Metabolic Profiling of the Gut-Brain Axis in a Murine Model of Ulcerative Colitis with Raman Spectroscopy

The gut-brain axis (GBA) enables a bidirectional crosstalk between the enteric and central nervous systems and plays a critical role in inflammatory diseases of the gut. This study is the first demonstration of the utility of Raman spectroscopy (RS) in capturing a snapshot of the biochemical changes that modulate the GBA and identify vibrational bands that are evidence of metabolites present in a murine model of ulcerative colitis. Acute colitis was induced in mice by administering dextran sulfate sodium (DSS) in drinking water. RS measurements identified 21 significant peaks in the serum, 21 in the cecum, and 22 in the thalamus region of the brain; these peaks were associated with broad metabolite classes and showed strong correlation to disease activity in colitis mice relative to healthy mice. Our findings showed that the thalamus has the most metabolite changes in the DSS-colitis model rather than the hypothalamus, which is known to be crucial in GBA communication. We identified six biochemical species, including unsaturated fatty acids, lipids, triglycerides, proteins/amide III, tryptophan, and threonine, that were common between the serum, cecum, and thalamus and may serve as early biomarkers of inflammatory response that drive gut-brain communication. Further, a Pearson's correlation analysis highlighted that neurotransmitters in the thalamus had moderate-to-strong correlations to serum amino acids and lipids/fatty acids in the gut. This fundamental study provides a snapshot of the early biochemical changes that enable crosstalk between the gut and brain in ulcerative colitis that can be translated to other disorders of the gut or brain in the future.