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从婴儿粪便中分离出的乳酸杆菌菌株对肠道α-和β-葡萄糖苷酶具有强大的抑制活性,表明其具有抗糖尿病潜力。

Lactobacillus strains isolated from infant faeces possess potent inhibitory activity against intestinal alpha- and beta-glucosidases suggesting anti-diabetic potential.

作者信息

Panwar Harsh, Calderwood Danielle, Grant Irene R, Grover Sunita, Green Brian D

机构信息

Institute for Global Food Security, School of Biological Sciences, Queen's University Belfast, David Keir Building, Stranmillis Road, Belfast, BT9 5AG, UK.

出版信息

Eur J Nutr. 2014 Oct;53(7):1465-74. doi: 10.1007/s00394-013-0649-9. Epub 2014 Jan 12.

Abstract

PURPOSE

Inhibitors of intestinal alpha-glucosidases are used therapeutically to treat type 2 diabetes mellitus. Bacteria such as Actinoplanes sp. naturally produce potent alpha-glucosidase inhibitor compounds, including the most widely available drug acarbose. It is not known whether lactic acid bacteria (LAB) colonising the human gut possess inhibitory potential against glucosidases. Hence, the study was undertaken to screen LABs having inherent alpha- and beta-glucosidase inhibitory potential.

METHODS

This study isolated, screened, identified and extracted Lactobacillus strains (Lb1-15) from human infant faecal samples determining their inhibitory activity against intestinal maltase, sucrase, lactase and amylase. Lactobacillus reference strains (Ref1-7), a Gram positive control (Ctrl1) and two Gram negative controls (Ctrl2-3), were also analysed to compare activity.

RESULTS

Faecal isolates were identified by DNA sequencing, with the majority identified as unique strains of Lactobacillus plantarum. Some strains (L. plantarum, L. fermentum, L. casei and L. rhamnosus) had potent and broad spectrum inhibitory activities (up to 89%; p < 0.001; 500 mg/ml wet weight) comparable to acarbose (up to 88%; p < 0.001; 30 mg/ml). Inhibitory activity was concentration-dependent and was freely available in the supernatant, and was not present in other bacterial genera (Bifidobacterium bifidum and Escherichia coli or Salmonella typhimurium). Interestingly, the potency and spectrum of inhibitory activity across strains of a single species (L. plantarum) differed substantially. Some Lactobacillus extracts had broader spectrum activities than acarbose, effectively inhibiting beta-glucosidase activity (lactase) as well as alpha-glucosidase activities (maltase, sucrase and amylase). Anti-diabetic potential was indicated by the fact that oral gavage with a L. rhamnosus extract (1 g/kg) was able to reduce glucose excursions (Area under curve; 22%; p < 0.05) in rats during a carbohydrate challenge (starch; 2 g/kg).

CONCLUSION

These results definitively demonstrate that Lactobacillus strains present in the human gut have alpha- and beta-glucosidase inhibitory activities and can reduce blood glucose responses in vivo. Although the potential use of LAB such as Lactobacillus as a dietary supplement, medicinal food or biotherapeutic for diabetes is uncertain, such an approach might offer advantages over drug therapies in terms of broader spectrum activities and fewer unpleasant side effects. Further characterisation of this bioactivity is warranted, and chronic studies should be undertaken in appropriate animal models or diabetic subjects.

摘要

目的

肠道α-葡萄糖苷酶抑制剂可用于治疗2型糖尿病。诸如游动放线菌属等细菌能天然产生强效α-葡萄糖苷酶抑制化合物,其中包括应用最为广泛的药物阿卡波糖。目前尚不清楚定殖于人类肠道的乳酸菌是否具有对葡萄糖苷酶的抑制潜力。因此,开展了本研究以筛选具有内在α-和β-葡萄糖苷酶抑制潜力的乳酸菌。

方法

本研究从人类婴儿粪便样本中分离、筛选、鉴定并提取了乳酸杆菌菌株(Lb1 - 15),测定其对肠道麦芽糖酶、蔗糖酶、乳糖酶和淀粉酶的抑制活性。还分析了乳酸杆菌参考菌株(Ref1 - 7)、一株革兰氏阳性对照(Ctrl1)和两株革兰氏阴性对照(Ctrl2 - 3)以比较活性。

结果

通过DNA测序鉴定粪便分离株,大多数被鉴定为植物乳杆菌的独特菌株。一些菌株(植物乳杆菌、发酵乳杆菌、干酪乳杆菌和鼠李糖乳杆菌)具有强效且广谱的抑制活性(高达89%;p < 0.001;500 mg/ml湿重),与阿卡波糖相当(高达88%;p < 0.001;30 mg/ml)。抑制活性呈浓度依赖性,且可自由存在于上清液中,在其他细菌属(双歧双歧杆菌、大肠杆菌或鼠伤寒沙门氏菌)中不存在。有趣的是,单一物种(植物乳杆菌)不同菌株间的抑制活性效力和谱存在显著差异。一些乳酸杆菌提取物具有比阿卡波糖更宽的活性谱,能有效抑制β-葡萄糖苷酶活性(乳糖酶)以及α-葡萄糖苷酶活性(麦芽糖酶、蔗糖酶和淀粉酶)。用鼠李糖乳杆菌提取物(1 g/kg)经口灌胃能够降低大鼠在碳水化合物激发试验(淀粉;2 g/kg)期间的血糖波动(曲线下面积;22%;p < 0.05),这表明其具有抗糖尿病潜力。

结论

这些结果明确表明,人类肠道中存在的乳酸杆菌菌株具有α-和β-葡萄糖苷酶抑制活性,并能在体内降低血糖反应。尽管将诸如乳酸杆菌等乳酸菌作为糖尿病的膳食补充剂、药用食品或生物治疗剂的潜在用途尚不确定,但这种方法在活性谱更宽和不良副作用更少方面可能比药物治疗具有优势。有必要对这种生物活性进行进一步表征,并且应在合适的动物模型或糖尿病受试者中开展长期研究。

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