Ex-Vivo Discussion & Conclusions

Objective

The research objective of the study was to characterize the impact of a series of test products, including some prebiotic and food bar blends, on the gut microbiota of Parkinsons’ Disease (PD) patients. 

Methods

The impact on metabolite production (key fermentation parameters (pH, gas, SCFA, bCFA)) was assessed at 24h after introduction of the test products in the colonic environment of PD patients, as simulated with the ex vivo SIFR® technology. Six different test subjects were included, which is important since it has been established that there are marked interpersonal differences among the human population (1). The test products were compared against a no-substrate control.

The high technical reproducibility of the SIFR® technology was demonstrated by the minor variation observed across technical replicates, i.e., the coefficient of variation (= SD/AVG) was on average 1.94% for analysis of key fermentation parameters. This very high technical reproducibility renders the SIFR® technology very sensitive to decipher changes in the human gut microbiome.

Results

All test products, except market leading stool softener propylene glycol, demonstrated stimulatory effects on microbial metabolic activity to varying degrees. Notably, the NeuroFiber Prebiotic Fiber powder blend and the Dark Chocolate Cherry NeuroFiber bar products significantly boosted the production of short-chain fatty acids (SCFAs) such as acetate, propionate, and butyrate, which are typically found at lower levels in both serum and fecal samples of Parkinson's disease (PD) patients (43,44). 

The combination of NeuroFiber Powder blend with green tea extract exhibited higher specificity towards propionate and acetate/butyrate. Further, the effects on SCFA production were particularly potent in the bar-form of NeuroFIber, where the key ingredients were combined with additional whole food excipients.

Discussion

Health benefits of gut microbiota-derived SCFAs are well-documented. SCFAs regulate epithelial barrier function as well as mucosal and systemic immunity (44-45). Additionally, SCFAs influence the gut-brain axis by directly stimulating the vagal afferents of the vagus nerve and affecting the intestinal endocrine release of hormones (46). SCFAs can also enter the circulation and cross the blood-brain barrier, where they exert beneficial effects, such as maintaining blood-brain barrier integrity and reducing peripheral inflammation. However, the role of SCFAs in neuroinflammation remains controversial, as studies in animal models have shown conflicting results, with SCFAs either inhibiting or promoting neuroinflammation in mice (46–48).

SCFAs may also play a role in managing several Parkinson’s disease (PD) symptoms. Constipation, a prevalent non-motor symptom in PD, occurs more frequently in PD patients than in the general population (49). Research has shown that acetic acid can increase the water content in feces, while butyric acid can decrease transit time and enhance intestinal mobility. These effects may help alleviate constipation symptoms in PD patients, providing potential relief from one of the more common symptoms of the disease (50). 

For more details on either study please email info@sorriditherapeitucs.com and the team will be happy to provide more information.

Braak’s groundbreaking theory, introduced in 2003, proposes that Parkinson’s disease may begin in the gut. According to this hypothesis, harmful pathogens travel via the vagus nerve to the brain, contributing to neurodegeneration.

An Argument For Treating The Gut In Parkinson’s Disease (PD)

  • 2003

    Braak, et al hypothesized that “PD originates outside the CNS, caused by a yet unidentified pathogen” and propagates to the brain via the vagus nerve.

  • 2011

    Forsyth, et al demonstrated increased intestinal permeability (leaky gut) in PD patients vs controls. In addition, leaky gut correlated with increased E coli and α-synuclein presence in the intestinal mucosa.

  • 2012

    Alkaly, et al concluded from a study of 257 PD patients and 198 controls, that higher adherence to a Mediterranean Diet was associated with reduced odds for PD development.

  • 2015-16

    Erny, et al 2015, Malcovitch-Natan, et al 2016 and Rooks, et al 2016 demonstrate that gut bacteria control the differentiation and function of immune cells in the intestine, periphery and brain.

  • 2016

    Unger, et al analyzed fecal short chain fatty acids (SCFA’s) in 34 PD patients vs age matched controls. SCFA’s were significantly reduced in PD patients vs controls. Additionally, age matched controls had lower SCFA’s compared to a younger control group.

  • 2016

    Sampson, et al, in a PD mouse model, showed that colonization of mice with microbiota from PD patients enhances physical impairment compared to transplants from healthy donors.

  • 2018

    Schwiertz, et al confirmed elevated levels of fecal calprotectin and other inflammatory markers in PD vs controls. Calprotectin: 87.1 vs 25.3

  • 2019

    Kimeta, et al, in a mouse model of PD, injected pathological α-synuclein (PAS) into the duodenal and pyloric muscularis layer. PAS spread to the brain, but not in animals with a truncal vagotomy.

  • 2022

    Abdel-Haq, et al demonstrated that a prebiotic diet attenuates motor deficits and reduces α-synuclein aggregation in the substantia nigra in a mouse model of PD.

  • 2023

    Hall, et al published an open label study of 20 PD patients treated with a prebiotic fiber bar for 14 days. Results indicated beneficial changes in the fecal microbiota, SCFA, inflammation, and systemic NfL levels.

43. Wu, G. et al. Serum short-chain fatty acids and its correlation with motor and non-motor symptoms in Parkinson’s disease patients. BMC Neurol 22, 13 (2022).

44. Chen, S.-J. et al. Association of Fecal and Plasma Levels of Short-Chain Fatty Acids With Gut Microbiota and Clinical Severity in Patients With Parkinson Disease. Neurology 98, (2022).

45. Mann, E. R., Lam, Y. K. & Uhlig, H. H. Short-chain fatty acids: linking diet, the microbiome and immunity. Nat Rev Immunol 24, 577–595 (2024).

46. Duan, W.-X., Wang, F., Liu, J.-Y. & Liu, C.-F. Relationship Between Short-chain Fatty Acids and Parkinson’s Disease: A Review from Pathology to Clinic. Neurosci. Bull. 40, 500–516 (2024).

47. Metzdorf, J. & Tönges, L. Short-chain fatty acids in the context of Parkinson’s disease. Neural Regen Res 16, 2015 (2021).

48. Sampson, T. R. et al. Gut Microbiota Regulate Motor Deficits and Neuroinflammation in a Model of Parkinson’s Disease. Cell 167, 1469-1480.e12 (2016).

49. Pedrosa Carrasco, A. J., Timmermann, L. & Pedrosa, D. J. Management of constipation in patients with Parkinson’s disease. npj Parkinson’s Disease 4, 6 (2018).

50. Xiong, R.-G. et al. Health Benefits and Side Effects of Short-Chain Fatty Acids. Foods 11, 2863 (2022).immunity. Nat Rev Immunol 24, 577–595 (2024).