Histidine is an essential amino acid (EAA) in mammals, fish, and poultry. We aim to give an overview of the metabolism and physiological effects of histidine in humans and different animal species through a systematic review following the guidelines of PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). In humans, dietary histidine may be associated with factors that improve metabolic syndrome and has an effect on ion absorption. In rats, histidine supplementation increases food intake. It also provides neuroprotection at an early stage and could protect against epileptic seizures. In chickens, histidine is particularly important as a limiting factor for carnosine synthesis, which has strong anti-oxidant effects. In fish, dietary histidine may be one of the most important factors in preventing cataracts. In ruminants, histidine is a limiting factor for milk protein synthesis and could be the first limiting AA for growth. In excess, histidine supplementation can be responsible for eating and memory disorders in humans and can induce growth retardation and metabolic dysfunction in most species. To conclude, the requirements for histidine, like for other EAA, have been derived from growth and AA composition in tissues and also have specific metabolic roles depending on species and dietary levels.

Weaning transition is often associated with the occurrence of the post-weaning diarrhoea syndrome (PWDS). The reduction of dietary crude protein (CP) has been intensively used as a strategy for controlling PWDS. The aim of the present meta-analysis was to report the effect of the reduction of dietary CP on the intestinal parameters related to the gut health, growth and diarrhoea of post-weaning piglets. A literature review of the articles published from 2006 to 2019 produced 48 articles and, of these 26 were selected. Parameters (bacterial metabolites, pH, microbiota diversity, intestinal morphology, inflammation markers, growth, faecal score) were extracted, expressed as a percentage of the control diet and analysed using a general linear model which included the study, reduction in points of dietary CP, and the ratio of digestible Lysine and dietary CP (dLys/CP) as factors. The reduction of dietary CP decreased ammonia (p < .0001), pH (p = .039), total short-chain fatty acids (SCFAs) (p = .027), biogenic amines including cadaverine (p = .034) and putrescine (p = .030) and the expression of TLR4 (p < .0001) in the intestine and also reduced the faecal score (p = .002). The dLys/CP ratio increased the level of Lactobacilli and the expression of TLR4 (p < .05), and tended to increase acetic acid (p < .1). Crypt depth, villus height, microbiota diversity and growth remained unchanged. In conclusion, this study confirmed that a reduction of dietary CP could reduce bacterial protein fermentation and the production of potentially toxic metabolites. In turn, this could result in lower intestinal inflammation and a decreased risk of diarrhoea in weaning piglets. Graphical Abstract

In order to investigate the effect of a dietary amino acid mixture supplementation in lipopolysaccharide (LPS)-challenged weaned piglets, twenty-seven 28-day-old (8.2 ± 1.0 kg) newly weaned piglets were randomly allocated to one of three experimental treatments for five weeks. Diet 1: a CTRL treatment. Diet 2: an LPS treatment, where piglets were intraperitoneally administered LPS (25 μg/kg) on day 7. Diet 3: an LPS+MIX treatment, where piglets were intraperitoneally administered LPS on day 7 and fed a diet supplemented with a mixture of 0.3% of arginine, branched-chain amino acids (leucine, valine, and isoleucine), and cystine (MIX). Blood samples were drawn on day 10 and day 35, and serum was analysed for selected chemical parameters and proteomics. The LPS and LPS+MIX groups exhibited an increase in haptoglobin concentrations on day 10. The LPS group showed an increased cortisol concentration, while this concentration was reduced in the LPS+MIX group compared to the control group. Similarly, the LPS+MIX group showed a decreased haptoglobin concentration on day 35 compared to the two other groups. Immunoglobulin concentrations were affected by treatments. Indeed, on day 10, the concentrations of IgG and IgM were decreased by the LPS challenge, as illustrated by the lower concentrations of these two immunoglobulins in the LPS group compared to the control group. In addition, the supplementation with the amino acid mixture in the LPS+MIX further decreased IgG and increased IgM concentrations compared to the LPS group. Although a proteomics approach did not reveal important alterations in the protein profile in response to treatments, LPS-challenged piglets had an increase in proteins linked to the immune response, when compared to piglets supplemented with the amino acid mixture. Overall, data indicate that LPS-challenged piglets supplemented with this amino acid mixture are more protected against the detrimental effects of LPS.

General control nonderepressible 2 (GCN2) is a kinase that detects amino acid deficiency and is involved in the control of protein synthesis and energy metabolism. However, the role of hepatic GCN2 in the metabolic adaptations in response to the modulation of dietary protein has been seldom studied. Wild-type (WT) and liver GCN2-deficient (KO) mice were fed either a normo-protein diet, a low-protein diet, or a high-protein diet for 3 wk. During this period, body weight, food intake, and metabolic parameters were followed. In mice fed normo- and high-protein diets, GCN2 pathway in the liver is not activated in WT mice, leading to a similar metabolic profile with the one of KO mice. On the contrary, a low-protein diet activates GCN2 in WT mice, inducing FGF21 secretion. In turn, FGF21 maintains a high level of lipid oxidation, leading to a different postprandial oxidation profile compared with KO mice. Hepatic GCN2 controls FGF21 secretion under a low-protein diet and modulates a whole body postprandial oxidation profile.

Phosphorus (P) is an essential mineral in poultry nutrition, but its low bioavailability from conventional feed ingredients presents a significant challenge for efficient utilization. This study investigated the effects of different P sources (monocalcium phosphate (MCP) and calcium humophosphate (CHP)) and three phytase concentrations (0, 1000, or 2000 FTU/kg of feed) on broiler performance and ileal nutrient digestibility. A total of 600 Cobb 500 male broilers were fed one of six different dietary treatments with 10 replicates per treatment from 11 to 21 d of age. The birds and feed were weighed at 1, 10, and 21 d of age to determine growth performance. At 21 d of age, ileal digesta was collected from all the birds to determine dry matter, organic matter, Ca, P, and ash digestibility. The results indicated that phytase supplementation at 1000 and 2000 FTU/kg improved the feed conversion ratio and P digestibility compared with the non-supplemented group. The broilers fed CHP showed superior P digestibility compared to those fed MCP, regardless of phytase concentration. The results also indicated interactive effects between P source and phytase concentration on the digestibility of dry matter, organic matter, and ash. The findings suggest that CHP enhances nutrient digestibility and could optimize P utilization in broiler diets with phytase inclusion. This report reveals a better understanding of the effects of P sources and phytase concentration on feed digestibility. Further studies are needed to confirm these findings and support improvements in broiler performance under commercial production conditions.