Targeting the Gut Dysbiosis to Treat Inflammation-driven Synaptopathy in MS

Summary

Inflammatory synaptopathy is a prominent pathogenic process in multiple sclerosis (MS) induced by imbalanced immune system homeostasis. Its persistence causes excitotoxic neuronal damage, leading to motor and cognitive deficits. Although many advances have been made in MS treatment, the development of effective strategies for managing disease progression driven by excitotoxic synaptic dysfunctions is of great significance. Gut dysbiosis is commonly associated with both MS and obesity and high-fat diet (HFD) can exacerbate disease by acting on gut microbiota.

Since gut microbiota can shape the immune response and brain functions, we propose to target gut dysbiosis by dietary supplementation of prebiotics and probiotics (Pre-Pro) to treat synaptopathy in both human and experimental model of MS, even when exacerbated by HFD. Overall, this project aims at unveiling the anti-inflammatory and neuroprotective pathways activated by Pre-Pro supplementation to modulate the immune-synaptic axis.

Conditions

• Patient Participation

Interventions

DIETARY_SUPPLEMENT

Prebiotics and Probiotics supplementation

From the 1st day to the 15th day (included) patients with MS in the Pre-Pro group will receive daily: 1 capsule of Probactiol Duo, Metagenics (6 billions of Saccharomyces boulardii and 8,5 billions of probiotics including Bifidobacterium lactis Bi-07®, Bifidobacterium lactis Bl-04, Lacticaseibacillus paracasei Lpc-37, Lactobacillus acidophilus NCFM®) 1. packet of Probactiol Stips, Metagenics (4 g inulin enriched with oligofructose) From the16th day to the 365th day (included) patients with MS in the Pre-Pro group will receive daily: 2. capsules of Probactiol HMO Combi, Metagenics (7,5 billions of Lactobacillus acidophilus NCFM®, 7,5 billions of Bifidobacterium lactis Bi-07®, 2,5 ug Vitamine D3, 320 ug Vitamine A, 100 mg Threonine, 250 mg 2'-Fucosyllactose).

DIETARY_SUPPLEMENT

Placebo supplementation

1-year supplementation with two placebo capsules/day containing starch, the probiotic bacteria carrier.

PROCEDURE

peripheral blood withdrawal

40 ml of blood for the isolation of Peripheral Blood Cells (PBMCs) and T cells.

PROCEDURE

Transcranial Magnetic Stimulation (TMS)

Intermittent theta burst stimulation (iTBS) protocol

Sponsors & Collaborators

• I.R.C.C.S. Fondazione Santa Lucia

  collaborator OTHER

• Neuromed IRCCS

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

65 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2023-07-26

Primary Completion

2024-11-02

Completion

2026-05-01

Countries

• Italy

Study Locations