Antibiotic cocktails (ABX) serve as potent therapeutic interventions for refractory ulcerative colitis (UC), yet invariably induce gut dysbiosis. This study demonstrates that pectin oligosaccharides synergistically enhance ABX efficacy by restoring gut microbiota balance and selectively enriched antibiotic-resistant Parabacteroides goldsteinii in a colitis mouse model. Our results further indicate that the gavage administration of P. goldsteinii AM58-2XD markedly alleviated colitis via enhancing the branched-chain amino acid metabolic pathway, particularly by facilitating valine metabolism. Notably, these anticolitis effects were partially attenuated in P. goldsteinii ΔilvE mutants, which are defective in valine-derived isobutyrate (IBN) biosynthesis. We further demonstrated that exogenous IBN supplementation effectively alleviated colitis symptoms in mice and enhanced gut barrier function via activation of the peroxisome proliferator-activated receptor γ (PPARγ) pathway. Conditional knockout of PPARγ in Caco-2 intestinal epithelial cells markedly abrogated the IBN-induced enhancement of tight junctions, thereby substantiating the critical role of the IBN-PPARγ pathway in metabolite-mediated mucosal repair. Collectively, we delineate a prebiotic/probiotic–metabolite axis wherein P. goldsteinii facilitates mucosal repair via IBN/PPARγ-dependent epithelial metabolic reprogramming. This insight redefines antibiotic-resistant commensals as precise biotherapeutics for microbiota restoration in refractory UC management.
Obesity is a common health problem marked by the accumulation of excess body fat beyond the range characteristics of a healthy weight, affecting millions worldwide. Although advancements have been made in the realm of probiotic therapy for obesity, studies on the combined use of probiotics for the treatment of obesity have yet to be well explored. In this study, we investigated the potential of Parabacteroides goldsteinii ( P. goldsteinii ) and Bacteroides sartorii ( B. sartorii ) combinations and their microencapsulated forms for treating obesity. We identified different probiotic strains by 16S rRNA analysis in obese and healthy mice. The activity of these probiotics was evaluated in vitro under simulated gastrointestinal conditions. In vivo, the effects of probiotics on obese mice were assessed by monitoring body weight, glucose tolerance, colon integrity, and various molecular markers. Our results suggested that P. goldsteinii and B. sartorii were shown to be less abundant in obese mice ( P < 0.05). Compared with the control group mice, the obese phenotypes of the probiotics intervention group mice were significantly improved ( P < 0.05). Further results showed that compared with the control group mice, the expression of the FTO in the liver tissue of the probiotics intervention group mice was downregulated ( P < 0.05), while the expression of the Ampk gene was upregulated ( P < 0.05), indicating that probiotic intervention had reduced the expression of obesity-related genes in mice and had alleviated their obese condition. Furthermore, Microcapsule was remarkably effective in maintaining the viability of probiotics and facilitating their persistence, leading to a significant reduction in weight gain in mice compared with controls within just one week ( P < 0.05). Taken together, our study demonstrates that the intervention using the combination of P. goldsteinii and B. sartorii is more effective in treating obesity than using either probiotic alone. The encapsulation approach further enhances the anti-obesity efficacy of the combined probiotic mixture.
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