Gut Microbiota as the Link between Elevated BCAA Serum Levels and Insulin Resistance

Abstract

The microbiota-harboring human gut is an exquisitely active ecosystem that has evolved in a constant symbiosis with the human host. It produces numerous compounds depending on its metabolic capacity and substrates availability. Diet is the major source of the substrates that are metabolized to end-products, further serving as signal molecules in the microbiota-host cross-talk. Among these signal molecules, branched-chain amino acids (BCAAs) has gained significant scientific attention. BCAAs are abundant in animal-based dietary sources; they are both produced and degraded by gut microbiota and the host circulating levels are associated with the risk of type 2 diabetes. This review aims to summarize the current knowledge on the complex relationship between gut microbiota and its functional capacity to handle BCAAs as well as the host BCAA metabolism in insulin resistance development. Targeting gut microbiota BCAA metabolism with a dietary modulation could represent a promising approach in the prevention and treatment of insulin resistance related states, such as obesity and diabetes.

Patients with low muscle mass have characteristic microbiome with low potential for amino acid synthesis in chronic liver disease

“…Although it is controversial whether BCAAs contribute significantly to the systemic BCAA pool, several reports have shown an association between blood BCAA concentrations and the microbiome 4 . Pedersen et al 24 reported that the number of genes associated with BCAA synthesis encoded in bacteria correlated with the concentration of BCAAs in the blood and affected insulin resistance.…”

“…The association are also affected by various factors, including butyrate and LPS, which may be anti-inflammatory and pro-anabolic mediators 2 , 3 . It has also been suggested that the amino acids synthesized by the microbiome are associated with sarcopenia 4 . The patients with chronic liver disease are at risk of ammoniaemia, and the risk is reduced by antibiotics and laxatives.…”

“…compared the microbiome in cirrhotic patients with or without sarcopenia and found low levels of several categories of genes, including enzymes related to BCAA synthesis. Recently, it has become clear that the microbiome is associated with serum BCAAs 4 , and there is a need for more detailed evaluation in clinical practice. We examine fecal samples to characterize the proportions and roles of microbiome in patients classified into the normal skeletal muscle mass index (N-SMI) group and low SMI (L-SMI) group.…”

Pectin with various degrees of esterification differentially alters gut microbiota and metabolome of healthy adults

“…Myo‐inositol, which was the unique intracellular metabolite identified from the microbiota after treatment with low‐esterified pectin L13, could act as a nutraceutical antioxidant and protect the kidney against injuries due to cadmium‐induced toxicity (Pallio et al, 2019). Leucine, which is a kind of branched amino acid associated with the development of obesity and insulin resistance, increased on pectin L102 supplementation (Gojda & Cahova, 2021; Zhang et al, 2020).…”

Lactiplantibacillusplantarum ATG-K2 Exerts an Anti-Obesity Effect in High-Fat Diet-Induced Obese Mice by Modulating the Gut Microbiome

“…Their production shares the same multienzyme pathway; however, there is a difference in substrate initiation of the pathway. In addition, a side-product such as H 2 is utilized by other species in cross-feeding to avoid the accumulation of H 2, which would inhibit the ability of primary fermenters [ 33 , 34 ]. It suggests that the gut microbiome contributes enzymes with cross-feeding, and the beneficial effect of the gut microbiome is favorable to SCFA and BSCFA production.…”