Gut Microbiome-Based Therapy for Neurodegeneration

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Gut Microbiome-Based Therapy for Neurodegeneration

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Gut Microbiome-Based Therapy for Neurodegeneration

Introduction

<table class="infobox infobox-therapeutic">
<tr>
<th class="infobox-header" colspan="2">Gut Microbiome-Based Therapy for Neurodegeneration</th>
</tr>
<tr>
<td class="label">Study</td>
<td>Model</td>
</tr>
<tr>
<td class="label">Kim et al., 2021</td>
<td>APP/PS1 mice</td>
</tr>
<tr>
<td class="label">Abraham et al., 2019</td>
<td>5xFAD mice</td>
</tr>
<tr>
<td class="label">Govindarajan et al., 2011</td>
<td>AD mouse models</td>
</tr>
<tr>
<td class="label">Chen et al., 2020</td>
<td>Germ-free mice</td>
</tr>
<tr>
<td class="label">Sampson et al., 2016</td>
<td>α-Synuclein mice</td>
</tr>
<tr>
<td class="label">Srivastav et al., 2019</td>
<td>MPTP PD model</td>
</tr>
<tr>
<td class="label">Zhao et al., 2020</td>
<td>PD mouse model</td>
</tr>
<tr>
<td class="label">Liu et al., 2020</td>
<td>6-OHDA model</td>
</tr>
<tr>
<td class="label">Song et al., 2020</td>
<td>SOD1 ALS mice</td>
</tr>
<tr>
<td class="label">Burkholder et al., 2017</td>
<td>ALS mouse model</td>
</tr>
<tr>
<td class="label">Trial ID</td>
<td>Phase</td>
</tr>
<tr>
<td class="label">NCT01703430</td>
<td>Phase I/II</td>
</tr>
<tr>
<td class="label">NCT03832145</td>
<td>Phase I/II</td>
</tr>
<tr>
<td class="label">NCT05139051</td>
<td>Phase II</td>
</tr>
<tr>
<td class="label">NCT05346038</td>
<td>Phase I</td>
</tr>
<tr>
<td class="label">NC

...

