Bile salts govern protein bioaccessibility and nanostructural assembly during digestion of Nori seaweed

Seaweeds are increasingly recognized as sustainable and nutritious candidates to support future food systems, yet the mechanisms governing their digestibility remain poorly understood. In this work, we show that the cell walls of Nori seaweed ( Porphyra umbilicalis ) are highly resistant to gastric digestion, with protein release occurring primarily during the intestinal phase. Using a multiscale analytical approach including advanced tools such as small-angle X-ray and neutron scattering and nanotomography, we tracked in vitro digestion-induced nanoscale structural reorganization. We found that porphyran-rich extracellular networks restrict enzyme accessibility during gastric digestion, whereas bile salts in the intestinal environment promote polysaccharide and protein solubilization, enhancing proteolysis. These interactions, in turn, hinder the structural ordering and correlation of bile salts nanomicelles in the digesta. These findings reveal the key role of bile salts in the digestion process, not only governing protein digestibility, but also influencing the nanostructuring of digestion products. More broadly, this work establishes a mechanistic framework to investigate how nanoscale self-assembly during digestion influences nutrient transport and physiological responses.