Arginine metabolism regulates the pathogenesis of inflammatory bowel disease

Abstract

The pathogenesis of inflammatory bowel disease (IBD) is related to genetic susceptibility, enteric dysbiosis, and uncontrolled, chronic inflammatory responses that lead to colonic tissue damage and impaired intestinal absorption. As a consequence, patients with IBD are prone to nutrition deficits after each episode of disease resurgence. Nutritional supplementation, especially for protein components, is often implemented during the remission phase of IBD. Notably, ingested nutrients could affect the progression of IBD and the prognostic outcome of patients; therefore, they should be cautiously evaluated prior to being used for IBD intervention. Arginine (Arg) is a semi-essential amino acid required for protein synthesis and intimately associated with gut pathophysiology. To help optimize arginine-based nutritional intervention strategies, the present work summarizes that during the process of IBD, patients manifest colonic Arg deficiency and the turbulence of Arg metabolic pathways. The roles of Arg–nitric oxide (catalyzed by inducible nitric oxide synthase) and Arg–urea (catalyzed by arginases) pathways in IBD are debatable; the Arg–polyamine and Arg–creatine pathways are mainly protective. Overall, supplementation with Arg is a promising therapeutic strategy for IBD; however, the dosage of Arg may need to be carefully tailored for different individuals at different disease stages. Additionally, the combination of Arg supplementation with inhibitors of Arg metabolic pathways as well as other treatment options is worthy of further exploration.

On-Demand Dissociable Antibacterial Self-Healing Hydrogel with Rapid Arginine-Related Biosynthesis Capacity to Promote Full-Thickness Bacteria-Infected Wound Healing

“…In the other ion modes, the KEGG analysis for metabolites with significantly different intensities did not yield any pathways with the significant threshold of P < 0.05 as the relatively small number of metabolites. The arginine and related pathways have been mentioned frequently in recent studies, suggesting that arginine supplementation would enhance wound healing. , d -ornithine, 4-acetamidobutanoic acid, and creatine are all important metabolites within the arginine metabolism pathway . Arginine is the precursor of creatine and 4-acetamidobutanoic acid and could be hydrolyzed by arginase to ornithine and urea .…”

“…39,40 D-ornithine, 4-acetamidobutanoic acid, and creatine are all important metabolites within the arginine metabolism pathway. 41 Arginine is the precursor of creatine and 4acetamidobutanoic acid and could be hydrolyzed by arginase to ornithine and urea. 42 Thus, with the downregulated ornithine and upregulated creatine and 4-acetamidobutanoic acid, we could speculate that the arginine content could be elevated, thus accelerating wound closure.…”

Altered endocannabinoidome bioactive lipid levels accompany reduced DNBS-induced colonic inflammation in germ-free mice

“…Ly6g , a neutrophil-expressed maturation marker [ 38 , 39 ] was significantly increased by DNBS in CR mice, but only showed trends towards increases in ABX and GF mice (Fig. 3 H), while the activated neutrophil marker Arginase ( Arg1 ), the release of which is associated with T-cell dysfunction (which is implicated in the development of inflammation in IBD [ 40 , 41 ], was massively upregulated in CR and ABX mice in response to DNBS (though only significantly in the latter), with relatively no effect in GF mice (Fig. 3 I).…”

Dietary Habits and Nutrient Deficiencies in a Cohort of European Crohn’s Disease Adult Patients

“…Our results stress the importance of specific amino acid supplementation, necessary in IBD patients with active disease. For example, the deficiency of arginine has been linked to gut pathophysiology in IBD patients [ 30 ]. The results of this study also suggest the need for nutrient and micronutrient supplementation in CD patients: vitamins (A, C, E, B6 and folates), minerals (iron, potassium, calcium, phosphorus, magnesium, copper and iodine) and also fatty acids (especially short- and medium-chain fatty acids and also DHA).…”