MS, Parkinson, Alzheimer
Impression of publications on the relevance of the microbiome
Neurological disorders often have an inflammatory aspect, and here too relationships with an altered microbiome are not uncommon. This may seem a bit unlikely, but the intestines are very rich with nerves and have two-way traffic with the brain. The evidence that the microbiome can direct modulation of the central nervous system, and vice versa, is accumulating. Indications for the relationship with the microbiome have been found in:
Multiple sclerosis (MS)
In MS patients, abnormalities in the blood concentrations of substances of bacterial origin, which are known to affect neuroinflammation, have been found (1). Differences in the composition of the microbiome have also been found in MS patients, the most striking difference being a lower number of bacteria from species that can dampen autoimmune reactions (2-4). With modern techniques, traces of bacteria are now also found in organs that were considered sterile. An intriguing study compared bacteria in the brains of deceased MS patients with those in the brains of other deceased persons and found remarkable differences there too, with a strong correlation between the bacterial counts found and the disease-related immune response (5). The first studies of the influence of probiotics in MS patients show shifts in the microbiome towards that of healthy subjects, cautious indications of a decrease in autoimmune activity, and a reduction in disability and mental problems (6-8).
This is the second most common neurodegenerative disease, in which especially the motor regions in the brain are damaged. An important characteristic of Parkinson’s is the reduced production of dopamine. The microbiome regulates the production of enzymes for dopamine production, and bacteria also make dopamine themselves and are responsible for half of all dopamine in the body (9). Many patients appear to suffer from constipation before movement problems occur (9-11). Constipation occurs in about 80% of patients and is associated with accumulation of A-synuclein, damage to intestinal nerves, and increased permeability of the intestinal wall (9,11). In Parkinson’s, abnormalities in the composition of the microbiome have also been found, in which the amount of a specific bacterial family correlated with the severity of the movement problems (10). Finally, small intestine bacterial overgrowth (small intestine bacterial overgrowth) has also been associated with Parkinson’s (9). Although there are strong indications for a role of the microbiome in Parkinson’s, no studies have yet been published on a direct modulation of the microbiome (via probiotics or poo transplantation, for example).
An important hypothesis about the cause of Alzheimer’s is that this disease is the result of amyloid plaque accumulation. In an animal model, altered microbiome composition has been shown to contribute to amyloid plaque deposition (10). Moreover, a different composition of the microbiome compared to healthy persons has also been found in Alzheimer’s patients (12). In the bacterial genera where the abnormalities were greatest, the amount was correlated with the severity of the disease (12). Remarkable is the finding that more and different bacteria are found in the brains of deceased Alzheimer’s patients than in the brains of healthy people (10). In addition, in the brains of Alzheimer’s patients, elevated levels of endotoxins of bacterial origin (LPS) have been found, ranging from 3-fold to, in some patients with advanced Alzheimer’s, sometimes as much as 26 times as many as in healthy controls (13). These substances cause neuroinflammatory responses, similar to the neuroinflammation found in Alzheimer’s (14). Finally, a small study of the effect of probiotics in Alzheimer’s patients suggests an improvement in cognitive functioning and a reduction of inflammatory factors (7)
1. Clemente JC, Manasson J, Scher JU. The role of the gut microbiome in systemic inflammatory disease. BMJ. 2018; 360: j5145.
2. Miyake S, Kim S, Suda W, Oshima K, Nakamura M, Matsuoka T, Chihara N, Tomita A, Sato W, Kim SW, et al. Dysbiosis in the Gut Microbiota of Patients with Multiple Sclerosis, with a Striking Depletion of Species Belonging to Clostridia XIVa and IV Clusters. PLoS ONE [Internet]. 2015 [cited 2018 May 26]; 10. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4569432/
3. Chen J, Chia N, Kalari KR, Yao JZ, Novotna M, Soldan MMP, Luckey DH, Marietta EV, Jeraldo PR, Chen X, et al. Multiple sclerosis patients have a distinct gut microbiota compared to healthy controls. Sci Rep [Internet]. 2016 [cited 2018 May 26]; 6. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4921909/
4. Cekanavi ciute E, Yoo BB, Runia TF, Debelius JW, Singh S, Nelson CA, Kanner R, Bencosme Y, Lee YK, Hauser SL, et al. Gut bacteria from multiple sclerosis patients modulate human T cells and exacerbate symptoms in mouse models. Proc Natl Acad Sci U S A. 2017; 114: 10713–8.
5. Branton WG, Lu JQ, Surette MG, Holt RA, Lind J, Laman JD, Power C. Brain microbiota disruption within inflammatory demyelinating lesions in multiple sclerosis. Sci Rep [Internet]. 2016 [cited 2018 May 26]; 6. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5125007/
6. Tankou SK, Regev K, Healy BC, Tjon E, Laghi L, Cox LM, Kivisäkk P, Pierre IV, Lokhande H, Gandhi R, et al. A probiotic modulates the microbiome and immunity in multiple sclerosis. Ann Neurol. 2018;
7. Kouchaki E, Tamtaji OR, Salami M, Bahmani F, Daneshvar Kakhaki R, Akbari E, Tajabadi-Ebrahimi M, Jafari P, Asemi Z. Clinical and metabolic response to probiotic supplementation in patients with multiple sclerosis: A randomized, double- blind, placebo-controlled trial. Clin Nutr Edinb Scotl. 2017; 36: 1245–9.
8. Tankou SK, Regev K, Healy BC, Cox LM, Tjon E, Kivisakk P, Vanande IP, Cook S, Gandhi R, Glanz B, et al. Investigation of probiotics in multiple sclerosis. Mult Scler Houndmills Basingstoke Engl. 2018; 24: 58–63.
9. Parashar A, Udayabanu M. Gut microbiota: Implications in Parkinson’s disease. Parkinsonism Relat Disord. 2017; 38: 1–7.
10. Kim N, Yun M, Oh YJ, Choi H-J. Mind-altering with the gut: Modulation of the gut-brain axis with probiotics. J Microbiol Seoul Korea. 2018; 56: 172–82.
11. Felice VD, Quigley EM, Sullivan AM, O’Keeffe GW, O’Mahony SM. Microbiota-gut-brain signaling in Parkinson’s disease: Implications for non-motor symptoms. Parkinsonism Relat Disord. 2016; 27: 1–8.
12. Vogt NM, Kerby RL, Dill-McFarland KA, Harding SJ, Merluzzi AP, Johnson SC, Carlsson CM, Asthana S, Zetterberg H, Blennow K, et al. Gut microbiome alterations in Alzheimer’s disease. Sci Rep [Internet]. 2017 [cited 2018 May 27]; 7. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5648830/
13. Zhao Y, Jaber V, Lukiw WJ. Secretory Products of the Human GI Tract Microbiome and Their Potential Impact on Alzheimer’s Disease (AD): Detection of Lipopolysaccharide (LPS) in AD Hippocampus. Front Cell Infect Microbiol [Internet]. 2017 [cited 2018 May 27]; 7. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5504724/
14. Lin L, Zheng LJ, Zhang LJ. Neuroinflammation, Gut Microbiome, and Alzheimer’s Disease. Mol Neurobiol. 2018;