Another step forward in sorting out the Parkinson’s disease (PD)/microbiome connection. Researchers at the Quadram Institute in the UK conducted a meta-analysis of the gut microbiome in those with Parkinson’s disease.[i] Prior to this work, there had not as yet been a consensus as to what alterations are definitively associated with PD. Various studies have used different methodologies and to boot, there are inherent differences in the microbiomes of people around the world, shaped by lifestyles and diets. For example, Lactobacillaceae has been found to be at high levels in those from the West, but this is never found in Chinese PD patients. Another inconsistency: many studies have found a depletion of species of Prevotellaceae, but many have not.
To overcome these inconsistencies these researchers reanalyzed the data from 10 different studies, and compared them to controls: 1200 samples collected from people in 6 different countries around the world. This vast amount of data allowed them to see a clear pattern emerge: “In agreement with previous studies, we show that the gut microbiome of PD patients significantly differs from those of controls.” Firstly, they confirmed that those with PD have low levels of butyrate-producing bacteria. Remember that the short-chain fatty acid (SCFA), butyrate, is crucial in the health of the lining of the gut. (You can read more about that here.) Low levels of butyrate are associated with inflammation of the gut lining and increased permeability (i.e. leaky gut). (Similar findings are found in patients with inflammatory bowel disease, and here is a fact that I did not know: IBD patients have a 20-30% increased risk of developing PD.) From the paper: “Butyrate and other SCFA are not only relevant for gut health, but they can also influence the enteric nervous system (ENS), have systemic anti-inflammatory properties, promote normal microglia development, and potentially affect epigenesis in the CNS.”
Secondly, bacteria which produce methane are at abnormally high levels in those with PD. Thirdly, PD patients have an increased level of bacteria that degrade mucus. The combination of these two findings might well explain the constipation issues that plague nearly everyone with the disease. (In fact, as I’ve mentioned before, chronic constipation is one of the earliest signs of impending PD.) To sum up, “Enrichment of the genera Lactobacillus, Akkermansia, and Bifidobacterium and depletion of bacteria belonging to the Lachnospiraceae family and the Faecalibacterium genus, both important short-chain fatty acids producers, emerged as the most consistent PD gut microbiome alterations.” Low levels of Lachnospiraceae and Faecalibacterium have been detected in other neuro-inflammatory and neurodegenerative disorders (including multiple sclerosis). And Akkermansia, which is so often found to have probiotic properties, is another of those two-faced bacterial species we’ve seen in other species, like B.fragilis: “Akkermansia has been repeatedly shown to be more abundant in PD compared to control. Akkermansia spp is considered beneficial for human health and is potential probiotics, as they fortify the integrity of the epithelial cell layer and can modulate the immune system. However, contrasting results regarding the influence of Akkermansia spp on gut health exist.Recently, safety concerns have been raised about the use of A.municiphila as a probiotic, as its enrichment in neurodegenerative diseases (e.g., Alzheimer’s disease, multiple sclerosis) could contribute to the progression of neural pathologies by degrading mucin, increasing gut inflammation and permeability and finally leading to higher endotoxaemia, and systemic inflammation.” (You can read more about that here.)
What is still unknown is cause and effect: that is, do these microbiome changes precede the development of PD or are they the result of the disease? More than that, can using probiotics, prebiotics, fecal transplant, etc. modulate the gut biome and attenuate the disease? Or stop it from developing in the first place? Dr. Stefano Romano, the lead researcher, states, “The restoration of a balanced microbiome in patients might alleviate some of the symptoms of Parkinson’s, and this is a really exciting route of research we are exploring.”[ii]
[ii] Stefano Romano et al. Meta-analysis of the Parkinson’s disease gut microbiome suggests alterations linked to intestinal inflammation, npj Parkinson’s Disease (2021). DOI: 10.1038/s41531-021-00156-z