Amino acid supplements and metabolic health: a potential interplay between intestinal microbiota and systems control

Abstract

Dietary supplementation of essential amino acids (EAAs) has been shown to promote healthspan. EAAs regulate, in fact, glucose and lipid metabolism and energy balance, increase mitochondrial biogenesis, and maintain immune homeostasis. Basic science and epidemiological results indicate that dietary macronutrient composition affects healthspan through multiple and integrated mechanisms, and their effects are closely related to the metabolic status to which they act. In particular, EAA supplementation can trigger different and even opposite effects depending on the catabolic and anabolic states of the organisms. Among others, gut-associated microbial communities (referred to as gut microbiota) emerged as a major regulator of the host metabolism. Diet and host health influence gut microbiota, and composition of gut microbiota, in turn, controls many aspects of host health, including nutrient metabolism, resistance to infection, and immune signals. Altered communication between the innate immune system and the gut microbiota might contribute to complex diseases. Furthermore, gut microbiota and its impact to host health change largely during different life phases such as lactation, weaning, and aging. Here we will review the accumulating body of knowledge on the impact of dietary EAA supplementation on the host metabolic health and healthspan from a holistic perspective. Moreover, we will focus on the current efforts to establish causal relationships among dietary EAAs, gut microbiota, and health during human development.

Keywords: Aging; Branched-chain amino acids; Diabetes; Essential amino acids; Gut microbiota; Healthspan; Microbes; Obesity; Short-chain fatty acids; Supplement.

Fig. 1

A large panel of factors can modulate the effects of specific amino acid supplements on gut microbiota. Gut microbiota owns a characteristic plasticity, and a lot of factors can modulate its composition, including genetic, epigenetic, and environmental factors (e.g., diet regimen and lifestyle), as well as aging, gender, and healthy or pathological conditions. Dietary supplementations with peculiar amino acid mixtures take place in this complex panorama

Fig. 2

Biochemistry of BCAAs. Plasma (brown), cytosolic (light blue) and mitochondrial (gray) compartments are depicted. Concentrations of branched-chain amino acids (BCAAs) in physiological and pathological conditions are reported in the table. BCAAs can both enter the cell from the plasma and be produced by protein breakdown. Intracellular BCAAs are transaminated in mitochondria by branched-chain aminotransferase (BCAT). The resulting branched-chain α-keto acids (BCKAs, especially α-keto acid from leucine) inhibit branched-chain α-keto acid dehydrogenase kinase, resulting in elevation of the active state of the rate limiting enzyme branched-chain α-keto acid dehydrogenase complex (BCKDH). BCAAs can be oxidized to generate ATP. Carbon originating from BCAAs enters the tricarboxylic acid (TCA) cycle as acetyl-CoA for complete disposal as CO₂. Isoleucine and valine provide carbon for anaplerotic conversion of propionyl-CoA to succinyl-CoA. IB-CoA, isobutyryl-coenzyme A; IV-CoA, isovaleryl-coenzyme A; MB-CoA, α-methylbutyryl-coenzyme A; R-CoA, acyl-coenzyme A