## 5 Microbiome Modification as a Therapeutic Target for Neurodegenerative Diseases
### Prebiotics
#### 5.1.2 Effects of Prebiotics on the Microbiome Modification  
In a randomized, double-blind, placebo-controlled, three-period, cross-over trial, 29 healthy adults 20-40 years old received 0, 5.0, or 7.5 g of _Agave inulin_/day for 21 days. This in vitro study proved that _Agave inulin_ is fermented by _Bifidobacterium_ and _Lactobacillus_. _Fecal actinobacteria_ and _Bifidobacterium_ increased 3- and 4-fold after 5.0 and 7.5 g of _Agave inulin_/d, respectively, in comparison to the control, while Desulfovibrio was diminished by 40% with _Agave inulin_ compared to the control. Dietary fiber consumption was related to fecal butyrate, tended to be related to _Bifidobacterium_, and was negatively associated with Desulfovibrio abundance. Four species in the _Bifidobacterium genera_ were highly increased after the intake of 5.0 and 7.5 g _Agave inulin_/d compared with the control: _B. adolescentis_, _B. breve_, _B. longum_, and _B. pseudolongum_[48]. In another open-label, non-randomized study, the participants affected by PD consumed prebiotics for 10 days. This intervention reduced the pro-inflammatory phyla _Proteobacteria_ and _Escherichia coli_ and increased SCFA-producing species like _Fusicatenibacterium saccharivorans_ and _Parobacteroides merade_, _Bifidobacterium adolescentis_, _Facellibacterium prausnitzii_, and _Ruminococcus bicirculans_, with a simultaneous increase in plasma SCFA. The prebiotic intervention also diminished plasma zonulin, a marker of intestinal barrier integrity, and calprotectin, a marker of neutrophils in the intestinal mucosa [51]. A randomized, double-blind, placebo-controlled, cross-over study included 34 healthy participants 19-65 years old, divided into two groups: low dietary fiber (LDF) and high dietary fiber (HDF) consumers. After 3 weeks of daily prebiotic consumption or a placebo, gut microbiota constitution (16S rRNA bacterial gene-sequencing) and SCFA concentrations were investigated. The aim of this study was to examine whether LDF versus HDF consumption modifies the gut microbiota reaction to an insulin-type fructan prebiotic. In the LDF group, the prebiotic consumption increased _Bifidobacterium_. In the HDF group, the prebiotic consumption increased _Bifidobacterium_ and _Facellibacterium_ and diminished _Ruminococcus_, _Dorea_, and _Coprococcus_. This study found that HDF consumers had a higher gut microbiota reaction and a greater benefit from the insulin-type fructan prebiotic compared to LDF consumers [50]. In a double-blind, placebo-controlled clinical trial, 35 sedentary constipationed adults were given 10 g GOS and sugar gummies for 30 days. The aim of the study was to investigate the effect of GOS gummy consumption on gut health and depression in constipationed subjects. After 30 days of GOS consumption, increased _Lactobacillus_, _Bifidobacterium_, and _Bacteroides_ considerably diminished the phyla _Bacteroides_, _Firmicutes_, and the genus _Clostridium_. The _Firmicutes_ to _Bacteroides_ (F/B) ratio was also ameliorated in the GOS group. The F/B ratio is an indicator of gut dysbiosis. GOS consumption ameliorated the SCFA profile. Increased levels of acetic acid, butyric acid, and propionic acid were found in the experimental group in comparison to the placebo. In conclusion, the daily consumption of 10 g of GOS for 30 days improves gut dysbiosis, constipation, and depression in subjects with functional constipation [49]. A cross-sectional study recruited 41 adult patients (25 males, 16 females) who were receiving exclusive enteral nutrition for at least 12 days. In total, 25 patients consumed FOS/fiber-enriched formulae, and 16 patients consumed standard formulae (no fiber or FOS). Fluorescent in situ hybridization was utilized to examine fecal samples for the main groups of microbiatas, and gas-liquid chromatography was utilized to examine SCFAconcentrations. There were low concentrations of the main bacterial groups, including _Bifidobacteria_, in all patients.