ACE2 links amino acid malnutrition to microbial ecology and intestinal inflammation

Malnutrition affects up to one billion people in the world and is a major cause of mortality. In many cases, malnutrition is associated with diarrhoea and intestinal inflammation, further contributing to morbidity and death. The mechanisms by which unbalanced dietary nutrients affect intestinal homeostasis are largely unknown. Here we report that deficiency in murine angiotensin I converting enzyme (peptidyl-dipeptidase A) 2 (Ace2), which encodes a key regulatory enzyme of the renin-angiotensin system (RAS), results in highly increased susceptibility to intestinal inflammation induced by epithelial damage. The RAS is known to be involved in acute lung failure, cardiovascular functions and SARS infections. Mechanistically, ACE2 has a RAS-independent function, regulating intestinal amino acid homeostasis, expression of antimicrobial peptides, and the ecology of the gut microbiome. Transplantation of the altered microbiota from Ace2 mutant mice into germ-free wild-type hosts was able to transmit the increased propensity to develop severe colitis. ACE2-dependent changes in epithelial immunity and the gut microbiota can be directly regulated by the dietary amino acid tryptophan. Our results identify ACE2 as a key regulator of dietary amino acid homeostasis, innate immunity, gut microbial ecology, and transmissible susceptibility to colitis. These results provide a molecular explanation for how amino acid malnutrition can cause intestinal inflammation and diarrhoea

Intestinal absorption and vitamin levels: is a new focus needed?

Vitamins are micronutrient chemical compounds that cannot be synthesized by an organism but are essential for human metabolism and life. They act as required intermediaries, cofactors or coenzymes in many of the reactions of normal metabolism. In addition, anti-inflammatory effects have been reported for specific vitamins. In inflammatory bowel disease (IBD), vitamin deficiency is often due to malnutrition (due to a decreased food intake) or malabsorption (due to inflamed, malfunctioning mucosa and diarrhea) which results in anemia. Vitamin B(12) and folic acid supplementation may be necessary in IBD patients, especially those with Crohn's disease (CD) with either inflammation of the terminal ileum or after resection of the terminal ileum. It is also recommended during therapy with sulfasalazine as this compound inhibits the absorption of vitamin B(12). Patients with high or continuous inflammatory CD activity and frequent therapy with steroids have an increased risk of low bone mineral density and vitamin D deficiency. These should be monitored regularly and vitamin D should be supplemented. In a recent trial, a trend towards a reduced risk of relapses in CD patients treated with vitamin D was reported. Only limited studies and case reports exist on other vitamin deficiencies, e.g. vitamins A, B(1), B(2), niacin, B(6), C, E and K, found in IBD patients. These are summarized in this review. Regular nutritional monitoring in IBD patients is warranted and requires the special attention of treating physicians and dieticians