Neurobiologist Fievos Christofi, PhD, AGAF, and his team of researchers are shedding light on the ‘little brain’ of the gut, or
enteric nervous system (ENS), to better understand the neurological components of gut motility, secretions and gastrointestinal
The ENS contains more neurons than the spinal cord and is capable of functioning autonomously to coordinate gut motor
reflexes and visceral sensation of the gut. Dysregulation of these activities and gut-to-brain communication contribute to GI
symptoms and visceral pain in motility disorders, irritable bowel syndrome (IBS) or inflammatory bowel diseases (IBD). These
disorders carry heavy economic burdens and impact quality of life, and current treatment protocols are inadequate. More
effective treatments are needed and purines are showing great promise as providing therapeutic potential for IBS and IBD.
For more than 20 years, Dr. Christofi has been researching the role that purines (e.g., adenosine, ATP, UTP) play in the health
and disease of the gut. Translational studies have become his priority to provide the most benefit to patients who suffer from
GI disorders or IBD through therapeutic strategies. A key is to understand mechanisms of abnormal purinergic signaling at
all levels of gut reflexes and the ‘human little brain.’
Sensory targets of investigation with therapeutic
potential are purinergic receptors and enzymes in
enterochromaffin cells, intrinsic sensory neurons and
enteric glia. A new initiative with collaborators at
the National Institute of Diabetes and Digestive and
Kidney Diseases is to test pipeline purinergic drugs
in pre-clinical models of IBD and IBS. NIH studies are
also determining if gene expression profiles can be
used as biomarkers of disease, disease severity, to
distinguish between types of IBD (UC and CD) and in
the early clinical diagnosis of IBS.
Convincing the scientific community that purinergic
pathways hold potential for the treatment of gut disorders and developing in vitro optical imaging techniques to study the
human gut has been challenging. But the perseverance that Dr. Christofi and his research team have shown will undoubtedly
benefit countless individuals who suffer from GI disorders and IBD.
Neurological Components of
Time-lapse LSM Fluo- 4 (Ca2+) imaging of an intact ganglion in human ‘little
brain.’ Synaptic transmission to fiber tract electrical stimulation (FTS) is
enhanced by adenosine deaminase, suggesting endogenous adenosine is
an inhibitory neuromodulator (arrows, enhanced neural activity).