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Defences to pathogens such as SarCoV2 in mammals involves interactions between immune functions and metabolic pathways to eradicate infection while preventing hyperinflammation. Amino acid metabolic pathways represent with other antimicrobial agent potential targets for therapeutic strategies. iNOS-mediated production of NO from Arg is involved in the innate inflammatory response to pathogens and NO overproduction can induce hyperinflammation. The two Arg- and Trp-catabolising enzymes Arg1 and IDO1 reduce the hyperinflammation by an immunosuppressive effect via either Arg starvation (for Arg1) or via the immunoregulatory activity of the Trp-derived metabolites Kyn (for IDO1). In response to amino acid abundance mTOR activates the host protein translation and Coronaviruses use this machinery for their own protein synthesis and replication. In contrast GCN2, the sensor of amino acid starvation, activates pathways that restrict inflammation and viral replication. Gln depletion alters the immune response that become more suppressive, by favouring a regulatory T phenotype rather than a Th1 phenotype. Proliferating activated immune cells are highly dependent on Ser, activation and differentiation of T cells need enough Ser and dietary Ser restriction can inhibit their proliferation. Cys is strictly required for T-cell proliferation because they cannot convert Met to Cys. Restricting Met inhibits both viral RNA cap methylation and replication, and the proliferation of infected cells with an increased requirement for Met. Phe catabolism produces antimicrobial metabolites resulting in the inhibition of microbial growth and an immunosuppressive activity towards T lymphocytes., (© 2021. The Author(s).)

Objective: This study was done to investigate whether an intraveinous infusion of 15N-leucine was accurate to differentiate between endogenous and exogenous nitrogen in the human jejunum after meal ingestion., Subjects: Four healthy human volunteers equipped with an upper jejunal tube., Interventions: The jejunal effluents were collected both under fasting conditions and after ingestion of 300g of yoghurt. The nitrogen, amino acid composition and 15N-leucine enrichment were determined in the digesta., Results: During fasting, the jejunal flow rates (mmol/h) of both total nitrogen and amino acids were stable (6.9 +/- 2.7 and 1.88 +/- 0.79, respectively). After yoghurt ingestion, the flow rate of total nitrogen increased to 28.6 +/- 5.8mmol/h at 2h. The 15N-leucine enrichment in plasma reached a plateau at 4.3 mole % excess after one hour and did not vary significantly after meal ingestion. The 15N-leucine enrichment of the endogenous secretion (Ee) in the jejunum was fitted by the equation: Ee = 2.18[1 - 2.05 x exp( - 0.42 x t)]. After yoghurt ingestion, the enrichment in jejunal secretions decreased during the first 80 min. The endogenous nitrogen, calculated from the 15N-enrichment, significantly increased from 20 to 40min after meal ingestion compared to the basal value (P < 0.05). The estimation of the exogenous nitrogen and amino acid yield 300min after yoghurt ingestion indicated that 62 +/- 30% of the exogenous nitrogen and 75 +/- 12% of the amino acids were absorbed in the upper jejunum., Conclusions: The 15N-leucine-dilution method appears to be a convenient method to differentiate between the exogenous and endogenous contributions to nitrogen fluxes in the intestinal digesta of humans. It can be used in association with dietary protein labelling or in substitution when no labelled dietary proteins are available to compare the digestion as well as the absorption of meals at different levels of the intestine.