TABLE 4.

Microbial intervention in Parkinson’s disease

Source	Study design	Sample size (n)	Study population	Microbial strains	Study duration	Key finding(s)
Fecal microbiota transplantation
Huang et al., 2019 (451)	Human case report	1 participant	A 71-yr-old male patient presented with 7 yrs of PD and intractable constipation	FMT was obtained a 26-yr-old male	12 wks	Probable therapeutic effects of gut microbiome reconstruction on PD patients, especially those with gastrointestinal symptoms.
Sun et al. 2018 (452)	Preclinical animal study	10 to 15 per group	8-wk-old male C57BL/6 mice: (i) normal control without any treatment (n = 15); (ii) MPTP+PBS group (n = 15); and (iii) MPTP+FMT group (n = 15)	Collection of fresh fecal pellets from PD mice or healthy control mice	1 wk	FMT ameliorates motor symptoms of PD mice.
						Improvement of serotonin content of PD mice and striatal dopamine resulted by FMT.
						Reducing the glial-mediated neuroinflammation through normal SCFAs improvement by FMT.
						Reducing the gut inflammation and neuroinflammation probably by suppressing TLR4/TBK1/NF-jB/TNF-α signaling pathway.
Zhou et al., 2019 (453)	Preclinical animal study	8 per group	6-wk-old male C57BL/6J mice separated into four groups randomly: (i) NS-AL group (normal saline injection + fed ad libitum); (ii) NSFMD group (normal saline injection + fasting diet); (ii) MPTP-AL group (MPTP + fed ad libitum); and (iv) MPTP-FMD group (MPTP + fasting diet)	Feces from fed ad libitum, fasting-mimicking diet, and normal mice treated with saline by intraperitoneal injection	4 wks	Recovering the motor function via FMD.
						Improvement in the degeneration of dopaminergic neurons in the substantia nigra.
						Increasing the levels of 5-HT and DA in the striatum of PD mice, possibly by reshaping gut microflora to modulate microbial dysbiosis, that contributes to the alterations in SCFAs.
Probiotics
Borazabadi et al., 2018  (454)	Randomized, double-blind, placebo-controlled trial	50 participants	50 individuals were randomly divided into two groups to take either placebo (n = 25 each group, one capsule daily) or 8 × 109 CFU/day probiotic supplements	Probiotic capsule comprised of Lactobacillus acidophilus L. fermentum, L. reuteri, and Bifidobacterium bifidum	12 wks	Enhancement of TNF-α, TGF-β, IL-1, IL-8, and PPAR-γ gene expression in subjects with PD via probiotic supplementation.
						No impact on VEGF and LDLR gene expression, oxidative stress, and inflammation biological markers.
Tamtaji et al, 2018 (455)	Randomized, double-blind, placebo-controlled trial	60 participants	60 individuals with PD (aged 50-90 yrs), randomly distributed into two groups in order to take either probiotic or placebo (n = 30 each group)	Probiotic comprised of Bifidobacterium bifidum, Lactobacillus acidophilus, L. reuteri, and L. fermentum	12 wks	Improvement of the Movement Disorder Society-Unified Parkinson’s Disease rating scale, and insulin metabolism.
Georgescu et al, 2016  (456)	Randomized, placebo-controlled, double-blind trial	40 participants	40 PD patients (17 males, 23 females; mean age 76.05 ± 2.09 yrs) randomly divided into two groups in order to take either probiotics or trimebutine 200 mg	Lactobacillus acidophilus and Bifidobacterium infantis	3 mo	Ameliorated the symptoms of bloating and abdominal pain.
Synbiotics
Barichella et al, 2016  (396)	Tertiary setting, single center, double-blind, randomized, placebo-controlled trial	80 participants	Subjects with PD randomly divided into two classes, supplemented with fermented milk, including multiple probiotic strains and prebiotic fiber or placebo (a pasteurized, fermented, fiber-free milk)	Lactobacillus rhamnosus GG, L. acidophilus, L. plantarum, L. paracasei, L. delbrueckii subsp. bulgaricus, and Bifidobacterium (fermented milk), Streptococcus salivarius subsp. thermophilus, Enterococcus faecium	4 wks	Consumption of fermented milk was better than placebo in alleviating constipation in PD patients.