title: Improvement in glucose tolerance and insulin sensitivity by probiotic strains of Indian gut origin in high-fat diet-fed C57BL/6J mice.
abstract: OBJECTIVE
  Diabetes and obesity are characterized by glucose intolerance, fat deposition, inflammation, and dyslipidemia. Recent reports postulated that distinct gut microbiota alterations were observed in obese/diabetic subjects and modulating gut microbiota beneficially through specific probiotics could be a potential therapeutic option for type 2 diabetes/obesity. Therefore, we attempted to study the efficacy of probiotics of Indian gut origin (Lactobacillus plantarum MTCC5690 and Lactobacillus fermentum MTCC5689) along with a positive control, Lactobacillus rhamnosus (LGG) on glucose/lipid homeostasis in high-fat-diet-induced diabetic animal model.
  
  
  METHODS
  C57BL/6J male mice were divided into seven groups (n = 6 per group) comprising feeding on: (1) Normal Pellet Diet (NPD), (2) High-Fat Diet (HFD), (3) HFD with LGG, (4) HFD with MTCC5690, (5) HFD with MTCC5689, (6) HFD with metformin, and 7) HFD with vildagliptin for a period of 6 months. Biochemical markers, glucose tolerance, insulin resistance, and GLP-1 and LPS levels were assessed by standard protocols. Gut integrity was measured by intestinal permeability test. Transcriptional levels of tight junction proteins (TJPs) were probed in small intestinal tissues while inflammatory signals and other pathway specific genes were profiled in liver, visceral adipose tissue, and skeletal muscle.
  
  
  RESULTS
  Mice fed with HFD became insulin resistant, glucose intolerant, hyperglycemic, and dyslipidemic. Diabetic mice were characterized to exhibit decreased levels of GLP-1, increased gut permeability, increased circulatory levels of LPS, decrease in the gene expression patterns of intestinal tight junction markers (occludin and ZO-1), and increased proinflammatory gene markers (TNFα and IL6) in visceral fat along with decreased mRNA expression of FIAF and adiponectin. Diabetic mice also exhibited increased mRNA expression of ER stress markers in skeletal muscle. In addition, liver from HFD-fed diabetic mice showed increased gene expressions of proinflammation, lipogenesis, and gluconeogenesis. Probiotic interventions (most prominently the MTCC5689) resisted insulin resistance and development of diabetes in mice under HFD feeding and beneficially modulated all the biochemical and molecular alterations in a mechanistic way in several tissues. The metabolic benefits offered by the probiotics were also more or less similar to that of standard drugs such as metformin and vildagliptin.
  
