Lactobacillus acidophilus KLDS1.0901 ameliorates non-alcoholic fatty liver disease by modulating the tryptophan metabolite indole-3-aldehyde and acting on its receptor AhR

KLDS1.0901 on NAFLD symptoms was suppressed after the inhibition of the IAld receptor aromatic hydrocarbon receptor (AhR), suggesting that the bacterium relies on the AhR signaling pathway to mediate its effect on NAFLD. Cellular experiments showed that IAld significantly reduced triglyceride content, decreased lipid accumulation, and increased glycogen levels in oleic acid-induced cells. The effects of IAld on gene transcription levels in oleic acid-induced HepG2 cells were further analyzed using high-throughput sequencing. Transcriptomic analysis revealed that IAld regulates key pathways, including the NF-κB, chemokine and AGE-RAGE signaling pathways. Our study identified the ameliorative effects of tryptophan metabolites, particularly IAld, on NAFLD, along with the underlying mechanisms, offering new insights into potential treatment strategies for NAFLD.