Altered mouse cecal microbiome-serum enterolignans relationships in response to dietary lignans ingested through whole flaxseed or flaxseed hull.

Flaxseed (FS) is rich in bioactive compounds, including fiber and lignans, which provide health benefits largely mediated by gut microbial metabolism. However, gut microbiota responses, including their relationship with fiber- and lignan-derived microbial metabolites (short chain fatty acids (SCFA) and enterolignans enterodiol and enterolactone), remain unclear. We addressed this through administration of an isocaloric flaxseed (FS) or flaxseed hull (FH) diet to female mice, where FH provided a higher amount of fiber and lignan secoisolariciresinol diglucoside compared to FS. Both diets increased cecal SCFA and serum enterolignans concentrations compared to the basal control diet (BD). Compared to FS, FH increased serum secoisolariciresinol, enterodiol, and total lignans, but not SCFA concentrations. FS and FH increased α- and β-diversity and altered microbiota composition and functional potential compared to BD, but no differences were observed between FS and FH, except for altered abundance of select taxa and a limited number of functions. However, the two diets altered the microbial network structure, including keystone species shifts from Intestinimonas in FS to Carnobacterium in FH, and taxa relationships with enterolignans and SCFA. Our findings suggest that while intestinal microbiota composition responses to whole flaxseed result in increased circulating enterolignans and intestinal SCFA production, FH can further elevate serum enterolignans via reorganization of interactions among taxa.