Serine protease inhibitors in legume seeds: from antinutrients towards putative gut health maintainers

Legume seeds contain proteins with serine protease inhibitor activity. Serine protease inhibitors (SPI) have traditionally been regarded as antinutritional compounds because of their ability to inhibit digestive serine proteases. Evidence from animal studies has demonstrated pancreatic hypertrophy following consumption of diets containing raw legume seeds and/or purified SPI, although these effects may be biased by factors such as the overall poor protein digestibility of the raw seeds. Accumulating evidence indicates that legume seed-derived SPI have anti-inflammatory activity with potential relevance to gastrointestinal health. However, the mechanisms underlying these effects remain incompletely understood. This review examines current knowledge of legume seed-derived SPI in the context of both their antinutritional properties and their potential role in mitigating gut inflammation. Particular attention is given to proposed mechanisms involving SPI-mediated inhibition of neutrophil elastase, which may in turn reduce matrix metalloprotease activation and downstream inflammatory pathways. Available animal studies further suggest that a proportion of ingested SPI can remain structurally intact and biologically active in the distal intestine. Together, this evidence highlights the dual biological role of SPI and identifies key knowledge gaps, including their intestinal bioavailability and relevance to human gastrointestinal disorders.