Modulatory Effect of Nicotinic Acid on the Metabolism of Caco-2 Cells Exposed to IL-1β and LPS

Abstract

Inflammatory bowel diseases (IBD) are the most common gastrointestinal inflammatory pathologies. Previous work evidenced a lower content of nicotinic acid (NA) in feces of IBD patients compared to healthy subjects. In the present study, we aimed to understand the effects of NA on intestinal inflammation, as several studies reported its possible beneficial effect, and investigate its influence on inflammation-driven metabolism. NA was tested on a Caco-2 in-vitro model in which inflammation was induced with interleukin-1β (IL-1β) and lipopolysaccharide (LPS), two mayor proinflammatory compounds produced in IBD, that stimulate the production of cytokines, such as interleukin 8. A metabolomics approach, with gas chromatography–mass spectrometry (GC-MS) and nuclear proton magnetic resonance (1H-NMR), was applied to study the metabolic changes. The results showed that NA significantly reduced the level of IL-8 produced in both LPS and IL-1β stimulated cells, confirming the anti-inflammatory effect of NA also on intestinal inflammation. Moreover, it was demonstrated that NA treatment had a restoring effect on several metabolites whose levels were modified by treatments with IL-1β or LPS. This study points out a possible use of NA as anti-inflammatory compound and might be considered as a promising starting point in understanding the beneficial effect of NA in IBD.

Bacillus Subtilis 29784 as a Feed Additive for Broilers Shifts the Intestinal Microbial Composition and Supports the Production of Hypoxanthine and Nicotinic Acid

“…In addition to the abovementioned effects on the microbiome, beneficial effects on intestinal health for both hypoxanthine and nicotinic acid were previously reported. Reduced faecal levels of hypoxanthine or nicotinic acid have both been linked with IBD [ 45 , 49 , 50 ]. Furthermore, both metabolites are able to ameliorate experimental colitis [ 51 , 52 ].…”

B Vitamins and Their Roles in Gut Health

“…It controls inflammation by inhibiting vascular permeability in intestinal tissues by activating the PGD2/DP1 signal in endothelial cells [53]. It also modulated the inflammatory response by enhancing the rate of ATP generation in Caco-2 cells [54]. Interestingly, vitamin B3 engages in various metabolic reactions that alter the cellular redox state and rapamycin signalling pathway [51], thus suppressing the colon's inflammations [53].…”

“…In another in vitro study, cellular metabolites such as glutamine, isoleucine, ornithine, and glycerophosphocholine were downregulated, and glutamic acid was upregulated in inflamed Caco-2 cells. The impairments in the metabolite profile were ameliorated with the addition of vitamin B3 [54], which means that the therapeutic properties of vitamin B3 might be related to improving specific cellular metabolites that were impaired during acute inflammations.…”

Metabolic Alteration in Plasma and Biopsies From Patients With IBD

“…The technical details have already been described in previous articles. 14 Metabolites were identified by using the standard National Institute of Standards and Technology and Golm Metabolome Database mass spectra libraries and by comparison with external standard. Peak detection and deconvolution, filtering, and normalization were performed using a pipeline on Knime.…”