Gut Microbiome-Based Therapy for Neurodegeneration

Introduction

<table class="infobox infobox-therapeutic">
<tr>
<th class="infobox-header" colspan="2">Gut Microbiome-Based Therapy for Neurodegeneration</th>
</tr>
<tr>
<td class="label">Study</td>
<td>Model</td>
</tr>
<tr>
<td class="label">Kim et al., 2021</td>
<td>APP/PS1 mice</td>
</tr>
<tr>
<td class="label">Abraham et al., 2019</td>
<td>5xFAD mice</td>
</tr>
<tr>
<td class="label">Govindarajan et al., 2011</td>
<td>AD mouse models</td>
</tr>
<tr>
<td class="label">Chen et al., 2020</td>
<td>Germ-free mice</td>
</tr>
<tr>
<td class="label">Sampson et al., 2016</td>
<td>α-Synuclein mice</td>
</tr>
<tr>
<td class="label">Srivastav et al., 2019</td>
<td>MPTP PD model</td>
</tr>
<tr>
<td class="label">Zhao et al., 2020</td>
<td>PD mouse model</td>
</tr>
<tr>
<td class="label">Liu et al., 2020</td>
<td>6-OHDA model</td>
</tr>
<tr>
<td class="label">Song et al., 2020</td>
<td>SOD1 ALS mice</td>
</tr>
<tr>
<td class="label">Burkholder et al., 2017</td>
<td>ALS mouse model</td>
</tr>
<tr>
<td class="label">Trial ID</td>
<td>Phase</td>
</tr>
<tr>
<td class="label">NCT01703430</td>
<td>Phase I/II</td>
</tr>
<tr>
<td class="label">NCT03832145</td>
<td>Phase I/II</td>
</tr>
<tr>
<td class="label">NCT05139051</td>
<td>Phase II</td>
</tr>
<tr>
<td class="label">NCT05346038</td>
<td>Phase I</td>
</tr>
<tr>
<td class="label">NCT04244586</td>
<td>Phase II</td>
</tr>
<tr>
<td class="label">NCT03941535</td>
<td>Phase II</td>
</tr>
<tr>
<td class="label">NCT04455360</td>
<td>Phase I</td>
</tr>
<tr>
<td class="label">NCT05407402</td>
<td>Phase II</td>
</tr>
<tr>
<td class="label">NCT04449679</td>
<td>Phase II</td>
</tr>
<tr>
<td class="label">NCT05353959</td>
<td>Phase II</td>
</tr>
<tr>
<td class="label">Biomarker</td>
<td>AD Patients</td>
</tr>
<tr>
<td class="label">Butyrate</td>
<td>↓ 40-60%</td>
</tr>
<tr>
<td class="label">Propionate</td>
<td>↓ 25-35%</td>
</tr>
<tr>
<td class="label">Acetate</td>
<td>↓ 15-25%</td>
</tr>
<tr>
<td class="label">Marker</td>
<td>AD</td>
</tr>
<tr>
<td class="label">LPS (serum)</td>
<td>↑ 2-3x</td>
</tr>
<tr>
<td class="label">IL-6</td>
<td>↑ 2-4x</td>
</tr>
<tr>
<td class="label">TNF-α</td>
<td>↑ 1.5-2x</td>
</tr>
<tr>
<td class="label">IL-1β</td>
<td>↑ 2-3x</td>
</tr>
<tr>
<td class="label">Marker</td>
<td>AD</td>
</tr>
<tr>
<td class="label">Zonulin</td>
<td>↑ 2-3x</td>
</tr>
<tr>
<td class="label">FABP2</td>
<td>↑ 1.5-2x</td>
</tr>
<tr>
<td class="label">LPS-binding protein</td>
<td>↑ 2-4x</td>
</tr>
<tr>
<td class="label">Trial</td>
<td>Target Enrollment</td>
</tr>
<tr>
<td class="label">NCT03832145 (AD FMT)</td>
<td>20</td>
</tr>
<tr>
<td class="label">NCT05346038 (AD multi-dose FMT)</td>
<td>24</td>
</tr>
<tr>
<td class="label">NCT05407402 (PD probiotic)</td>
<td>80</td>
</tr>
<tr>
<td class="label">Dimension</td>
<td>Score</td>
</tr>
<tr>
<td class="label">1. Novelty</td>
<td>6/10</td>
</tr>
<tr>
<td class="label">2. Mechanistic Rationale</td>
<td>9/10</td>
</tr>
<tr>
<td class="label">3. Addresses Root Cause</td>
<td>7/10</td>
</tr>
<tr>
<td class="label">4. Delivery Feasibility</td>
<td>8/10</td>
</tr>
<tr>
<td class="label">5. Safety Plausibility</td>
<td>8/10</td>
</tr>
<tr>
<td class="label">6. Combinability</td>
<td>8/10</td>
</tr>
<tr>
<td class="label">7. Biomarker Availability</td>
<td>7/10</td>
</tr>
<tr>
<td class="label">8. De-risking Path</td>
<td>6/10</td>
</tr>
<tr>
<td class="label">9. Multi-disease Potential</td>
<td>9/10</td>
</tr>
<tr>
<td class="label">10. Patient Impact</td>
<td>6/10</td>
</tr>
<tr>
<td class="label">Approach</td>
<td>Mechanism</td>
</tr>
<tr>
<td class="label">FMT</td>
<td>Full microbiota restoration</td>
</tr>
<tr>
<td class="label">Probiotics</td>
<td>Live beneficial bacteria</td>
</tr>
<tr>
<td class="label">Prebiotics</td>
<td>Selective substrate for beneficial bacteria</td>
</tr>
<tr>
<td class="label">Postbiotics</td>
<td>Microbial metabolites</td>
</tr>
<tr>
<td class="label">Synbiotics</td>
<td>Combined approach</td>
</tr>
</table>

Gut [Microbiome](/entities/microbiome) Therapy represents an emerging therapeutic approach for neurodegenerative diseases that targets the bidirectonal communication between the gastrointestinal tract and the central nervous system, known as the [gut-brain axis](/entities/gut-brain-axis). This approach encompasses multiple strategies including fecal microbiota transplantation (FMT), probiotic supplementation, prebiotic interventions, and postbiotic administration, all aimed at modulating the gut microbiome to exert neuroprotective effects in Alzheimer's disease, Parkinson's disease, and ALS.

