Gut Microbiota-Mediated Degradation of Food-Grade Lambda-Carrageenan by and Its Role in Inflammation.

Concerns about the safety of food additives have intensified among consumers, scientists, and policymakers. Ensuring the safety of these additives is crucial to public health. Carrageenan (CGN), a common additive in the food industry, has become the subject of controversy, particularly regarding whether it can be degraded in the gastrointestinal tract, forming degraded carrageenans (dCGNs) that may pose health risks. This study is among the first to identify C3 as a key gut bacterium involved in the degradation of food-grade lambda-CGN (L-CGN). Using high-performance liquid chromatography (HPLC), thin-layer chromatography (TLC), and metabolic analysis, we confirmed the ability of this bacterium to degrade L-CGN. Importantly, we found that the microbiota-generated dCGNs significantly increased nitric oxide (NO) and COX-2 production and upregulated pro-inflammatory genes, including , , and , in macrophages. This study also highlights how microbial degradation of L-CGN can drive inflammation, particularly through the activation of the Nrf2 and NLRP3 pathways. These results suggest that microbial degradation of L-CGN in the gut may contribute to inflammation, underscoring the need to better understand microbial interactions with food-grade L-CGN, particularly in the context of colon health and inflammation-related diseases such as inflammatory bowel disease.