The intake of plant-based foods has been shown to lead to a reduction in plasma levels of branched-chain amino acids, phenylalanine, and tyrosine, which are amino acids linked to insulin resistance (Neacsu et al., 2022). Hemp is a high protein crop and stands out due to its quality nutritional profile among gluten-free plant species that provide valuable industrial outputs with less impact on the environment (Yano & Fu ,2023 ). After consuming isoproteic meals rich in hemp or meat, certain plasma microbial metabolites were significantly elevated following the hemp meal and linked to lower levels of insulin and ghrelin. It is important to investigate the impact of plant-based foods on altering plasma amino acid profiles and gut hormone levels, given that diets rich in high-protein crops have been shown to be inversely related to the risk of metabolic syndrome and Type 2 Diabetes (T2D) (Neacsu et al., 2022). Several metabolomics studies have explored the relationship between systemic and microbial metabolites and metabolic diseases, underscoring the importance of comprehending their diverse roles in insulin resistance development for identifying novel therapeutic targets against metabolic disorders.

Skeletal muscle, which is considered a central organ in T2D pathology, has an important role in glucose homeostasis in the body. In insulin resistant skeletal muscle, proximal insulin signalling events are impaired and this blocks the insulin-dependent GLUT4 translocation to the plasma membrane. Thus, impaired glucose uptake in skeletal muscle is often considered a primary defect in T2D and is therefore targeted as a therapeutic strategy against insulin resistance (Abdelmoez et al., 2020). In this study we have conducted a scoping review of human studies that investigated protein microbial metabolites and insulin sensitivity. For our scoping review, Pubmed, Scopus, ScienceDirect databases were searched to determine studies examining the effects of protein microbial metabolites on glucose metabolism. From a total 203 articles initially identified, 17 were included in this review. 11 were epidemiological studies, 6 were clinical studies (including dietary intervention studies). The majority of the identified studies (14 articles) report an inverse relationship of indole-3-propionic acid with T2D development and/or its effect on glucose metabolism. Furthermore, the hippuric acid, benzoic acid and phenylalanine were reported to have a beneficial effect on glucose metabolism (fasting glucose, fasting insulin, HOMA-IR, insulin sensitivity) (Neacsu et al. 2022; Koistinen et al. 2024; Vangipurapu et al. 2020). In summary, our scoping review has identified several promising protein microbial metabolites that may affect peripheral tissue insulin sensitivity and could be used as nutritional therapies for T2D.