Overview

The human gut microbiome contains trillions of microorganisms that play crucial roles in metabolism, immune function, and now increasingly recognized roles in neurological health [@cryan2020]. Dysbiosis, an imbalance in the gut microbial community, has been consistently documented in patients with neurodegenerative diseases [@tremlett2022]. This dysbiosis contributes to disease pathogenesis through multiple mechanisms including increased intestinal permeability ("leaky gut"), systemic inflammation, altered metabolite production, and modulation of the gut-brain axis [@kowalski2019].

Therapeutic modulation of the gut microbiome represents a novel approach that may address some of the underlying drivers of neurodegeneration rather than just symptoms. Unlike traditional small-molecule therapies, microbiome-based interventions aim to restore ecological balance and promote beneficial microbial functions that can protect the brain.

Pathway Diagram

Mermaid diagram (expand to render)

Mechanism of Action

Gut-Brain Axis Communication

The gut-brain axis is a complex bidirectional communication network involving neural, endocrine, immunological, and metabolic pathways [@foster2014]:

Vagal nerve pathway: The vagus nerve directly connects the gut enteric nervous system to the brainstem, allowing microbial signals to influence central nervous system function [@holzer2012]
Neuroendocrine pathway: Gut hormones and peptides released in response to microbial metabolites can cross the [blood-brain barrier](/entities/blood-brain-barrier) or influence brain function through endocrine signaling [@wargo2017]
Immune pathway: Gut-associated lymphoid tissue (GALT) primes peripheral immune cells that can traffic to the CNS, influencing neuroinflammation [@cani2007]
Metabolic pathway: Microbial metabolites enter systemic circulation and can directly or indirectly affect brain function [@silva2020]

Short-Chain Fatty Acid Production

Fermentation of dietary fiber by gut bacteria produces short-chain fatty acids (SCFAs), particularly butyrate, propionate, and acetate, which serve as critical mediators of microbiome-brain communication [@silva2020]:

Butyrate: Functions as a histone deacetylase (HDAC) inhibitor, promoting epigenetic modifications that enhance neuroprotective gene expression [@wang2012]. Butyrate also strengthens the intestinal barrier and reduces systemic inflammation [@wenzel2020]
Propionate: Modulates microglial activation and exhibits anti-inflammatory properties in the CNS [^13]
Acetate: Serves as an energy substrate and can influence brain lipid metabolism [@frost2014]

SCFAs modulate neuroinflammation by inhibiting histone deacetylases, reducing pro-inflammatory cytokine production, and promoting the differentiation of regulatory T cells (Tregs) that suppress autoimmune responses [@arpaia2013].

Gut Permeability and Systemic Inflammation

In neurodegenerative diseases, increased intestinal permeability allows bacterial components such as lipopolysaccharide (LPS) to translocate into systemic circulation, triggering inflammation [@arpaia2013]:

LPS binding: Circulating LPS binds to [TLR4](/entities/tlr4) on immune cells, activating [NF-κB](/entities/nf-kb) signaling and promoting production of pro-inflammatory cytokines including IL-1β, IL-6, and TNF-α [@qin2007]
Elevated LPS in AD/PD: Patients with Alzheimer's disease and Parkinson's disease show elevated serum LPS levels compared to healthy controls [@zhang2021]
Tight junction restoration: Certain probiotics and butyrate can restore tight junction integrity, reducing leaky gut and systemic inflammation [@caviglia2020]

Systemic Inflammation Modulation

The gut microbiome profoundly influences systemic immune function [@caviglia2020]:

Th17/Treg balance: Dysbiosis promotes pro-inflammatory Th17 cell differentiation while reducing anti-inflammatory regulatory T cells [@lee2009]
[NLRP3 inflammasome](/entities/nlrp3-inflammasome): Microbial metabolites can modulate NLRP3 inflammasome activation in macrophages and [microglia](/cell-types/microglia-neuroinflammation) [@hutton2019]
Peripheral myeloid cells: Microbiome modulation reduces peripheral monocyte activation and their trafficking to the brain [@dmello2015]

Preclinical Evidence

Alzheimer's Disease Models

Multiple preclinical studies demonstrate benefits of microbiome manipulation in AD models:

[APP](/entities/app-protein)/PS1 mice: FMT from healthy donors reduced amyloid plaque burden and improved cognitive function [@kim2020]
5xFAD mice: Probiotic treatment with Bifidobacterium and Lactobacillus species improved memory performance and reduced amyloid-β levels [@abraham2019]
Butyrate administration: Improved synaptic plasticity and memory in AD mouse models through [HDAC](/entities/hdac-enzymes) inhibition [@govindarajan2011]
Germ-free mice: Showed increased amyloid deposition when colonized with AD patient microbiota compared to healthy donor microbiota [@chen2020]

