Abstract
There is great interest in safe and effective alternative therapies that could benefit patients with inflammatory bowel diseases (IBD). L-arginine (Arg) is a semi-essential amino acid with a variety of physiological effects. In this context, our aim was to investigate the role of dietary Arg in experimental colitis. We used two models of colitis in C57BL/6 mice, the dextran sulfate sodium (DSS) model of injury and repair, and Citrobacter rodentium infection. Animals were given diets containing (1) no Arg (Arg0), 6.4 g/kg (ArgNL), or 24.6 g/kg Arg (ArgHIGH); or (2) the amino acids downstream of Arg: 28 g/kg L-ornithine (OrnHIGH) or 72 g/kg L-proline (ProHIGH). Mice with DSS colitis receiving the ArgHIGH diet had increased levels of Arg, Orn, and Pro in the colon and improved body weight loss, colon length shortening, and histological injury compared to ArgNL and Arg0 diets. Histology was improved in the ArgNL vs. Arg0 group. OrnHIGH or ProHIGH diets did not provide protection. Reduction in colitis with ArgHIGH diet also occurred in C. rodentium-infected mice. Diversity of the intestinal microbiota was significantly enhanced in mice on the ArgHIGH diet compared to the ArgNL or Arg0 diets, with increased abundance of Bacteroidetes and decreased Verrucomicrobia. In conclusion, dietary supplementation of Arg is protective in colitis models. This may occur by restoring overall microbial diversity and Bacteroidetes prevalence. Our data provide a rationale for Arg as an adjunctive therapy in IBD.
Highlights
Inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn’s disease (CD), remains a major public health problem (Torres et al, 2017; Ungaro et al, 2017)
The shortening of the colon, which is an indicator of disease severity in dextran sulfate sodium (DSS)-treated mice (Singh et al, 2018), was improved in mice on the ArgNL or ArgHIGH diet compared to those fed the Arg0 diet, and was improved on the ArgHIGH diet when compared to the ArgNL diet (Figure 1B)
Since we found that Orn and Pro concentrations were increased in the serum and/or colon of DSS-treated mice fed the ArgHIGH diet, we reasoned that Arg might exert its protective effect in DSS colitis through the synthesis of these two amino acids
Summary
Inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn’s disease (CD), remains a major public health problem (Torres et al, 2017; Ungaro et al, 2017). The etiology of IBD is undoubtedly multifactorial and is thought to result from the complex interplay between genetic susceptibility (Liu and Stappenbeck, 2016), the gut microbiota (Frank et al, 2007), and environmental factors (Kaser et al, 2010), resulting in a dysregulated mucosal immune response. In this context, biologic therapies for IBD, which include anti-TNFs (Sandborn et al, 2012), anti-IL-12/23p40 (Mannon et al, 2004), anti-integrins (Engel et al, 2018), and others have been deployed to limit the chronic colonic inflammation. Alternative therapies that would be safe, well-tolerated, cost-effective, and rationally-based that could beneficially impact IBD patients would be ideal
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call