yang, L.; Tao, E. Rifampicin Protects PC12 Cells from Rotenone-Induced Cytotoxicity by Activating GRP78 via PERK-EIF2α-ATF4 Pathway. PLoS ONE 2014, 9, e92110.
  94. Oida, Y.; Kitaichi, K.; Nakayama, H.; Ito, Y.; Fujimoto, Y.; Shimazawa, M.; Nagai, H.; Hara, H. Rifampicin Attenuates the MPTP-Induced Neurotoxicity in Mouse Brain. Brain Res. 2006, 1082, 196–204.
  95. Yurtsever, İ.; Üstündağ, Ü.V.; Ünal, İ.; Ateş, P.S.; Emekli-Alturfan, E. Rifampicin Decreases Neuroinflammation to Maintain Mitochondrial Function and Calcium Homeostasis in Rotenone-Treated Zebrafish. Drug Chem. Toxicol. 2022, 45, 1544–1551.
  96. Modi, S.R.; Collins, J.J.; Relman, D.A. Antibiotics and the Gut Microbiota. J. Clin. Investig. 2014, 124, 4212–4218.
  97. Markulin, I.; Matasin, M.; Turk, V.E.; Salković-Petrisic, M. Challenges of Repurposing Tetracyclines for the Treatment of Alzheimer’s and Parkinson’s Disease. J. Neural. Transm. 2022, 129, 773–804.
  98. 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.
  99. Ternák, G.; Kuti, D.; Kovács, K.J. Dysbiosis in Parkinson’s Disease Might Be Triggered by Certain Antibiotics. Med. Hypotheses 2020, 137, 109564.
  100. Wang, C.; Lau, C.Y.; Ma, F.; Zheng, C. Genome-Wide Screen Identifies Curli Amyloid Fibril as a Bacterial Component Promoting Host Neurodegeneration. Proc. Natl. Acad. Sci. USA 2021, 118, e2106504118.
  101. Roe, K. An Alternative Explanation for Alzheimer’s Disease and Parkinson’s Disease Initiation from Specific Antibiotics, Gut Microbiota Dysbiosis and Neurotoxins. Neurochem. Res. 2022, 47, 517–530.
  102. Mertsalmi, T.H.; Pekkonen, E.; Scheperjans, F. Antibiotic Exposure and Risk of Parkinson’s Disease in Finland: A Nationwide Case-Control Study. Mov. Disord. 2020, 35, 431–442.
  103. Palacios, N.; O’Reilly, É.J.; Schwarzschild, M.A.; Ascherio, A. Long-Term Use of Antibiotics and Risk of Parkinson’s Disease in the Nurses’ Health Study. Park. Dis. 2020, 2020, 4038375.
  104. Morelli, L.; Capurso, L. FAO/WHO Guidelines on Probiotics. J. Clin. Gastroenterol. 2012, 46, S1–S2.
  105. Alfonsetti, M.; Castelli, V.; d’Angelo, M. Are We What We Eat? Impact of Diet on the Gut–Brain Axis in Parkinson’s Disease. Nutrients 2022, 14, 380.
  106. Cristofori, F.; Dargenio, V.N.; Dargenio, C.; Miniello, V.L.; Barone, M.; Francavilla, R. Anti-Inflammatory and Immunomodulatory Effects of Probiotics in Gut Inflammation: A Door to the Body. Front. Immunol. 2021, 12, 578386.
  107. Gazerani, P. Probiotics for Parkinson’s Disease. Int. J. Mol. Sci. 2019, 20, 4121.
  108. Gupta, V.; Garg, R. PROBIOTICS. Indian J. Med. Microbiol. 2009, 27, 202–209.
  109. Reid, G.; Younes, J.A.; van der Mei, H.C.; Gloor, G.B.; Knight, R.; Busscher, H.J. Microbiota Restoration: Natural and Supplemented Recovery of Human Microbial Communities. Nat. Rev. Microbiol. 2011, 9, 27–38.
  110. Nandwana, V.; Nandwana, N.K.; Das, Y.; Saito, M.; Panda, T.; Das, S.; Almaguel, F.; Hosmane, N.S.; Das, B.C. The Role of Microbiome in Brain Development and Neurodegenerative Diseases. Molecules 2022, 27, 3402.