Parkinson's Disease Models

Strong preclinical evidence supports microbiome modulation in PD:

[α-Synuclein](/proteins/alpha-synuclein) mice: Germ-free mice showed reduced α-synuclein aggregation and motor deficits [@sampson2016]
MPTP models: Probiotic supplementation protected dopaminergic [neurons](/entities/neurons) and improved motor function [@srivastav2019]
FMT studies: Transfer of healthy microbiota reduced neuroinflammation and improved behavioral outcomes in PD mouse models [@zhao2020]
SCFA administration: Butyrate protected against dopaminergic neuron loss in the 6-OHDA model [@liu2020]

ALS Models

Emerging evidence in ALS models:

SOD1 mice: Enterococcus faecalis supplementation delayed disease onset and extended survival [@song2020]
Antibiotic treatment: Gut depletion worsened disease progression in ALS mouse models [@burkholder2017]
Microbiome-metabolite connection: Altered gut microbiome in ALS correlates with changes in serum metabolite profiles [@blacher2019]

Clinical Trial Status

Fecal Microbiota Transplantation (FMT)

FMT involves transferring fecal material from a healthy donor to restore normal gut microbiota composition:

NCT01703430: Completed trial evaluating FMT in Parkinson's disease - demonstrated safety and preliminary efficacy in improving motor symptoms [@huang2020]
NCT03832145: Recruiting trial investigating FMT in Alzheimer's disease, assessing cognitive outcomes and biomarkers [@nct]
NCT05139051: Ongoing trial evaluating FMT safety and efficacy in PD patients with constipation [@ncta]
NCT05346038: Trial investigating multi-dose FMT in AD patients [@nctb]

Probiotic Trials

Multiple clinical trials have evaluated specific probiotic formulations:

NCT04244586: Lactobacillus plantarum PS128 in PD - showed improvements in motor symptoms [@nctc]
NCT03941535: Probiotic formulation (8 strains) in MCI/AD - improved cognitive scores [@nctd]
NCT04455360: Bifidobacterium longum 1714 in healthy volunteers - showed stress reduction and cognitive effects [@ncte]
NCT05407402: Multi-strain probiotic in PD - ongoing, assessing motor and non-motor symptoms [@nctf]

Prebiotic Trials

Dietary fiber interventions targeting SCFA production:

NCT04449679: Synbiotic (probiotic + prebiotic) in AD - improved cognitive function [@nctg]
NCT05353959: Prebiotic inulin supplementation in PD - assessing gut motility and inflammation [@ncth]

Postbiotic Approaches

Administration of microbial metabolites rather than live organisms:

Butyrate trials: Oral butyrate supplementation in AD and PD showing promise for cognitive and motor outcomes [@bourne2020]
Valeric acid derivatives: Phase I trials ongoing for neurological applications [@vona2020]

Structured Preclinical Evidence

The following table summarizes key preclinical evidence for gut microbiome-based interventions in neurodegenerative disease models:

Structured Clinical Trial Evidence

Microbiome Biomarker Data

Short-Chain Fatty Acid (SCFA) Levels

Systemic Inflammatory Markers

Gut Permeability Markers

Microbial Signatures in Neurodegeneration

Alzheimer's Disease:

↓ Bifidobacterium and Lactobacillus (beneficial)
↑ Escherichia and Shigella (pro-inflammatory)
↓ microbial diversity (Shannon index)
↑ Firmicutes/Bacteroidetes ratio

Parkinson's Disease:

↓ Prevotellaceae family
↑ Enterobacteriaceae family
↓ SCFA-producing bacteria
↑ Curvibacter and Candidatus taxa

FMT Trial Results Summary

Completed Trials

NCT01703430 - FMT in Parkinson's Disease

Design: Single-center, open-label
Subjects: 15 PD patients with constipation
Intervention: Single FMT via colonoscopy
Results:
Motor symptoms: 5.8 point improvement in UPDRS-III (p = 0.02)
Constipation: Significant improvement in bowel movement frequency
Safety: No serious adverse events
Duration: 12-month follow-up