  
  CONCLUSIONS
  Native probiotic strains MTCC 5690 and MTCC 5689 appear to have potential against insulin resistance and type 2 diabetes with mechanistic, multiple tissue-specific mode of actions.
authors.affiliation: Department of Cell and Molecular Biology, Dr. Rema Mohan High-Throughput Screening (HTS) Lab, Madras Diabetes Research Foundation and Dr. Mohan's Diabetes Specialties Centre, 4, Conran Smith Road, Gopalapuram, Chennai, 600 086, India.
authors.forename: Mahalingam
authors.initials: M
authors.lastname: Balakumar
authors.affiliation: Department of Cell and Molecular Biology, Dr. Rema Mohan High-Throughput Screening (HTS) Lab, Madras Diabetes Research Foundation and Dr. Mohan's Diabetes Specialties Centre, 4, Conran Smith Road, Gopalapuram, Chennai, 600 086, India.
authors.forename: Durai
authors.initials: D
authors.lastname: Prabhu
authors.affiliation: Department of Cell and Molecular Biology, Dr. Rema Mohan High-Throughput Screening (HTS) Lab, Madras Diabetes Research Foundation and Dr. Mohan's Diabetes Specialties Centre, 4, Conran Smith Road, Gopalapuram, Chennai, 600 086, India.
authors.forename: Chandrakumar
authors.initials: C
authors.lastname: Sathishkumar
authors.affiliation: Department of Cell and Molecular Biology, Dr. Rema Mohan High-Throughput Screening (HTS) Lab, Madras Diabetes Research Foundation and Dr. Mohan's Diabetes Specialties Centre, 4, Conran Smith Road, Gopalapuram, Chennai, 600 086, India.
authors.forename: Paramasivam
authors.initials: P
authors.lastname: Prabu
authors.affiliation: National Dairy Research Institute (NDRI), Karnal, Haryana, 132001, India.
authors.forename: Namita
authors.initials: N
authors.lastname: Rokana
authors.affiliation: Department of Cell and Molecular Biology, Dr. Rema Mohan High-Throughput Screening (HTS) Lab, Madras Diabetes Research Foundation and Dr. Mohan's Diabetes Specialties Centre, 4, Conran Smith Road, Gopalapuram, Chennai, 600 086, India.
authors.forename: Ramesh
authors.initials: R
authors.lastname: Kumar
authors.affiliation: Department of Cell and Molecular Biology, Dr. Rema Mohan High-Throughput Screening (HTS) Lab, Madras Diabetes Research Foundation and Dr. Mohan's Diabetes Specialties Centre, 4, Conran Smith Road, Gopalapuram, Chennai, 600 086, India.
authors.forename: Srividhya
authors.initials: S
authors.lastname: Raghavan
authors.affiliation: Department of Cell and Molecular Biology, Dr. Rema Mohan High-Throughput Screening (HTS) Lab, Madras Diabetes Research Foundation and Dr. Mohan's Diabetes Specialties Centre, 4, Conran Smith Road, Gopalapuram, Chennai, 600 086, India.
authors.forename: Avinash
authors.initials: A
authors.lastname: Soundarajan
authors.affiliation: National Dairy Research Institute (NDRI), Karnal, Haryana, 132001, India.
authors.forename: Sunita
authors.initials: S
authors.lastname: Grover
authors.affiliation: National Dairy Research Institute (NDRI), Karnal, Haryana, 132001, India.
authors.forename: Virender Kumar
authors.initials: VK
authors.lastname: Batish
authors.affiliation: Department of Cell and Molecular Biology, Dr. Rema Mohan High-Throughput Screening (HTS) Lab, Madras Diabetes Research Foundation and Dr. Mohan's Diabetes Specialties Centre, 4, Conran Smith Road, Gopalapuram, Chennai, 600 086, India.
authors.forename: Viswanathan
authors.initials: V
authors.lastname: Mohan
authors.affiliation: Department of Cell and Molecular Biology, Dr. Rema Mohan High-Throughput Screening (HTS) Lab, Madras Diabetes Research Foundation and Dr. Mohan's Diabetes Specialties Centre, 4, Conran Smith Road, Gopalapuram, Chennai, 600 086, India. balusignal@gmail.com.
authors.forename: Muthuswamy
authors.initials: M
authors.lastname: Balasubramanyam
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D003921:Diabetes Mellitus, Experimental; D003924:Diabetes Mellitus, Type 2 / Q000517:prevention & control*; D059305:Diet, High-Fat; D050171:Dyslipidemias / Q000517:prevention & control; D059865:Endoplasmic Reticulum Stress / Q000235:genetics; D000069196:Gastrointestinal Microbiome; D052216:Glucagon-Like Peptide 1 / Q000097:blood; D005943:Gluconeogenesis / Q000235:genetics; D018149:Glucose Intolerance / Q000517:prevention & control*; D007194:India; D007249:Inflammation / Q000235:genetics; D007333:Insulin Resistance; D052197:Limosilactobacillus fermentum; D048191:Lactiplantibacillus plantarum; D008055:Lipids / Q000097:blood; D050155:Lipogenesis / Q000235:genetics; D008070:Lipopolysaccharides / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019936:Probiotics / Q000627:therapeutic use*; D059467:Transcriptome
chemical_list: D001786:Blood Glucose; D008055:Lipids; D008070:Lipopolysaccharides; D052216:Glucagon-Like Peptide 1
keywords: High-fat diet; Insulin resistance; LGG; LPS; Lactobacillus fermentum MTCC 5689; Lactobacillus plantarum MTCC 5690; Probiotics; Tight junction protein; Type 2 diabetes