Exploring the Gut-Brain Axis and Connectome Architecture in Dementia Through Multimodal Correlation Imaging

Year

2025

Principal Investigator

Location

Italy, IT

Abstract

This project investigates neurodegenerative diseases through the novel lens of the intestinal connectome. We aim to establish causal relationships between gut neural networks and cognitive decline using multimodal imaging integration—combining advanced X-ray Phase Contrast Tomography with high-resolution Scanning Electron Microscopy. Our approach challenges traditional brain-centric views of dementia by mapping the "second brain" connectome, potentially revealing fundamental mechanisms underlying neurodegeneration. We employ cutting-edge iamging technologies to create 3D reconstructions of neural, immune, and microbial interactions within the gut-brain axis at micro/nanometric resolution, complemented by AI-powered data analysis. By identifying signature patterns of gut-brain dysregulation specific to neurodegenerative diseases, we'll establish new biomarkers and innovative therapeutic targets. This paradigm-shifting framework promises to transform clinical approaches to dementia through interventions targeting the intestinal-cerebral communication pathways.

Objectives

Objective 1 - Map structural alterations in the intestinal architecture - Characterize microscale and nanoscale changes in intestinal tissue morphology, epithelial barrier integrity, and vascular networks in Alzheimer's patients compared to healthy controls using high-resolution imaging.
Objective 2 - Establish the intestinal connectome in relation to neurodegeneration - Develop comprehensive 3D models of enteric neural networks, identifying specific alterations in neural, immune, and microbial interactions that correlate with cognitive decline.
Objective 3 – Identify causal pathways in the gut-brain axis - Determine mechanistic links between intestinal structural changes and cerebral pathology, validating potential biomarkers and therapeutic targets that could modulate neurodegeneration through intestinal intervention.

Collaborators

Key 5 publications

1. Investigating gut alterations in Alzheimer’s disease: In-depth analysis with micro-and nano- 3D X-ray phase contrast tomography, F Palermo et al; Science Advances 11 (5), eadr8511 (2025).
2. The Study of the Caudal Vertebrae of Thick-Toed Geckos after a Prolonged Space Flight by X-ray Phase-Contrast Micro-CT, I Bukreeva, et al; Cells 12 (19), 2415 (2023).
3. Multilevel X-ray imaging approach to assess the sequential evolution of multi-organ damage in multiple sclerosis, F Palermo, et al; Communications Physics 5 (1), 290 (2022).
4. Hydroxycarboxylic acid receptor 2, a pleiotropically linked receptor for the multiple sclerosis drug, monomethyl fumarate. Possible implications for the inflammatory response B Parodi et al; Frontiers in Immunology 12, 655212 (2021).