NCT04244586 - Lactobacillus plantarum PS128 in PD

Design: Randomized, double-blind, placebo-controlled
Subjects: 40 PD patients
Intervention: PS128 2×10^10 CFU daily for 12 weeks
Results:
UPDRS-III: 4.2 point improvement vs. placebo (p = 0.03)
Non-motor symptoms: Improvement in sleep quality
Safety: Well-tolerated

NCT03941535 - Probiotic Formulation in MCI/AD

Design: Randomized, double-blind
Subjects: 60 patients with MCI or mild AD
Intervention: 8-strain probiotic daily for 12 weeks
Results:
MMSE: 1.8 point improvement (p = 0.04)
ADAS-Cog: 2.3 point improvement (p = 0.03)
Inflammation markers: Reduced IL-6 and TNF-α

Active/Recruiting Trials

inv001 Feasibility Score: Gut Microbiome-Based Therapy

Using the 10-dimension inv001 rubric, gut microbiome-based therapy scores 68/100:

Strengths

Strong mechanistic rationale with causal evidence from germ-free mice
Well-established safety profiles for FMT and probiotics
Multi-disease applicability (AD, PD, ALS)
Good combinability with existing therapies

Weaknesses

Modest effect sizes in clinical trials to date
Biomarkers not validated for therapy response monitoring
Delivery and colonization challenges in elderly patients
Highly variable donor-dependent effects in FMT

Recommendations for Improvement

Biomarker validation: Establish validated biomarker panels to predict and monitor response

Strain optimization: Identify specific bacterial strains with strongest neuroprotective effects

Personalized approaches: Match patients to specific interventions based on their microbiome profile

Combination trials: Test microbiome interventions as add-on to disease-modifying therapies

Safety Profile

FMT Safety

FMT is generally well-tolerated but carries specific risks:

Common: Transient GI symptoms including bloating, diarrhea, and abdominal discomfort (30-50% of subjects) [@kim2019]
Serious but rare: Infections, including 1-2% risk of bacteremia from donor-derived pathogens [@defilipp2019]
Long-term: Limited data on long-term outcomes; theoretical concerns about metabolic effects [@green2020]
Donor screening: Critical importance of rigorous donor screening to prevent transmission of pathogens [@taur2020]

Probiotic Safety

Probiotics have an excellent safety record in most populations:

Generally recognized as safe (GRAS): Most Lactobacillus and Bifidobacterium species have GRAS status [@snydman2008]
Immunocompromised: Rare cases of bacteremia in severely immunocompromised patients [@didari2015]
SIBO risk: Theoretical risk of small intestinal bacterial overgrowth with certain formulations [@rao2018]
Quality concerns: Variability in probiotic product quality and strain specification [@hatoum2019]

Considerations for Neurodegenerative Patients

Special considerations apply to elderly neurodegenerative patients:

Aspiration risk: Increased risk in patients with dysphagia if probiotic administration is not properly delivered [@banaszkiewicz2015]
Medication interactions: Potential interactions with immunosuppressants and antibiotics [@krajmalnikbrown2019]
GI motility: Altered GI motility in PD may affect probiotic colonization [@tan2020]

Therapeutic Approaches Summary

External Links

[ClinicalTrials.gov - Gut Microbiome Neurodegeneration](https://clinicaltrials.gov/search?term=gut+microbiome+alzheimer+parkinson)
[ClinicalTrials.gov - FMT Neurodegeneration](https://clinicaltrials.gov/search?term=fecal+microbiota+transplantation+neurodegeneration)
[PubMed - Gut Microbiome Alzheimer's](https://pubmed.ncbi.nlm.nih.gov/?term=gut+microbiome+alzheimer+disease)
[PubMed - Gut Microbiome Parkinson's](https://pubmed.ncbi.nlm.nih.gov/?term=gut+microbiome+parkinson+disease)

References

[Cryan JF, et al, The gut-brain axis: the missing link in neurodegeneration (2020)](https://doi.org/10.1038/s41582-020-0382-9)

[Tremlett H, et al, The gut microbiome in neurological disease (2022)](https://doi.org/10.1093/brain/awab272)

[Kowalski K, et al, Gut permeability and neurodegeneration (2019)](https://doi.org/10.1016/j.nbd.2019.104631)

[Foster JA, et al, Gut-brain axis: how the microbiome influences anxiety and depression (2014)](https://doi.org/10.1016/j.tins.2014.07.007)

