Berberine as an Antimicrobial Agent and Gut Microbiota Modulator: Mechanisms and Therapeutic Potential

Berberine exhibits remarkable antimicrobial properties against various pathogens, including bacteria, fungi and viruses. It has long been used to treat gastrointestinal disorders like diarrhea. Importantly, berberine exerts profound effects on the gut microbiota. The mechanisms of action are complex and diverse, including but not limited to modulating microbiota abundance and maintaining microbial homeostasis. Berberine can exert therapeutic effects by promoting intestinal production of short-chain fatty acids to enrich beneficial microbial populations, and it may also delay disease progression by inhibiting pathogenic bacteria. Furthermore, as one of the most relevant targets of berberine, the gut microbiota also regulate inflammation responses, metabolism, and immune regulation, playing a crucial role in human physiological and pathological processes. Notably, a growing number of berberine derivatives and nano-formulations are emerging as important innovative therapeutics and are playing a key role in advancing the development of natural medicines. However, the specific mechanism of action between berberine and microbiome is still unclear. This review discusses the mechanisms of action and therapeutic potential of berberine, its derivatives, and nanoformulations as antibacterial agents and gut microbiota modulators, aiming to provide more robust evidence for the clinical development and pharmaceutical translation of berberine, thereby achieving the goal of better disease treatment.