Lipid-mediated brain–gut axis alterations in functional diarrhea and their role in oxidative stress and neurodegeneration

Lipid mediators control intestinal motility, epithelial signalling, and neuronal function by integrating metabolic, hormonal, and neurological interactions throughout the brain-gut axis. Recurrent loose stools without structural abnormalities are the hallmark of Functional Diarrhoea (FD), a condition marked by high oxidative stress and disruptions in this axis. The main aim of this work is to further understand the role of lipid profiles in oxidative stress and neurological abnormalities in FD using the proposed Lipid-Mediated Brain-Gut Axis (LIMBRA) model. The LIMBRA system analyzes lipid abnormalities using targeted blood and faecal lipidomics with oxidative stress and cognitive assessment. FD showed mild cognitive impairment, high oxidative stress, increased lipid peroxidation, and reduced omega-3 anti-inflammatory mediators. These findings support a lipid-based mechanism linking gastrointestinal dysregulation to brain oxidative stress and neurodegeneration, providing a foundation for future studies on lipid biomarkers and therapies for FD and related cognitive disorders.