解析梭状芽胞杆菌对高脂肪饮食诱导肥胖 C57BL/6 小鼠的益生菌作用的代谢产物和生物标志物的特征。
Characterization of metabolites and biomarkers for the probiotic effects of Clostridium cochlearium on high-fat diet-induced obese C57BL/6 mice.
机构信息
Department of Nutrition and Food Science, Wayne State University, Detroit, MI, 48202, USA.
Byrdine F. Lewis College of Nursing and Health Professions, Georgia State University, Atlanta, GA, 30303, USA.
出版信息
Eur J Nutr. 2022 Jun;61(4):2217-2229. doi: 10.1007/s00394-022-02840-z. Epub 2022 Mar 20.
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.
目的
丁酸产生菌的益生菌种已被研究用于预防和治疗肥胖和超重。然而， Cochlearium 梭菌尚未与任何健康益处相关联。我们假设 Cochlearium 梭菌可能是一种有前途的新益生菌，具有改善体重控制和胰岛素敏感性的健康益处。
方法
通过 NMR 和 GC-MS 分析对 Cochlearium 梭菌的短链脂肪酸（SCFA）产量进行了表征。通过饮食诱导肥胖（DIO）C57BL/6 小鼠评估 Cochlearium 梭菌的益生菌作用。使用 GC-MS 测量 Cochlearium 梭菌给药对肠道 SCFA 的影响。基于 LC-MS 的非靶向代谢组学分析和多变量分析用于评估血清代谢变化，鉴定对 Cochlearium 梭菌给药的反应中的生物标志物和途径。
结果
经过 17 周的饮食干预，CC 组（喂食高脂肪饮食并补充 Cochlearium 梭菌）的体重增加量比高脂肪饮食（HF）对照组减少了 21.86%（P<0.001），这具体反映在明显降低的脂肪量（CC 与 HF，17.19g 与 22.86g，P<0.0001）和脂肪百分比（CC 与 HF，41.25%与 47.10%，P<0.0001），以及增加的瘦体百分比（CC 与 HF，46.63%与 43.72%，P<0.05）。Cochlearium 梭菌给药从第 8 周开始显著降低空腹血糖（P<0.05 或 0.01），最终改善了胰岛素敏感性（HOMA-IR，CC 与 HF，63.77 与 143.13，P<0.05）。在 CC 组的肠道内容物中观察到 SCFA 水平总体降低。代谢组学分析能够在 CC 和 HF 组之间鉴定出 53 种有区别的代谢物和 24 种改变的途径。特别是，大多数与体重呈正相关的途径匹配代谢物包括谷氨酸、苯丙氨酸、鸟氨酸、PCs、LPCs、AcCas、脯氨酸、5,6-二氢尿嘧啶、焦谷氨酸和 1-吡咯啉-4-羟基-2-羧酸。
结论
Cochlearium 梭菌的有益作用可能与其恢复某些肥胖驱动的生物标志物和途径的能力有关，特别是下调与特定氨基酸、PCs、LPCs 和 AcCas 相关的途径。需要进一步研究以调查相关代谢物和代谢途径。Cochlearium 梭菌可能被开发为预防或缓解人类肥胖和糖尿病的有前途的新型益生菌。
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