To evaluate anti-oxidative and anti-inflammatory effects of butyrate on the transport of large neutral amino acids such as tryptophan, a precursor of the neurotransmitter serotonin, in in vitro models

These models consist of fibroblasts collected from healthy individuals and from patients with gastrointestinal diseases such as inflammatory bowel syndrome (IBS) and with well-known depression, mood and behavioural problems such as attention deficit hyperactivity disorder (ADHD) and autistic spectrum disorder patients. Fibroblast cells serve as convenient in vitro model to study different disorders, such as neuropsychiatric diseases. Fibroblasts express several neuronal specific enzymes and receptors, have the same expression pattern of amino acid transporters as human brain microvascular endothelial cells, can be easily obtained from patients and can be converted into functional neurons. Besides, the transport of tryptophan across the fibroblast cell membranes has already been characterized. The second in vitro model consists of Caco-2 cell monolayers; these are cells derived from human colorectal adenocarcinoma and have been widely used for permeability studies before. To do this we will investigate the role and regulating mechanisms of butyrate to counteract the effects of pro-inflammatory cytokines and oxidative stress factors on the functioning and expression patterns of tryptophan transporters. Likewise, we aim to measure the activity of antioxidant enzymes such as glutathione, catalase and super oxide dismutase of fibroblasts obtained from the different individual groups in response to butyrate.

Publications

Rode J* & Yang L*, König J, Hutchinson AN, Wall R, Venizelos N, Brummer RJ, Rangel I, Vumma R. Butyrate Rescues Oxidative Stress-Induced Transport Deficits of Tryptophan: Potential Implication in Affective or Gut-Brain Axis Disorders. Neuropsychobiology 2020:1-11. doi: 10.1159/000510886. *equal contribution