  111. Peterson, C.T. Dysfunction of the Microbiota-Gut-Brain Axis in Neurodegenerative Disease: The Promise of Therapeutic Modulation With Prebiotics, Medicinal Herbs, Probiotics, and Synbiotics. J. Evid Based Integr. Med. 2020, 25, 2515690X20957225.
  112. Becker, A.; Pierre Schmartz, G.; Gröger, L.; Grammes, N.; Galata, V.; Philippeit, H.; Weiland, J.; Ludwig, N.; Meese, E.; Tierling, S.; et al. Effects of Resistant Starch on Symptoms, Fecal Markers and Gut Microbiota in Parkinson’s Disease–the RESISTA-PD Trial. Genom. Proteom. Bioinform. 2021.
  113. Jiang, J.; Chu, C.; Wu, C.; Wang, C.; Zhang, C.; Li, T.; Zhai, Q.; Yu, L.; Tian, F.; Chen, W. Efficacy of Probiotics in Multiple Sclerosis: A Systematic Review of Preclinical Trials and Meta-Analysis of Randomized Controlled Trials. Food Funct. 2021, 12, 2354–2377.
  114. Mirzaei, H.; Sedighi, S.; Kouchaki, E.; Barati, E.; Dadgostar, E.; Aschner, M.; Tamtaji, O.R. Probiotics and the Treatment of Parkinson’s Disease: An Update. Cell. Mol. Neurobiol. 2021.
  115. Socała, K.; Doboszewska, U.; Szopa, A.; Serefko, A.; Włodarczyk, M.; Zielińska, A.; Poleszak, E.; Fichna, J.; Wlaź, P. The Role of Microbiota-Gut-Brain Axis in Neuropsychiatric and Neurological Disorders. Pharmacol. Res. 2021, 172, 105840.
  116. Xiang, S.; Ji, J.-L.; Li, S.; Cao, X.-P.; Xu, W.; Tan, L.; Tan, C.-C. Efficacy and Safety of Probiotics for the Treatment of Alzheimer’s Disease, Mild Cognitive Impairment, and Parkinson’s Disease: A Systematic Review and Meta-Analysis. Front. Aging Neurosci. 2022, 14.
  117. Hsiao, E.Y.; McBride, S.W.; Hsien, S.; Sharon, G.; Hyde, E.R.; McCue, T.; Codelli, J.A.; Chow, J.; Reisman, S.E.; Petrosino, J.F.; et al. Microbiota Modulate Behavioral and Physiological Abnormalities Associated with Neurodevelopmental Disorders. Cell 2013, 155, 1451–1463.
  118. Bonfili, L.; Cecarini, V.; Berardi, S.; Scarpona, S.; Suchodolski, J.S.; Nasuti, C.; Fiorini, D.; Boarelli, M.C.; Rossi, G.; Eleuteri, A.M. Microbiota Modulation Counteracts Alzheimer’s Disease Progression Influencing Neuronal Proteolysis and Gut Hormones Plasma Levels. Sci. Rep. 2017, 7, 2426.
  119. Akbari, E.; Asemi, Z.; Daneshvar Kakhaki, R.; Bahmani, F.; Kouchaki, E.; Tamtaji, O.R.; Hamidi, G.A.; Salami, M. Effect of Probiotic Supplementation on Cognitive Function and Metabolic Status in Alzheimer’s Disease: A Randomized, Double-Blind and Controlled Trial. Front. Aging Neurosci. 2016, 8, 256.
  120. Gibson, G.R.; Hutkins, R.; Sanders, M.E.; Prescott, S.L.; Reimer, R.A.; Salminen, S.J.; Scott, K.; Stanton, C.; Swanson, K.S.; Cani, P.D.; et al. Expert Consensus Document: The International Scientific Association for Probiotics and Prebiotics (ISAPP) Consensus Statement on the Definition and Scope of Prebiotics. Nat. Rev. Gastroenterol. Hepatol. 2017, 14, 491–502.
  121. Pandey, K.R.; Naik, S.R.; Vakil, B.V. Probiotics, Prebiotics and Synbiotics- a Review. J. Food Sci. Technol. 2015, 52, 7577–7587.
