Fecal transplant against Parkinson’s disease
Parkinson’s disease is the second most common neurodegenerative disease. All that can currently be done is alleviate its symptoms. Faced with the failure of current treatments, a Chinese team conducted a non-clinical study to explore the involvement of the microbiota and the promising effects of fecal transplant.
Parkinson’s disease is characterized by the progressive loss of dopaminergic neurons in the nigrostriatal pathway. The neurodegenerative process spreads, explaining the occurrence of motor signs (including axial signs) and non-motor signs (cognitive problems, for example) resistant to dopaminergic treatment. The emerging role of the intestinal microbiota and its metabolites in the pathogenesis of the disease is still poorly identified. To study it, researchers worked on an animal model of Parkinson’s disease* and fecal transplant of healthy microbiota (FMT) to correct the symptoms of the disease and understand the mechanisms involved.
First observation: a difference in microbial composition was detected between healthy mice and Parkinsonian mice. The latter display a decrease in the bacterial groups Firmicutes and Clostridiales, and an increase in the groups Proteobacteria, Turicibacterales and Enterobacteria. This composition is a reflection of the dysbiosis observed in Parkinson’s patients, in whom increased levels of Enterobacteria and Proteobacteria, known to cause intestinal inflammation, have been observed. Finally, the authors show that the transfer of healthy microbiota to Parkinsonian mice corrects the dysbiosis observed.
Regulating the sources of brain inflammation
Short-chain fatty acids (SCFA), which can cross the blood-brain barrier and are involved in microglial neuroinflammation, are one of the components regulating the gut-brain axis and might be another potential mediator. Parkinsonian mice have increased levels of SCFA and FMT allowed for restoration of a normal level of these metabolites which are harmful to the brain. The study also highlighted several signaling pathways involved in both intestinal inflammation and neuroinflammation: the TLR4/TBK1/NF-jB/TNF-α pathways. It thus seems that fecal transplant of healthy microbiota can not only improve the dysbiosis but also diminish brain and intestinal inflammation by modulating these signaling pathways.
Fecal transplant improves motor function
Fecal transplant of healthy microbiota also led to a reduction in bradykinesia, an improvement in muscle strength and balance. The fall in dopamine and serotonin levels observed in Parkinsonian mice was very significantly corrected by the FMT (an increase of 50 to 75%). FMT might also inhibit the reduction in dopaminergic neurons. Fecal transplant seems to be capable of correcting numerous anomalies caused by dysbiosis and reducing neuroinflammation. Already explored in the treatment of multiple sclerosis and autism, FMT may prove promising in the years to come. Additional studies could also reveal new molecular markers capable of increasing the specificity and sensitivity of the diagnosis of Parkinson’s disease.
*Animal model of Parkinson’s disease: mice treated with MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine), a neurotoxin which causes degeneration of dopamine neurons, simulating the disease in man.
M.-F. Sun et al. 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., févr. 2018.