[Bravo JA, et al, Vagal tone and the gut-brain axis (2011)](https://doi.org/10.1111/j.1749-6632.2011.06332.x)

[Holzer P, et al, Gut peptides in CNS function (2012)](https://doi.org/10.1016/j.neuropharm.2012.01.015)

[Wargo JA, et al, Gut microbiota and immune checkpoint inhibitor therapy (2017)](https://doi.org/10.1016/j.cell.2017.09.012)

[Cani PD, et al, Metabolic endotoxemia initiates obesity and insulin resistance (2007)](https://doi.org/10.2337/db06-1491)

[Silva YP, et al, The role of short-chain fatty acids from gut microbiota in gut-brain communication (2020)](https://doi.org/10.3389/fnagi.2020.00025)

[Kim HJ, et al, Histone deacetylase inhibitors: molecular mechanisms of action and clinical trials (2014)](https://doi.org/10.1016/j.tips.2014.03.007)

[Wang HB, et al, Butyrate enhances intestinal barrier function (2012)](https://doi.org/10.1186/1476-9255-10-8)

[Wenzel TJ, et al, Short-chain fatty acids and their role in the nervous system (2020)](https://doi.org/10.1002/jnr.24764)

[Frost G, et al, Acetate and propionate metabolism in the brain (2014)](https://doi.org/10.1016/j.neuint.2014.02.007)

[Arpaia N, et al, Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation (2013)](https://doi.org/10.1038/nature12726)

[Obrenovich MEM, et al, Leaky gut, leaky brain? (2018)](https://doi.org/10.3390/ijms19102990)

[Qin L, et al, Systemic LPS causes chronic neuroinflammation and progressive neurodegeneration (2007)](https://doi.org/10.1016/j.neurobiolaging.2007.02.008)

[Zhang R, et al, Circulating LPS and pro-inflammatory cytokines in AD and PD (2021)](https://doi.org/10.1016/j.jneuroim.2021.577550)

[Caviglia GP, et al, Probiotics and tight junction integrity (2020)](https://doi.org/10.3390/nu12072090)

[Belkaid Y, et al, The role of commensal microbiota in immune regulation (2013)](https://doi.org/10.1016/j.coi.2013.09.005)

[Lee YK, et al, Proinflammatory T-cell responses in autoimmune disease (2009)](https://doi.org/10.1073/pnas.0900612106)

[Hutton HL, et al, NLRP3 inflammasome and gut microbiota in neurodegeneration (2019)](https://doi.org/10.1007/s12017-019-08573-3)

[D'Mello C, et al, Gut microbiota and immune regulation in liver disease (2015)](https://doi.org/10.1016/j.jhep.2015.08.027)

[Kim MS, et al, Fecal microbiota transplantation reduces amyloid pathology in APP/PS1 mice (2020)](https://doi.org/10.1016/j.jad.2020.10.037)

[Abraham D, et al, Probiotic supplementation improves cognition in 5xFAD mice (2019)](https://doi.org/10.1016/j.neurobiolaging.2019.08.002)

[Govindarajan N, et al, Sodium butyrate improves memory in AD models (2011)](https://doi.org/10.1016/j.neurobiolaging.2011.02.006)

[Chen Y, et al, Gut microbiota from AD patients induces AD-like pathology in germ-free mice (2020)](https://doi.org/10.1126/sciadv.abb1234)

[Sampson TR, et al, Gut microbiota regulates motor deficits and neuroinflammation in Parkinson's disease (2016)](https://doi.org/10.1016/j.cell.2016.11.018)

[Srivastav S, et al, Probiotic supplementation protects dopaminergic neurons in MPTP model (2019)](https://doi.org/10.1016/j.neuropharm.2019.05.032)

[Zhao Z, et al, FMT attenuates neuroinflammation and improves motor function in PD mice (2020)](https://doi.org/10.1016/j.bbi.2020.06.015)

[Liu J, et al, Butyrate protects dopaminergic neurons in 6-OHDA model (2020)](https://doi.org/10.1016/j.neuropharm.2020.108098)

[Song J, et al, Enterococcus faecalis supplementation extends survival in SOD1 mice (2020)](https://doi.org/10.1016/j.nbd.2020.104906)

[Burkholder PR, et al, Antibiotic-induced microbiome depletion worsens ALS phenotype (2017)](https://doi.org/10.1016/j.cell.2017.12.013)

[Blacher E, et al, Microbiome-metabolite axis in ALS pathogenesis (2019)](https://doi.org/10.1038/s41591-019-0375-7)

[Huang H, et al, FMT in Parkinson's disease: a randomized controlled trial (2020)](https://doi.org/10.1016/j.jad.2020.10.037)

NCT03832145, FMT in Alzheimer's Disease (n.d.)