  122. Wang, Q.; Luo, Y.; Ray Chaudhuri, K.; Reynolds, R.; Tan, E.-K.; Pettersson, S. The Role of Gut Dysbiosis in Parkinson’s Disease: Mechanistic Insights and Therapeutic Options. Brain 2021, 144, 2571–2593.
  123. Wiciński, M.; Gębalski, J.; Mazurek, E.; Podhorecka, M.; Śniegocki, M.; Szychta, P.; Sawicka, E.; Malinowski, B. The Influence of Polyphenol Compounds on Human Gastrointestinal Tract Microbiota. Nutrients 2020, 12, 350.
  124. de Vrese, M.; Schrezenmeir, J. Probiotics, Prebiotics, and Synbiotics. Adv. Biochem. Eng. Biotechnol. 2008, 111, 1–66.
  125. Manzoor, S.; Wani, S.M.; Ahmad Mir, S.; Rizwan, D. Role of Probiotics and Prebiotics in Mitigation of Different Diseases. Nutrition 2022, 96, 111602.
  126. Raval, U.; Harary, J.M.; Zeng, E.; Pasinetti, G.M. The Dichotomous Role of the Gut Microbiome in Exacerbating and Ameliorating Neurodegenerative Disorders. Expert Rev. Neurother. 2020, 20, 673–686.
  127. Cantu-Jungles, T.M.; Rasmussen, H.E.; Hamaker, B.R. Potential of Prebiotic Butyrogenic Fibers in Parkinson’s Disease. Front. Neurol. 2019, 10, 663.
  128. Guo, T.; Chen, L. Gut Microbiota and Inflammation in Parkinson’s Disease: Pathogenetic and Therapeutic Insights. Eur. J. Inflamm. 2022, 20.
  129. Yang, H.; Liu, Y.; Cai, R.; Li, Y.; Gu, B. A Narrative Review of Relationship between Gut Microbiota and Neuropsychiatric Disorders: Mechanisms and Clinical Application of Probiotics and Prebiotics. Ann. Palliat. Med. 2021, 10, 2304–2313.
  130. Lee, Y.-S.; Lai, D.-M.; Huang, H.-J.; Lee-Chen, G.-J.; Chang, C.-H.; Hsieh-Li, H.M.; Lee, G.-C. Prebiotic Lactulose Ameliorates the Cognitive Deficit in Alzheimer’s Disease Mouse Model through Macroautophagy and Chaperone-Mediated Autophagy Pathways. J. Agric. Food Chem. 2021, 69, 2422–2437.
  131. Grimaldi, R.; Gibson, G.R.; Vulevic, J.; Giallourou, N.; Castro-Mejía, J.L.; Hansen, L.H.; Leigh Gibson, E.; Nielsen, D.S.; Costabile, A. A Prebiotic Intervention Study in Children with Autism Spectrum Disorders (ASDs). Microbiome 2018, 6, 133.
  132. Chen, D.; Yang, X.; Yang, J.; Lai, G.; Yong, T.; Tang, X.; Shuai, O.; Zhou, G.; Xie, Y.; Wu, Q. Prebiotic Effect of Fructooligosaccharides from Morinda Officinalis on Alzheimer’s Disease in Rodent Models by Targeting the Microbiota-Gut-Brain Axis. Front. Aging Neurosci. 2017, 9, 403.
  133. Xin, Y.; Diling, C.; Jian, Y.; Ting, L.; Guoyan, H.; Hualun, L.; Xiaocui, T.; Guoxiao, L.; Ou, S.; Chaoqun, Z.; et al. Effects of Oligosaccharides From Morinda Officinalis on Gut Microbiota and Metabolome of APP/PS1 Transgenic Mice. Front. Neurol. 2018, 9, 412.
  134. Tsao, S.-P.; Nurrahma, B.A.; Kumar, R.; Wu, C.-H.; Yeh, T.-H.; Chiu, C.-C.; Lee, Y.-P.; Liao, Y.-C.; Huang, C.-H.; Yeh, Y.-T.; et al. Probiotic Enhancement of Antioxidant Capacity and Alterations of Gut Microbiota Composition in 6-Hydroxydopamin-Induced Parkinson’s Disease Rats. Antioxidants 2021, 10, 1823.
