Diabetic cardiomyopathy from a gut microbiota perspective: research progress and prospects

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  Figure 1. Dietary fiber is metabolized by gut microbiota to produce substances such as butyrate, bile acids, and TMA. TMA is subsequently oxidized to TMAO in the liver, which then enters the systemic circulation. Butyrate binds to GPR43, activating the PI3K/Akt pathway and inhibiting the HIF-1α signaling pathway, thereby reducing apoptosis and attenuating cardiac fibrosis. Butyrate reduces succinate accumulation, suppressing inflammatory signaling pathways such as NF-κB and mitigating inflammatory responses. As an HDAC inhibitor, butyrate reduces lipid accumulation through activation of the MKK3/p38/PRAK pathway. Bile acids can bind to TGR5, leading to increased intracellular cyclic AMP (cAMP) levels. This activates downstream signaling pathways, including protein kinase A (PKA) and AMPK. Consequently, this inhibits pro-inflammatory pathways such as NF-κB and STAT3, alleviating inflammation. Additionally, TGR5 modulates CD36 activity, thereby regulating lipid metabolism. TMAO activates the NLRP3 inflammasome and induces inflammatory responses via NF-κB inflammatory signaling. TMAO also activates the Smad3 pathway, exacerbating cardiac fibrosis, and causes mitochondrial damage.