Table 3 Clinical and animal models for testing various immunological and gut microbiota-based therapeutics
From: Beyond the gut: decoding the gut–immune–brain axis in health and disease
Disorder | Model | Axis | Therapeutic | Mechanism | Ref. |
|---|---|---|---|---|---|
Stroke, MS | Clinical | Immune | Fingolimod | Lymphocyte sequestration in the lymph nodes | [340] |
Stroke | Clinical | Immune | Anakinra | IL-1R antagonist | [341] |
Clinical | Immune | IL-2 AAV vector | Treg expansion | [343] | |
AD | Clinical | Immune | Aducanumab | N-terminal Aβ-targeting antibody | [346] |
Clinical | Immune | Lecanemab | Aβ protofibrils-targeting monoclonal antibody | [348] | |
Clinical | Immune | Donanemab | N-terminal truncated Aβ-targeting IgG | [347] | |
Clinical | Immune | Masitinib | Mast cell & microglia-targetting tyrosine kinase inhibitor | [349] | |
Clinical | Immune | PD-1/PD-L1 Blockade | PD-1 checkpoint blockade leads to IFN-γ-mediated recruitment of macrophages for Aβ clearance | [350] | |
APP/PS1 Mouse | Gut-Immune-Brain | L. paracasei D3.5, L. rhamnosus D4.4, L. plantarum D6.2, L. rhamnosus D7.5 and L. plantarum D13.4, E. raffinosus D24.1, E. INBio D24.2, E. avium D25.1, E. avium D25.2 and E. avium D26.1 | ↑ BBB and intestinal barrier integrity ↓ Microglial activation, IL-6, TNF-α | [370] | |
3xTg-AD Mouse | Gut-Immune-Brain | Lactobacillus plantarum KY1032 and Lactobacillus curvatus HY7601 | ↓ Microglia and astrocyte density ↑ Neuron density | [371] | |
PD | Clinical | Immune | Sargramostim | GM-CSF-induced DC enhancement for Treg induction | [353] |
Clinical | Immune | Azathioprine | Immunosuppressant that suppress lymphocyte proliferation | [354] | |
Clinical | Immune | AKST4290 | G protein-coupled C-C chemokine receptor type 3 antagonist | [355] | |
Clinical | Gut-Brain | L. paracasei DG and inulin fiber | ↑ Cognitive function, improved bowel function, altered microbiota composition | [372] | |
Clinical | Gut-Immune-Brain | L. rhamnosus, E. faecium, L. acidophilus, L. plantarum | ↓ TNF-α and IL-6 in plasma | [374] | |
MPTP-Mouse | Gut-Immune-Brain | L. rhamnosus E9 | Improve motor function by reducing ROS in brain and enhancing intestinal barrier integrity | [373] | |
Epilepsy | Clinical | Immune | Tocilizumab | IL-6 receptor inhibitor | [358] |
Clinical | Immune | Anakinra | Anti-IL-1 receptor antagonist | [359] | |
Clinical | Immune | Natalizumab | Anti-α4-integrin antibody | [360] | |
ASD | BTBR Mouse | Gut-Brain | C. butyricum | Enhancement of intestinal barrier function via SCFA and HDAC1 modulation | [365] |
PPA- Rat | Gut-Immune-Brain | L. rhamnosus and luteolin | ↓ TNF-α and IL-6 ↑ GABA, glutathione, glutathione peroxidase in brain | [366] | |
PPA-Rat | Gut-Immune-Brain | B. longum BB536 | ↑ Oxytocin ↓ IFN-γ | [367] | |
MIA Mouse | Gut-Immune-Brain | P. goldsteinii MTS01 | ↓ Colonic TNF-α, IL-6, IL-1β ↑ Antioxidant pathways and ↓ glutamate receptor signaling in brain | [368] | |
Depression | Chronic Stress Mouse | Gut-Immune-Brain | L. plantarum ATCC 793 (Lp793), B. longum ATCC 15707 (Bl15707), and botanical derived polyphenolic preparation | ↑ CTLA4+ Tregs ↓ Th17 in gut, IL-1β, IL-17a in serum, IL-1β in cortex | [376] |
Depression and Anxiety | LPS Mouse | Gut-Immune-Brain | L. lactis, L. cremoris, L. diacetylactis, L. acidophilus, and lactic yeasts | ↓ IL-12, TNF-α, IL-1β | [377] |
ADHD, ASD, Emotion Regulation | Clinical | Gut-Immune-Brain | Synbiotic 2000 | ↓ IL-12/IL-23p40, soluble intercellular adhesion molecule 1 ↑ Propionic Acid in blood | [378] |
