REVIEW ARTICLE Mucosal Healing in Inflammatory Bowel Diseases: Is There a Place for Nutritional Supplementation? Annaïg Lan, PhD,* Franc ¸ois Blachier, PhD,* Robert Benamouzig, MD, PhD, † Martin Beaumont, MS,* Christophe Barrat, MD, ‡ Desire Coelho, PhD, § Antonio Lancha, Jr, PhD, § Xiangfeng Kong, PhD, k Yulong Yin, PhD, k Jean-Claude Marie, PhD, ¶ and Daniel Tomé, PhD* Abstract: Advanced mucosal healing (MH) after intestinal mucosal inflammation coincides with sustained clinical remission and reduced rates of hospitalization and surgical resection, explaining why MH is increasingly considered as a full therapeutic goal and as an endpoint for clinical trials. Intestinal MH is a complex phenomenon viewed as a succession of steps necessary to restore tissue structure and function. These steps include epithelial cell migration and proliferation, cell differentiation, restoration of epithelial barrier functions, and modulation of cell apoptosis. Few clinical studies have evaluated the needs for specific macronutrients and micronutrients and their effects on intestinal MH, most data having been obtained from animal and cell studies. These data suggest that supplementation with specific amino acids including arginine, glutamine, glutamate, threonine, methionine, serine, proline, and the amino acid-derived compounds, polyamines can favorably influence MH. Short-chain fatty acids, which are produced by the microbiota from undigested polysaccharides and protein-derived amino acids, also exert beneficial effects on the process of intestinal MH in experimental models. Regarding supplementation with lipids, although the effects of v-3 and v-6 fatty acids remain controversial, endogenous prostaglandin synthesis seems to be necessary for MH. Finally, among micronutrients, several vitamin and mineral deficiencies with different frequencies have been observed in patients with inflammatory bowel diseases and supplementation with some of them (vitamin A, vitamin D3, vitamin C, and zinc) are presumed to favor MH. Future work, including clinical studies, should evaluate the efficiency of supplementation with combination of dietary compounds as adjuvant nutritional intervention for MH of the inflamed intestinal mucosa. (Inflamm Bowel Dis 2014;0:1–10) Key Words: intestinal mucosal healing, inflammatory bowel diseases, nutritional supplementation I nflammatory bowel diseases (IBD) are characterized by alter- ations of the intestinal mucosa associated with exacerbated immune functions of still unclear etiology. 1 IBD, which include ulcerative colitis (UC) and Crohn’s disease (CD), are both char- acterized by chronic inflammation of the mucosa with alternating relapse and remission episodes. In CD remission, the inflamed mucosa has the possibility to heal progressively, leading to the total disappearance of all mucosal ulcerations; although in clinical practice, this endpoint is difficult to achieve 2 (Fig. 1). For patients with UC, mucosal healing (MH) is described as the absence of friability, blood, erosions, and ulcers in all visualized segments of the gut mucosa. 3,4 According to recent evidence, it seems that an advanced MH coincides with a sustained clinical remission and improved clinical outcomes, as well as reduced rates of hospital- ization and surgical resection. This explains why MH can be considered as a full therapeutic goal and an endpoint for clinical trials for both CD and UC, 5–9 even if MH by itself obviously is not sufficient to cure IBD. 10 Regarding CD more specifically, a recent consensus report by experts concluded that MH is both a relevant and achievable goal, as well as a predictive parameter for the long-term disease course. 7 Although reports on the pharmacological treatment of IBD are numerous, there is still a paucity of information regarding the possible role of alimentary compounds and nutritional supple- ments, which would improve MH in IBD. Indeed, most studies have been related to the effects of dietary compounds on the process of mucosal inflammation itself, this topic being the subject of several review articles. 11–13 The objective of this review is thus to focus on the beneficial effects of dietary supplementation with compounds presumably efficient for intestinal MH improvement. We present the process of MH in IBD with a brief description of the mechanisms involved, and then we examine the dietary com- pounds that seem beneficial in this process. For this purpose, we present and synthesize data obtained from experiments with Received for publication June 16, 2014; Accepted July 3, 2014. From the *UMR 914 INRA/AgroParisTech, Nutrition Physiology and Ingestive Behavior, Paris, France; † Department of Gastroenterology, Avicenne Hospital, Assis- tance Publique-Hôpitaux de Paris, Bobigny, France; ‡ Department of Digestive Sur- gery, Jean Verdier Hospital, Assistance Publique-Hôpitaux de Paris, Bobigny, France; § Laboratory of Applied Nutrition and Metabolism, School of Physical Edu- cation and Sports, University of Sao Paulo, Sao Paulo, Brazil; k Institute of Sub- tropical Agriculture, Chinese Academy of Sciences, Changsha, China; ¶ INSERM U773, Biomedical Research Center Bichat Beaujon/Paris7 University, Paris, France. The authors have no conflicts of interest to disclose. Reprints: Annaïg Lan, PhD, UMR 914 INRA/AgroParisTech, Nutrition Physiol- ogy and Ingestive Behavior, 16, rue Claude Bernard, F-75005, Paris, France (e-mail: annaig.lan@agroparistech.fr). Copyright © 2014 Crohn’s & Colitis Foundation of America, Inc. DOI 10.1097/MIB.0000000000000177 Published online. Inflamm Bowel Dis  Volume 0, Number 0, Month 2014 www.ibdjournal.org | 1 Copyright © 2014 Crohn’s & Colitis Foundation of America, Inc. Unauthorized reproduction of this article is prohibited.