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Microbes

 * human gut is mainly inhabited by two phyla of bacteria – Firmicutes and Bacteroidetes (Bacteroides and Prevotella).
 * Prevotella - plants and fiber; a/w inflammation; break down complex carbohydrates, providing short chain fatty acids (SCFA’s) (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4747781/) can degrade a broad spectrum of plant polysaccharides and mucin glycoproteins in the mucosal layer of the gut; also can be inflammatory
 * Bacteroides - fats and animal proteins; however main sources of energy for Bacteroides species in the gut are complex host-derived and plant glycans.
 * probiotic Bacillus sp. JPJ which can catalyze an efficient conversion of L-tyrosine to L-DOPA
 * certain bacteria (genus Lactobacillus and species Enterococcus faecalis) metabolize l-dopa to dopamine through the action of tyrosine decarboxylase, potentially individualizing treatment for PD
 * Decreased abundance of Prevotellaceae and increased abundance of Lactobacillaceae have been associated with decreased levels of the gut hormone ghrelin.75 Gut hormones such as ghrelin regulate nigrostriatal dopamine function and may restrict neurodegeneration in PD
 * Most consistent: increased akkermansia (Verrucomicrobiaceae); decreased Prevotella (Prevotellaceae); increased Bifidobacteria (Bifidobacteriaceae); decreased Lachnospiraceae. Increased Lactobacillaceae, possibly 2/2 COMT inhib.
 * Fasting as gastroprotective 2/2 ghrelin.

Cross sectionals from "The gut microbiome in neurological disorders" - Lancet Neurol
Notes:
 * caution is needed when examining the available data because they are largely derived from small cohorts and do not provide a longitudinal perspective
 * vagotomy protective
 * When mice were colonised with the microbiota of patients with Parkinson’s disease via faecal microbiota transplantation, they developed motor deficits and neuroinflammation, two hallmark symptoms of Parkinson’s disease.
 * MAO inhibitors and amantadine increase microbiota richness
 * OTU = operational taxonomic unit

Increased in PD

 * Anaerotruncus (Clostridiaceae)
 * Akkermansia muciniphila x 4 - obesity; mucin degradation
 * Verrucomicrobiaceae (genus Akkermansia)
 * Bacteroidetes x 4 <-- contradiction
 * B fragilis
 * Bifidobacterium <--contradiction
 * Clostridium coccoides + leptum x 3
 * Enterobacteriaceae
 * Firmicutes
 * Oxalobacteraceae
 * Proteobacteria
 * Ruminococcaceae increased with length of PD - associated with long term fruit/vegetable intake
 * Verrucomicrobia

Decreased in PD

 * Bacteroidetes <-- contradiction
 * Bifidobacterium <-- contradiction
 * Erysipelotrichaceae
 * Enterococcaceae
 * Firmicutes
 * Faecalibacterium
 * Lachnospiraceae (blautia) x 2 (Sasmita study says increased)
 * Lactobacillaceae
 * Prevotellaceae x 2

Lubomski (2019). Parkinson’s disease and the gastrointestinal microbiome. Journal of Neurology

 * Need to increase prevotella without SCFA production.
 * Family ends with -aceae
 * Smokers - higher Bacteroides and Prevotella
 * Smokers who quit - decreased abundance Protebacteria; increased Firmicutes and Actinobacteria
 * Coffee - higher Bacteroides, Prevotella; Bifido; lower Clostridium, E. coli
 * Red wine - F prausnitzii
 * Plant carbohydrates/fiber - Prevotella/paraprevotella
 * Antimal fat/protein - Bacteroides
 * Sugar/saturated fat - lower Bifidobacterium, higher Firmicutes/Proteobacteria
 * Sour nonfat milk - Leuconostoc mesenteroides/lactis
 * Whole milk - lower diversity
 * Prevotella dominant - higher urate
 * Aging - reduced lactobacili, bacteroides/prevotella, faecalibacterium; increased ruminococcus, atopobim, enterobacteriaceae
 * Exercise - Roseburia, clostridiales, lachnospiraceae, erysipelotrichacae
 * minocycline - neuroprotective; rebalance dysbiosis by reducing firmicutes:bacteroidetes ratio; ampicillin, metronidazole, cefrtiaxone, plymyin B may be neuroprotective
 * Progressed PD patients have Firmicutes-dominated enterotype; Prevotella less abundant in patients with faster disease progression.
 * Compared to lean participants, those who were overweight/obese had higher SCFAs overall: higher fecal acetate, propionate, butyrate, and valerate.
 * Higher Bacteroides/Prevotella counts were associated with lower fecal SCFAs. Firmicutes:Bacteroides ratio correlated with higher fecal SCFAs.