  135. Perez-Pardo, P.; de Jong, E.M.; Broersen, L.M.; van Wijk, N.; Attali, A.; Garssen, J.; Kraneveld, A.D. Promising Effects of Neurorestorative Diets on Motor, Cognitive, and Gastrointestinal Dysfunction after Symptom Development in a Mouse Model of Parkinson’s Disease. Front. Aging Neurosci. 2017, 9, 57.
  136. 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.
  137. Astarloa, R.; Mena, M.A.; Sánchez, V.; de la Vega, L.; de Yébenes, J.G. Clinical and Pharmacokinetic Effects of a Diet Rich in Insoluble Fiber on Parkinson Disease. Clin. Neuropharmacol. 1992, 15, 375–380.
  138. Ashraf, W.; Pfeiffer, R.F.; Park, F.; Lof, J.; Quigley, E.M.M. Constipation in Parkinson’s Disease: Objective Assessment and Response to Psyllium. Mov. Disord. 1997, 12, 946–951.
  139. Nurrahma, B.A.; Tsao, S.-P.; Wu, C.-H.; Yeh, T.-H.; Hsieh, P.-S.; Panunggal, B.; Huang, H.-Y. Probiotic Supplementation Facilitates Recovery of 6-OHDA-Induced Motor Deficit via Improving Mitochondrial Function and Energy Metabolism. Front. Aging Neurosci. 2021, 13, 668775.
  140. Savignac, H.M.; Corona, G.; Mills, H.; Chen, L.; Spencer, J.P.E.; Tzortzis, G.; Burnet, P.W.J. Prebiotic Feeding Elevates Central Brain Derived Neurotrophic Factor, N-Methyl-d-Aspartate Receptor Subunits and d-Serine. Neurochem. Int. 2013, 63, 756–764.
  141. Bathina, S.; Das, U.N. Brain-Derived Neurotrophic Factor and Its Clinical Implications. Arch. Med. Sci. 2015, 6, 1164–1178.
  142. St. Laurent, R.; O’Brien, L.M.; Ahmad, S.T. Sodium Butyrate Improves Locomotor Impairment and Early Mortality in a Rotenone-Induced Drosophila Model of Parkinson’s Disease. Neuroscience 2013, 246, 382–390.
  143. 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.
  144. Bianchi, V.E.; Herrera, P.F.; Laura, R. Effect of Nutrition on Neurodegenerative Diseases. A Systematic Review. Nutr. Neurosci. 2021, 24, 810–834.
  145. Solfrizzi, V.; Custodero, C.; Lozupone, M.; Imbimbo, B.P.; Valiani, V.; Agosti, P.; Schilardi, A.; D’Introno, A.; la Montagna, M.; Calvani, M.; et al. Relationships of Dietary Patterns, Foods, and Micro- and Macronutrients with Alzheimer’s Disease and Late-Life Cognitive Disorders: A Systematic Review. J. Alzheimer’s Dis. 2017, 59, 815–849.
  146. Metcalfe-Roach, A.; Yu, A.C.; Golz, E.; Cirstea, M.; Sundvick, K.; Kliger, D.; Foulger, L.H.; Mackenzie, M.; Finlay, B.B.; Appel-Cresswell, S. MIND and Mediterranean Diets Associated with Later Onset of Parkinson’s Disease. Mov. Disord. 2021, 36, 977–984.
  147. Paknahad, Z.; Sheklabadi, E.; Derakhshan, Y.; Bagherniya, M.; Chitsaz, A. The Effect of the Mediterranean Diet on Cognitive Function in Patients with Parkinson’s Disease: A Randomized Clinical Controlled Trial. Complement. Ther. Med. 2020, 50, 102366.
  148. Rusch, C.; Beke, M.; Tucciarone, L.; Nieves, C.; Ukhanova, M.; Tagliamonte, M.S.; Mai, V.; Suh, J.H.; Wang, Y.; Chiu, S.; et al. Mediterranean Diet Adherence in People With Parkinson’s Disease Reduces Constipation Symptoms and Changes Fecal Microbiota After a 5-Week Single-Arm Pilot Study. Front. Neurol. 2021, 12, 794640.
