A study investigated how total flavonoids from the plant Abelmoschus manihot (TFA) improve diabetic nephropathy in db/db mice through regulation of the gut-kidney axis[2]. Administration of TFA reduced the ratio of albumin to creatinine in urine and significantly changed the composition of the intestinal flora – increasing the amount of Dietzia, Faecium, Streptococcus and Blautia bacteria, while decreasing Bacteroidetes, Firmicutes and other pathogenic species[2]. In serum metabolites, TFA increased levels of quercetin-3-glucuronide and n-cinnamylglycine, but decreased cortisol concentrations[2]. Gene analysis in the kidney revealed that TFA repressed the expression of genes related to neutrophil extracellular trap formation and steroid hormone biosynthesis[2]. In contrast, treatment with irbesartan alone did not significantly affect specific renal pathways in these mice[2]. The results suggest that TFA attenuates the progression of diabetic nephropathy through three mechanisms: modulation of gut flora, regulation of circulating metabolites, and suppression of renal genes[2].