Calcium alginate STB microgels co-administering L-theanine and Blautia coccoides are associated with ameliorate obesity and metabolic syndrome in mice associated via the gut-SCFAs-adipose axis

pH-responsive STB Microgels enable targeted oral delivery of B. coccoides. • Co-encapsulating L-theanine and Blautia synergistically mitigates obesity and steatosis. • STB Microgels remodel gut microbiota and significantly boost SCFAs production. • STB Microgels promotes WAT browning, potentially via the Gut-SCFAs-Adipose axis. With the sharp increase in the global prevalence of obesity and its complications, traditional treatments face significant challenges. Recently, the strategy of co-delivering probiotics and active substances for weight loss has garnered widespread attention. We designed and fabricated calcium alginate-based SA@The/Bla Microgels (STB Microgels) for the co-encapsulation of the next-generation probiotic Blautia coccoides ( B. coccoides ) and the natural compound L-theanine to ameliorate obesity and metabolic syndrome. The optimized microgels had a particle size of 253 μm and a B. coccoides encapsulation efficiency of 83.41% ± 3.37%. They formed a pH-responsive physical matrix that resisted gastric acid degradation through protonation-induced densification and enabled targeted intestinal release via ion-exchange mechanisms. In vivo imaging confirmed that encapsulation significantly prolonged the gastrointestinal retention and persistence of B. coccoides . In a high-fat diet (HFD)-induced obese mouse model, STB Microgels effectively alleviated weight gain, dyslipidemia, and hepatic steatosis. Mechanistically, the treatment remodeled the gut microbiota by enriching beneficial bacteria such as B. coccoides and increasing the production of short-chain fatty acids (SCFAs). These increased SCFAs were consistent with the upregulation of thermogenic genes (e.g., Ucp1 , Prdm16 ) in adipose tissues, indicative of white adipose tissue browning and brown adipose tissue activation. Consequently, this co-encapsulation strategy is associated with the amelioration of metabolic disorders, potentially via the “Gut-SCFAs-Adipose Axis” offering an engineered bio-delivery strategy for oral probiotics. Download: Download high-res image (378KB) Download: Download full-size image