Tissue-specific effect of colitis on protein synthesis in mice: impact of the dietary protein content

"As previously reported, acute inflammation severely affects colon metabolism by stimulating protein anabolism [4, 9, 18]. Because colon protein content was not modified along the colitis course and resolution despite a higher protein synthesis rate, this increase in biosynthesis might reflect colon repair after epithelium erosion, with possibly a higher epithelial cell loss in the lumen. The locally induced inflammation is known to provoke an increased amino acid need for protein synthesis in the colon, not only when inflammation is maximal (day 7–10) [19], but also likely during the healing process. This increase, notably at a time when dietary daily intake was reduced, could have been compensated by amino acids supplied by other tissues, such as muscle. A reduced protein synthesis in muscle would also spare amino acids for increased protein synthesis in the colon, liver and spleen. Indeed, muscle is a major contributor to restore protein and energy losses in situations where protein catabolism is manifest such as starvation [20], acute injury [21] or chronic inflammation [9]."

"The present study shows that the protein metabolism modifications are modulated by the dietary protein content. The moderately high-protein diet (P30%), which has been recently shown to improve epithelial repair after an acute colitis episode [14], was associated with a lower protein synthesis rate, restoring initial level in colon compared to the two other diets [14% and 55% protein]. It is noteworthy that several colitis induced alterations were restored earlier with P30 diet consumption compared to the two other diets, such as body weight, caecal protein content, spleen and muscle protein synthesis rates. These changes coincided with the recovery of P30-fed mice that showed less inflammation and bacterial translocation (as evidenced by measuring the circulating LPS-BP concentration [14]) and faster colon repair in accordance with an earlier restoration of initial protein synthesis colon as shown in the present study."

"Our finding that the P30 diet restores rapidly and sustainably the initial (before colitis induction) colon protein synthesis can be related to our previous study in which we showed that P30 diet improved (when compared to the P14 diet) the colonic mucosal healing process by accelerating inflammation resolution, increasing epithelial repair, reducing permeability, and inducing epithelial hyperproliferation [14]. This suggests that the P30 diet, by furnishing an increased amount of amino acids, helps in the restoration of the colon epithelium, thus explaining the less active protein synthesis at this site. However, the relative amount of amino acids that is devoted to the restoration of the colonic epithelium remains to be determined when compared to other amino acid-consuming processes involved in inflammation. We previously showed that a specific mixture of amino acids given to rats after colitis induction was able to improve the colon regeneration/re-epithelialization, and this amelioration was found to coincide with a reduction of the stimulated protein synthesis rate in the colon when compared to control animals not receiving the amino acid mixture [23]. In sharp contrast, by further increasing the protein content in the diet (P53), we did not observe in this study any effect on the colon protein synthesis rate when compared to the P14 diet. This result can be ascribed to the deleterious effects of the P53 diet on the disease activity index, both in intensity and duration after a DSS challenge [14]. The reasons that would explain how a very high-protein diet consumption, although furnishing more amino acids is counterproductive after colitis induction, are not clear. One possibility is that by increasing the protein content in the diet, a larger amount of the dietary and endogenous protein escapes digestion in the small intestine, and thus reaches the large intestine. As a consequence, the microbiota produces an increased amount of amino acid-derived metabolites, some of which (hydrogen sulphide, ammonium, p-cresol) being known to be deleterious for the colonic epithelial cells, notably in terms of energy metabolism [24]."

"In conclusion, our study highlights the severe impact of acute colonic inflammation not only on the metabolism of proteins in the splanchnic area, but also in the peripheral tissues. The ability of the P30 diet to restore a normal protein synthesis in the colon may correspond to its documented beneficial effect on mucosal healing. In addition, the recovery of the initial protein synthesis rate in the various tissues in the period of time following colitis induction appears to be modulated by the amount of protein in the diet, with the P30 diet being more effective than the P53 diet."