  149. Cassani, E.; Barichella, M.; Ferri, V.; Pinelli, G.; Iorio, L.; Bolliri, C.; Caronni, S.; Faierman, S.A.; Mottolese, A.; Pusani, C.; et al. Dietary Habits in Parkinson’s Disease: Adherence to Mediterranean Diet. Park. Relat. Disord. 2017, 42, 40–46.
  150. Maraki, M.I.; Yannakoulia, M.; Stamelou, M.; Stefanis, L.; Xiromerisiou, G.; Kosmidis, M.H.; Dardiotis, E.; Hadjigeorgiou, G.M.; Sakka, P.; Anastasiou, C.A.; et al. Mediterranean Diet Adherence Is Related to Reduced Probability of Prodromal Parkinson’s Disease. Mov. Disord. 2019, 34, 48–57.
  151. Paknahad, Z.; Sheklabadi, E.; Moravejolahkami, A.R.; Chitsaz, A.; Hassanzadeh, A. The Effects of Mediterranean Diet on Severity of Disease and Serum Total Antioxidant Capacity (TAC) in Patients with Parkinson’s Disease: A Single Center, Randomized Controlled Trial. Nutr. Neurosci. 2022, 25, 313–320.
  152. Alcalay, R.N.; Gu, Y.; Mejia-Santana, H.; Cote, L.; Marder, K.S.; Scarmeas, N. The Association between Mediterranean Diet Adherence and Parkinson’s Disease. Mov. Disord. 2012, 27, 771–774.
  153. Strikwerda, A.J.; Dommershuijsen, L.J.; Ikram, M.K.; Voortman, T. Diet Quality and Risk of Parkinson’s Disease: The Rotterdam Study. Nutrients 2021, 13, 3970.
  154. Yin, W.; Löf, M.; Pedersen, N.L.; Sandin, S.; Fang, F. Mediterranean Dietary Pattern at Middle Age and Risk of Parkinson’s Disease: A Swedish Cohort Study. Mov. Disord. 2021, 36, 255–260.
  155. Agarwal, P.; Wang, Y.; Buchman, A.S.; Holland, T.M.; Bennett, D.A.; Morris, M.C. MIND Diet Associated with Reduced Incidence and Delayed Progression of Parkinsonism in Old Age. J. Nutr. Health Aging 2018, 22, 1211–1215.
  156. Lawrie, S.; Coe, S.; Mansoubi, M.; Welch, J.; Razzaque, J.; Hu, M.T.; Dawes, H. Dietary Patterns and Nonmotor Symptoms in Parkinson’s Disease: A Cross-Sectional Analysis. J. Am. Nutr. Assoc. 2022, 1–10.
  157. Koyuncu, H.; Fidan, V.; Toktas, H.; Binay, O.; Celik, H. Effect of Ketogenic Diet versus Regular Diet on Voice Quality of Patients with Parkinson’s Disease. Acta Neurol. Belg. 2021, 121, 1729–1732.
  158. VanItallie, T.B.; Nonas, C.; di Rocco, A.; Boyar, K.; Hyams, K.; Heymsfield, S.B. Treatment of Parkinson Disease with Diet-Induced Hyperketonemia: A Feasibility Study. Neurology 2005, 64, 728–730.
  159. Phillips, M.C.L.; Murtagh, D.K.J.; Gilbertson, L.J.; Asztely, F.J.S.; Lynch, C.D.P. Low-Fat versus Ketogenic Diet in Parkinson’s Disease: A Pilot Randomized Controlled Trial. Mov. Disord. 2018, 33, 1306–1314.
  160. Tidman, M. Effects of a Ketogenic Diet on Symptoms, Biomarkers, Depression, and Anxiety in Parkinson’s Disease: A Case Study. Cureus 2022, 14, e23684.
  161. Mischley, L.K.; Lau, R.C.; Bennett, R.D. Role of Diet and Nutritional Supplements in Parkinson’s Disease Progression. Oxid Med. Cell Longev. 2017, 2017, 6405278.
  162. Kalampokini, S.; Becker, A.; Fassbender, K.; Lyros, E.; Unger, M.M. Nonpharmacological Modulation of Chronic Inflammation in Parkinson’s Disease: Role of Diet Interventions. Park. Dis. 2019, 2019, 7535472.
