Wild guava (Psidium guajava L.) leaf extract: multifaceted effects on gut microbiota, gene expression, and metabolic regulation in a zebrafish model of type 2 diabetes.

Wild guava (Psidium guajava L.) leaf extract shows promise for type 2 diabetes mellitus (T2DM) management through its effects on the gut microbiota, gene expression, and metabolism. This study examined the extract's effects on probiotic growth, gut microbiota, and diabetes-related gene expression in a zebrafish T2DM model. The extract enhanced probiotic growth of Lactobacillus casei, L. plantarum, and YC-381 by up to 33.11% in hyperglycaemic conditions. In diabetic zebrafish, it restored gut microbiota diversity, reduced pathogenic genera, and increased beneficial taxa like Leuconostoc and Bacillus. Functional analysis showed improved microbial polyphenol and lipid metabolism. The extract downregulated ACC1, normalised insulin receptor expression, reduced SGLT1, and moderately increased GLP1. Transcriptomic analysis revealed the homeostatic effects of the extract on metabolic pathways, in contrast to the pharmacological modulation of metformin. These results demonstrate the potential of wild guava leaf extract as a T2DM intervention through its effects on the microbiome-transcriptome-phenotype axis.