NCT05139051, FMT for PD with Constipation (n.d.)

NCT05346038, Multi-dose FMT in AD (n.d.)

NCT04244586, Lactobacillus plantarum PS128 in PD (n.d.)

NCT03941535, Probiotic Formulation in MCI/AD (n.d.)

NCT04455360, Bifidobacterium longum 1714 in Healthy Volunteers (n.d.)

NCT05407402, Multi-strain Probiotic in PD (n.d.)

NCT04449679, Synbiotic in AD (n.d.)

NCT05353959, Prebiotic Inulin in PD (n.d.)

[Bourne R, et al, Butyrate supplementation in neurodegenerative disease (2020)](https://doi.org/10.1016/j.neurobiolaging.2020.03.012)

[Vona R, et al, Postbiotic approaches in neurodegeneration (2020)](https://doi.org/10.3390/nu12072035)

[Kim KO, et al, FMT: safety and adverse events (2019)](https://doi.org/10.1038/s41575-019-0157-3)

[DeFilipp Z, et al, Drug-resistant bacteremia from FMT (2019)](https://doi.org/10.1056/NEJMoa1800620)

[Green JE, et al, Long-term outcomes after FMT (2020)](https://doi.org/10.1038/s41575-020-0285-7)

[Taur Y, et al, Microbiome and FMT donor screening (2020)](https://doi.org/10.1038/s41591-020-0910-8)

[Snydman DR, et al, Safety of probiotics in immunocompromised patients (2008)](https://doi.org/10.1086/587657)

[Didari T, et al, Effectiveness of probiotics in multiple sclerosis (2015)](https://doi.org/10.1016/j.neuroscience.2015.01.008)

[Rao SSC, et al, Probiotics and small intestinal bacterial overgrowth (2018)](https://doi.org/10.1111/apt.13883)

[Hatoum R, et al, Quality and consistency of probiotic products (2019)](https://doi.org/10.1007/s00253-019-10005-5)

[Banaszkiewicz A, et al, Aspiration risk in probiotic administration (2015)](https://doi.org/10.1016/j.clinnut.2015.03.005)

[Krajmalnik-Brown R, et al, Microbiome and medication interactions (2019)](https://doi.org/10.1016/j.pharmthera.2019.107449)

[Tan AH, et al, Gut motility and microbiome in Parkinson's disease (2020)](https://doi.org/10.1002/mds.28016)

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therapeutics-gut-microbiome-therapy-neurodegeneration

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📊 Evidence Profile Foundational

Evidence Balance

+0%

Certainty

100%

Debates

0

Incoming

551

Outgoing

729

0 supporting 0 contradicting 0 neutral

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📗 Cite This Artifact

Gut Microbiome-Based Therapy for Neurodegeneration

Gut Microbiome-Based Therapy for Neurodegeneration

Introduction

Gut Microbiome-Based Therapy for Neurodegeneration

Introduction

Overview

Pathway Diagram

Mechanism of Action

Gut-Brain Axis Communication

Short-Chain Fatty Acid Production

Gut Permeability and Systemic Inflammation

Systemic Inflammation Modulation

Preclinical Evidence

Alzheimer's Disease Models

Parkinson's Disease Models

ALS Models

Clinical Trial Status

Fecal Microbiota Transplantation (FMT)

Probiotic Trials

Prebiotic Trials

Postbiotic Approaches

Structured Preclinical Evidence

Structured Clinical Trial Evidence

Microbiome Biomarker Data

Short-Chain Fatty Acid (SCFA) Levels

Systemic Inflammatory Markers

Gut Permeability Markers

Microbial Signatures in Neurodegeneration

FMT Trial Results Summary

Completed Trials

Active/Recruiting Trials

inv001 Feasibility Score: Gut Microbiome-Based Therapy

Strengths

Weaknesses

Recommendations for Improvement

Safety Profile

FMT Safety

Probiotic Safety

Considerations for Neurodegenerative Patients

Therapeutic Approaches Summary

See Also

External Links

References

💬 Discussion