Up

 * Akkermansia++++ (Verrucomicrobia) - genus - a/w obesity and mucin degradation; high fat diet; antibiotics, polyphenols (cranberry, green tea, grape), linoleic acid, oats, anti-FODMAP (sugar, milk, fruit, beans), whole grain, metformin, fish oil; artificial sweeteners reduce
 * anaerotruncus++ -genus
 * acidaminococcus - genus
 * acinetobacter - genus
 * barnseillaceae - genus
 * Bifidobacterium++ - genus - kefir, yogurt, pickles, kimchi, cured meat
 * bradyrhizzaceae - genus
 * christensenella - genus
 * catabacter up - genus
 * clostridiaceae - genus
 * clostridium+++ - genus - anaerobic; hypomobility
 * clostridialis (family)
 * Coriobacteraecae (family)
 * enterobacteriacea (family) ++ postural instability correlates with relative abundance; spoiled food - https://pubmed.ncbi.nlm.nih.gov/25476529/ COMT inhibitors decrease - Scheperjans, F., Aho, V., Pereira, P. A. B., Koskinen, K., Paulin, L., Pekkonen, E., … Auvinen, P. (2014). Gut microbiota are related to Parkinson’s disease and clinical phenotype. Movement Disorders, 30(3), 350–358. doi:10.1002/mds.26069
 * enterococcaceae - genus
 * Enterococcaceae (family)
 * enterococcus - genus
 * erysipelothrix (family)
 * escherichia/shigella - genus
 * lactobacillaceae/lactobacillus+++ (Firmicutes)
 * megamonas - genus
 * megasphaera - genus
 * Moraxellaceae (family)
 * oscillospira - genus
 * oxallobacteraceae - family
 * proteus - genus
 * Ralstonia - genus
 * Ruminococcus - genus - starchy plants; PUFAs
 * streptococcus - genus
 * Verrucomicrobiaceae (family) +++
 * veillonellaceae (family)


 * Motor complications - aquabacteirum, peptococcus, sphingomonas
 * UPDRS III - Anaerotruncus, clostridium, lachnspiraceae
 * Changes in UPDRS - lower Bifidobacteirum and Atopobium
 * Postural instability, gait distrubance, cognition - decreased lachnospiraceae; increased lactobacillaceae and chritensenellaceae
 * Depression altered abundance anaerotruncus and higher christensella, clostridium, oscillibacter
 * Cognition issues with Butyriccoccus and Clostridium
 * Delusons/hallucinations - lower bifidobacterium
 * REM sleep disorder - anaerotruncus up; prevotellaceae down
 * COMT + anticholinergic - increased lactobacillaceae and clostridialis
 * COMT alone - Decreased firmicutis, lachnospiraceae, ruminococcaceae; increased actinobacteria, porphyromonadaceae, lactobacillaceae, proteobacteria
 * Levodopa - increased bacillaceae; decreased dorea and phascolarctobacterium

Down

 * Atopobium
 * B fragilis
 * Bacteroidetes: Prevotellaceae, Prevotella down
 * Bifidobacterium ++
 * Blautia - genus
 * Dorea - genus
 * Faecalibacterium down - genus
 * Lachnospiraceae - genus
 * Roseburia - genus - digests plant cell walls (beta mannans); might cause UC
 * Decreased short chain fatty acids; however, mice fed SCFAs develop parkinsons and a-syn aggregation - from fibers and resistant starch

