Blueberry anthocyanin-pretreated Akkermansia muciniphila enhances probiotic efficacy against metabolic syndrome via gut microbiota remodeling and hepatic signaling modulation

Abstract

Targeting the gut microbiota is a promising strategy for treating metabolic syndrome (MetS). Previous studies have shown that dietary components, including polyphenols and dietary fibers, can modulate the abundance of Akkermansia muciniphila (AKK). However, whether dietary compounds can enhance the probiotic function of AKK through a pretreatment strategy remains largely unexplored. Here, we revealed a bidirectional interaction between blueberry anthocyanins (BA) and AKK, and demonstrated that BA-pretreated AKK (AA) acts as an enhanced probiotic with superior benefits against MetS. In vitro co-culture experiments demonstrated that BA significantly promoted AKK proliferation, induced distinct morphological changes, and altered the gene expression profile of AKK. Additionally, AKK was capable of rapidly metabolizing anthocyanins. In vivo animal experiments confirmed that both AKK and AA significantly alleviated high-fat diet-induced MetS, with AA outperforming AKK in improving glucose homeostasis, oxidative stress, and systemic inflammation. Mechanistically, transcriptomic and western blot analyses revealed that AA significantly downregulated key hepatic signaling pathways involved in inflammation (JAK2/STAT3). Furthermore, 16S rRNA sequencing results revealed that AA reshaped the gut microbiota in a manner distinct from AKK, specifically enriching Akkermansia and Lachnospiraceae_UCG 006. In conclusion, this study demonstrated that BA pretreatment potentiated the probiotic efficacy of AKK to a certain extent, generating a synergistic “diet-microbe symbiont” and providing a novel dietary approach to alleviate metabolic syndrome through targeted modulation of the gut microbiota.