title: Lactobacillus strains isolated from infant faeces possess potent inhibitory activity against intestinal alpha- and beta-glucosidases suggesting anti-diabetic potential.
abstract: OBJECTIVE
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institute for Global Food Security, School of Biological Sciences, Queen's University Belfast, David Keir Building, Stranmillis Road, Belfast, BT9 5AG, UK.
authors.forename: Harsh
authors.initials: H
authors.lastname: Panwar
authors.forename: Danielle
authors.initials: D
authors.lastname: Calderwood
authors.forename: Irene R
authors.initials: IR
authors.lastname: Grant
authors.forename: Sunita
authors.initials: S
authors.lastname: Grover
authors.forename: Brian D
authors.initials: BD
authors.lastname: Green
mesh_terms: D020909:Acarbose / Q000378:metabolism; D000681:Amylases / Q000037:antagonists & inhibitors; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D004269:DNA, Bacterial / Q000302:isolation & purification; D003924:Diabetes Mellitus, Type 2 / Q000628:therapy; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005243:Feces / Q000382:microbiology*; D065089:Glycoside Hydrolase Inhibitors / Q000494:pharmacology*; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007223:Infant; D007422:Intestines / Q000201:enzymology / Q000382:microbiology*; D043322:Lactase / Q000037:antagonists & inhibitors; D007778:Lactobacillus / Q000145:classification / Q000302:isolation & purification*; D019936:Probiotics; D051381:Rats; D017207:Rats, Sprague-Dawley; D017422:Sequence Analysis, DNA; D013393:Sucrase / Q000037:antagonists & inhibitors; D000520:alpha-Glucosidases / Q000378:metabolism; D001617:beta-Glucosidase / Q000037:antagonists & inhibitors*
chemical_list: D001786:Blood Glucose; D004269:DNA, Bacterial; D004791:Enzyme Inhibitors; D065089:Glycoside Hydrolase Inhibitors; D007004:Hypoglycemic Agents; D000681:Amylases; D043322:Lactase; D000520:alpha-Glucosidases; D001617:beta-Glucosidase; D013393:Sucrase; D020909:Acarbose