Healthy controls

 * actinomycetaceae
 * bacteroides
 * bacteroides fragilis
 * blautia++
 * brevibacteriaceae
 * brucellaceae
 * Caprobacillaceae
 * caprococcus
 * clostridium
 * comamonoadaceae
 * dorea++
 * enterococcaceae
 * faecalibacterium+++++
 * gamellaceae
 * halomonadaceae
 * hyphomonodaceae
 * idomarinaceae
 * intrasporangiaceae
 * lactobacillaceae
 * Lachnospiraceae+++++
 * methanobacteriaceae
 * methylobacteraceae
 * micrococcaceae
 * Pasteurellaceae++
 * Prevotellaceae++
 * prevotella++
 * roseburia+++
 * ruminococcus
 * sphongomondaaceae
 * Strepcoccaceae
 * xanthomonadaceae

Alpha synuclein and microbiome

 * Alpha-Synuclein Pathology and the Role of the Microbiota in Parkinson's Disease.
 * Caudo-rostral brain spreading of α-synuclein through vagal connections.
 * Increased activation of toll like receptors (TLR2 and TLR4) in Parkinson's Disease. Upregulation of these receptors appears to inhibit autophagy and clearance of alpha synuclein.

Bacterial changes

 * Colonic bacterial composition in Parkinson's disease - Keshavarzian 2015 (8.7) - Blautia, Coprococcus, and Roseburia - butyrate-producing; decreased in PD patients. Faecalibacterium decreased in PD. Proteobacteria (genus Ralstonia) pro-inflammatory; more in PD than controls. PD higher lipopolysaccharides and type three secretion systems, which can be inhibited by butyrate.
 * Gut microbiota are related to Parkinson's disease and clinical phenotype. Scheperjans 2015 (8.7) - Prevotellaceae reduced with PD; increase in Enterobacteriaceae is correlated with severity of postural instability/gait difficulty.
 * Gut microbiota in Parkinson disease in a northern German cohort. Lactobacillus more abundant in PD. - Hopfner 2017 (3.1)Barnesiella and Enterococcus more in PD patients in north German cohorts.
 * Short chain fatty acids and gut microbiota differ between patients with Parkinson's disease and age-matched controls - Unger 2016 - Bacteroidetes and Prevotellaceae reduced in PD; Enterobacteriaceae increased in PD. - Unger 2016 (3.9)
 * The prodromal microbiome - Scheperjans 2018 - Increases in Lactobacillus, Akkermansia, and Bifidobacterium increased in PD; Prevotella, Blautia, and Faecalibacterium decreased in PD. - Scheperjans 2018 (8.7)
 * Increased abundance of Akkermansia and Lactobacillus Bifidobacterium in PD and decreased abundance of Prevotella, Faecalibacterium and Blautia.

Ketogenic

 * Ketogenic diet increased the relative abundance of putatively beneficial gut microbiota (Akkermansia muciniphila and Lactobacillus), and reduced that of putatively pro-inflammatory taxa (Desulfovibrio and Turicibacter).

We confirmed a decrease of Prevotella copri in PD and in addition found decreased Eubacterium biforme and Clostridium saccharolyticum and increased Akkermansia muciniphila as well as Alistipes shahii.

The deteriorated group had lower counts of Bifidobacterium, B. fragilis, and Clostridium leptium than the stable group at year 0 but not at year 2, suggesting that the deteriorated group may demonstrate accelerated lowering of these bacteria at year 0.

Our results (Table S3 E) confirmed many of the reported associations including elevated levels of Akkermansia, Lactobacillus, and Bifidobacterium and reduced levels of Lachnospiraceae in PD. We did not, however, replicate the reported association with Prevotellaceae (case vs. control P=0.57, association with UPDRS III score P=0.24). Several studies have implicated depletion of short chain fatty acids (SCFA) in the pathogenesis PD. CFA is made by bacteria in the gut, notably Lachnospiraceae. Our study shows reduced levels of Lachnospiraceae in PD, which is consistent with SCFA depletion.

Bacteroides was the most abundant genus in both groups, and no statistically significant difference was detected in the presence of Bifidobacterium, Eggerthella, and Adlercreutzia species. However, we detected a depletion of Prevotellaceae and Lachnospiraceae species in PD patients, which is consistent with previous studies. Furthermore, our analysis of less abundant families revealed reduced representation of Lactobacillaceae and Streptococcaceae in the PD group.