Dietary Nitrogen and Its Role in the Gut Microbiome and Inflammatory Bowel Disease: A Narrative Review

Abstract

In recent years, gut microbiota has emerged as a critical regulator of gastrointestinal health and disease, with its role in inflammatory bowel disease (IBD)-including Crohn's disease and ulcerative colitis-being particularly significant. Among the many factors influencing the gut microbiota, dietary components such as fibers, fats, and polyphenols have received substantial attention. However, nitrogen-containing compounds, such as amino acids, nitrates, urea, and even nucleic acids, such as purines, remain underexplored despite their integral role in shaping microbial ecology, host metabolism, and immune responses. Some of these compounds are metabolized by gut bacteria into bioactive molecules such as short-chain fatty acids, ammonia, and nitric oxide, which exert diverse effects on mucosal integrity and inflammation. IBD pathophysiology is characterized by chronic inflammation, microbial dysbiosis, and compromised epithelial barriers. Nitrogen metabolism contributes significantly to these processes by influencing microbial composition, metabolite production, and host immune pathways. The breakdown of various nitrogen-containing compounds in the body leads to the production of byproducts, such as ammonia and hydrogen sulfide, which have been implicated in mucosal damage and immune dysregulation. At the same time, nitrogen-derived molecules, such as short-chain fatty acids and nitric oxide, exhibit protective effects, underscoring the dual role of dietary nitrogen in health and disease. This narrative review highlights the complex interactions between dietary nitrogen sources, gut microbiota, and IBD pathogenesis. We summarize the mechanisms by which nitrogen compounds influence microbial dynamics, identify their contributions to inflammation and barrier dysfunction, and explore their therapeutic potential. Multidisciplinary approaches integrating clinical, metabolomic, and microbiome research are essential to unravel the full scope of nitrogen's role in gut health and identify novel therapeutic targets.

Keywords: inflammatory bowel disease; nitrogen; protein; purines.

Figure 1

Dietary nitrogen’s effect on gut permeability, mucus layer integrity and immune modulation.

Figure 2

The positive and negative effects of gut microbial-derived metabolites from dietary nitrogen sources on the colon, including their physiological and biochemical impacts. Figure created using Biorender.