Legume Intake and Glycemic Control in Individuals With or at Risk of Metabolic Syndrome: Multi‐Omics Insights From Both Observational and Interventional Evidence

To elucidate the legume-specific effects on glycemic control, and the potential mechanisms involving gut microbial co-abundance networks, and short-chain fatty acid (SCFA) metabolism in adults with or at risk of metabolic syndrome (MetS). We analyzed 258 MetS-susceptible adults cross-sectionally and 82 participants in a dietary intervention incorporating black beans. Food frequency questionnaires, glycemic measurements (fasting plasma glucose [FPG], insulin [INS], and homeostatic model assessment for insulin resistance [HOMA-IR]), and multi-omics data (16S rRNA gene sequencing, metabolomics, and SCFA-related genotyping) were integrated. Cross-sectionally, higher mung bean and edamame intakes are consistently associated with lower FPG, while ormosia, black bean, and soybean associated with lower INS and HOMA-IR. In the intervention, black bean consumption decreased FPG (P = 0.018) alongside enrichment of beneficial microbes and a relative suppression of pro-inflammatory taxa. Co-abundance analysis revealed two competing microbial guilds: a butyrate-producing guild positively associated with legumes and inversely with glycemic indices, and a pro-inflammatory guild showing opposite patterns. Furthermore, the rs12994030 variant in a butyrate-synthesis pathway modified the associations of legume intake with INS and HOMA-IR (P for interaction < 0.05). In conclusion, specific legumes confer glycemic benefits in MetS-prone adults, driven by cooperative gut microbial guilds and modulated by butyrate-associated host genetics.