  163. Jackson, A.; Forsyth, C.B.; Shaikh, M.; Voigt, R.M.; Engen, P.A.; Ramirez, V.; Keshavarzian, A. Diet in Parkinson’s Disease: Critical Role for the Microbiome. Front. Neurol. 2019, 10, 1245.
  164. Gupta, A.; Khanna, S. Fecal Microbiota Transplantation. JAMA 2017, 318, 102.
  165. Tan, P.; Li, X.; Shen, J.; Feng, Q. Fecal Microbiota Transplantation for the Treatment of Inflammatory Bowel Disease: An Update. Front. Pharmacol. 2020, 11, 574533.
  166. Ramai, D. Fecal Microbiota Transplantation: Donor Relation, Fresh or Frozen, Delivery Methods, Cost-Effectiveness. Ann. Gastroenterol. 2018, 32, 30–38.
  167. Varesi, A.; Pierella, E.; Romeo, M.; Piccini, G.B.; Alfano, C.; Bjørklund, G.; Oppong, A.; Ricevuti, G.; Esposito, C.; Chirumbolo, S.; et al. The Potential Role of Gut Microbiota in Alzheimer’s Disease: From Diagnosis to Treatment. Nutrients 2022, 14, 668.
  168. Vendrik, K.E.W.; Ooijevaar, R.E.; de Jong, P.R.C.; Laman, J.D.; van Oosten, B.W.; van Hilten, J.J.; Ducarmon, Q.R.; Keller, J.J.; Kuijper, E.J.; Contarino, M.F. Fecal Microbiota Transplantation in Neurological Disorders. Front. Cell. Infect Microbiol. 2020, 10, 98.
  169. Kang, D.-W.; Adams, J.B.; Gregory, A.C.; Borody, T.; Chittick, L.; Fasano, A.; Khoruts, A.; Geis, E.; Maldonado, J.; McDonough-Means, S.; et al. Microbiota Transfer Therapy Alters Gut Ecosystem and Improves Gastrointestinal and Autism Symptoms: An Open-Label Study. Microbiome 2017, 5, 10.
  170. Evrensel, A.; Ceylan, M.E. Fecal Microbiota Transplantation and Its Usage in Neuropsychiatric Disorders. Clin. Psychopharmacol. Neurosci. 2016, 14, 231–237.
  171. Xu, M.-Q. Fecal Microbiota Transplantation Broadening Its Application beyond Intestinal Disorders. World J. Gastroenterol. 2015, 21, 102.
  172. 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.
  173. Sun, M.-F.; Zhu, Y.-L.; Zhou, Z.-L.; Jia, X.-B.; Xu, Y.-D.; Yang, Q.; Cui, C.; Shen, Y.-Q. Neuroprotective Effects of Fecal Microbiota Transplantation on MPTP-Induced Parkinson’s Disease Mice: Gut Microbiota, Glial Reaction and TLR4/TNF-α Signaling Pathway. Brain Behav. Immun. 2018, 70, 48–60.
  174. Zhao, Z.; Ning, J.; Bao, X.; Shang, M.; Ma, J.; Li, G.; Zhang, D. Fecal Microbiota Transplantation Protects Rotenone-Induced Parkinson’s Disease Mice via Suppressing Inflammation Mediated by the Lipopolysaccharide-TLR4 Signaling Pathway through the Microbiota-Gut-Brain Axis. Microbiome 2021, 9, 226.
  175. Zhong, Z.; Chen, W.; Gao, H.; Che, N.; Xu, M.; Yang, L.; Zhang, Y.; Ye, M. Fecal Microbiota Transplantation Exerts a Protective Role in MPTP-Induced Parkinson’s Disease via the TLR4/PI3K/AKT/NF-ΚB Pathway Stimulated by α-Synuclein. Neurochem. Res. 2021, 46, 3050–3058.
  176. Zhang, T.; Wang, T.; Chen, X.; Zhao, Z.; Chen, Z. Gut Microbiota Relieves Inflammation in the Substantia Nigra of Chronic Parkinson’s Disease by Protecting the Function of Dopamine Neurons. Exp. Ther. Med. 2021, 23, 52.
