Characterization of metabolites and biomarkers for the probiotic effects of Clostridium cochlearium on high-fat diet-induced obese C57BL/6 mice

Purpose Probiotic species of butyrate producers have been investigated for the potential in preventing and treating obesity and overweight. However, Clostridium cochlearium has not been linked with any health benefits. We hypothesized that C. cochlearium could be a promising new probiotic with health benefits in improving body weight control and insulin sensitivity. Methods Productions of short-chain fatty acids (SCFAs) were characterized for C. cochlearium by NMR and GC-MS analyses. Probiotic effects of C. cochlearium were evaluated through diet-induced obese (DIO) C57BL/6 mice. The influence of C. cochlearium administration on gut SCFAs was measured using GC-MS. LC-MS-based untargeted metabolomic profiling and multivariate analysis were used to assess the serum metabolic alteration, identify biomarkers and pathways in response to the C. cochlearium administration. Results After 17 weeks of diet intervention, body weight gain of CC group (fed with a high-fat diet supplemented with C. cochlearium) showed a 21.86% reduction from the high-fat diet (HF) control group (P < 0.001), which was specifically reflected on the significantly lowered fat mass (CC vs HF, 17.19 g vs 22.86 g, P < 0.0001) and fat percentage (CC vs HF, 41.25% vs 47.10%, P < 0.0001), and increased lean percentage (CC vs HF, 46.63% vs 43.72%, P < 0.05). C. cochlearium administration significantly reduced fasting blood glucose from week 8 (P < 0.05 or 0.01), and eventually improved insulin sensitivity (HOMA-IR, CC vs HF, 63.77 vs 143.13, P < 0.05). Overall lowered levels of SCFAs were observed in the gut content of CC group. Metabolomic analysis enabled the identification of 53 discriminatory metabolites and 24 altered pathways between CC and HF groups. In particularly, most of the pathway-matched metabolites showed positive correlations with body weight, which included glutamate, phenylalanine, ornithine, PCs, LPCs, AcCas, proline, 5,6-dihydrouracil, pyroglutamic acid, and 1-pyrroline-4-hydroxy-2-carboxylate. Conclusions The beneficial effects of C. cochlearium could be related to its ability to restore certain obesity-driven biomarkers and pathways, especially downregulating pathways related to specific amino acids, PCs, LPCs and AcCas. Further research is warranted to investigate related metabolites and metabolic pathways. C. cochlearium may be developed as a promising new probiotic for the prevention or alleviation of obesity and diabetes in human.

Automated summary

The study found that utilizing Clostridium cochlearium as a probiotic can significantly reduce weight gain caused by a high-fat diet, decrease fat mass, and improve insulin sensitivity. Additionally, Clostridium cochlearium can also improve obesity-related metabolic abnormalities by regulating specific metabolic pathways and biomarkers. Further research is needed to explore the related metabolites and metabolic pathways, suggesting Clostridium cochlearium has the potential to be developed as a promising new probiotic for preventing or alleviating obesity and diabetes in humans.