Solubilized lignin promotes the growth of Akkermansia muciniphila and improves insulin sensitivity.

Solubilized lignin (SL) is a water-soluble derivative of lignin, which is typically classified as an insoluble dietary fiber and is predicted to possess structural and physicochemical properties that are distinct from those of conventional dietary fibers. In this study, we evaluated the effects of SL intake on gut microbial composition, intestinal barrier function, and insulin sensitivity in mice. SL supplementation significantly increased the abundance of Akkermansia muciniphila in both lean and diet-induced obese (DIO) mice. In vitro, SL supported the growth of A. muciniphila, suggesting a unique substrate-utilization mechanism. In DIO mice, SL intake improved insulin sensitivity, as evidenced by reduced blood glucose levels during insulin tolerance tests. Mechanistically, SL-induced increases in A. muciniphila were accompanied by modest improvements in intestinal barrier function and reduced expression of intestinal inflammatory markers, which may be associated with improved insulin sensitivity. In addition, predicted microbial pathway analysis indicated that SL-induced alterations in fecal carbohydrate metabolism may also be linked to improved glucose homeostasis. Collectively, these findings indicate that SL acts as a prebiotic for A. muciniphila and may ameliorate insulin sensitivity through the microbiota-mediated modulation of gut barrier integrity and metabolic function. Thus, SL intake may represent a novel dietary strategy for targeting specific gut microbes and mitigating metabolic disorders.