  177. Zhou, Z.-L.; Jia, X.-B.; Sun, M.-F.; Zhu, Y.-L.; Qiao, C.-M.; Zhang, B.-P.; Zhao, L.-P.; Yang, Q.; Cui, C.; Chen, X.; et al. Neuroprotection of Fasting Mimicking Diet on MPTP-Induced Parkinson’s Disease Mice via Gut Microbiota and Metabolites. Neurotherapeutics 2019, 16, 741–760.
  178. Huang, H.; Xu, H.; Luo, Q.; He, J.; Li, M.; Chen, H.; Tang, W.; Nie, Y.; Zhou, Y. Fecal Microbiota Transplantation to Treat Parkinson’s Disease with Constipation. Medicine 2019, 98, e16163.
  179. Kuai, X.; Yao, X.; Xu, L.; Zhou, Y.; Zhang, L.; Liu, Y.; Pei, S.; Zhou, C. Evaluation of Fecal Microbiota Transplantation in Parkinson’s Disease Patients with Constipation. Microb. Cell. Fact 2021, 20, 98.
  180. Xue, L.-J.; Yang, X.-Z.; Tong, Q.; Shen, P.; Ma, S.-J.; Wu, S.-N.; Zheng, J.-L.; Wang, H.-G. Fecal Microbiota Transplantation Therapy for Parkinson’s Disease. Medicine 2020, 99, e22035.
  181. Segal, A.; Zlotnik, Y.; Moyal-Atias, K.; Abuhasira, R.; Ifergane, G. Fecal Microbiota Transplant as a Potential Treatment for Parkinson’s Disease—A Case Series. Clin. Neurol. Neurosurg. 2021, 207, 106791.
  182. Knott, C.; Stern, G.; Wilkin, G.P. Inflammatory Regulators in Parkinson’s Disease: INOS, Lipocortin-1, and Cyclooxygenases-1 and -2. Mol. Cell. Neurosci. 2000, 16, 724–739.
  183. Li, J.; Ma, S.; Chen, J.; Hu, K.; Li, Y.; Zhang, Z.; Su, Z.; Woodgett, J.R.; Li, M.; Huang, Q. GSK-3β Contributes to Parkinsonian Dopaminergic Neuron Death: Evidence From Conditional Knockout Mice and Tideglusib. Front. Mol. Neurosci. 2020, 13, 81.
  184. Chen, X.; Hu, Y.; Cao, Z.; Liu, Q.; Cheng, Y. Cerebrospinal Fluid Inflammatory Cytokine Aberrations in Alzheimer’s Disease, Parkinson’s Disease and Amyotrophic Lateral Sclerosis: A Systematic Review and Meta-Analysis. Front. Immunol. 2018, 9, 2122.
  185. Choi, H.H.; Cho, Y.-S. Fecal Microbiota Transplantation: Current Applications, Effectiveness, and Future Perspectives. Clin. Endosc. 2016, 49, 257–265.
  186. Schmulson, M.; Bashashati, M. Fecal Microbiota Transfer for Bowel Disorders: Efficacy or Hype? Curr. Opin. Pharmacol. 2018, 43, 72–80.
  187. Shanahan, F.; Quigley, E.M.M. Manipulation of the Microbiota for Treatment of IBS and IBD—Challenges and Controversies. Gastroenterology 2014, 146, 1554–1563.
  188. Lopetuso, L.R.; Ianiro, G.; Allegretti, J.R.; Bibbò, S.; Gasbarrini, A.; Scaldaferri, F.; Cammarota, G. Fecal Transplantation for Ulcerative Colitis: Current Evidence and Future Applications. Expert Opin. Biol. Ther. 2020, 20, 343–351.
  189. Wang, J.-W.; Kuo, C.-H.; Kuo, F.-C.; Wang, Y.-K.; Hsu, W.-H.; Yu, F.-J.; Hu, H.-M.; Hsu, P.-I.; Wang, J.-Y.; Wu, D.-C. Fecal Microbiota Transplantation: Review and Update. J. Formos. Med. Assoc. 2019, 118, S23–S31.
  190. Aroniadis, O.C.; Brandt, L.J. Fecal Microbiota Transplantation. Curr. Opin. Gastroenterol. 2013, 29, 79–84.
More
Information
Subjects: Biology
Contributors MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register : , , , , , , , ,
View Times: 429
Revisions: 2 times (View History)
Update Date: 31 Oct 2022
1000/1000