Improvement in glucose tolerance and insulin sensitivity by probiotic strains of Indian gut origin in high-fat diet-fed C57BL/6J mice

• Published in: European journal of nutrition Vol. 57; no. 1; pp. 279 - 295
• Main Authors: Balakumar, Mahalingam, Prabhu, Durai, Sathishkumar, Chandrakumar, Prabu, Paramasivam, Rokana, Namita, Kumar, Ramesh, Raghavan, Srividhya, Soundarajan, Avinash, Grover, Sunita, Batish, Virender Kumar, Mohan, Viswanathan, Balasubramanyam, Muthuswamy
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.02.2018; Springer Nature B.V
• Subjects: Adiponectin; Adipose tissue; animal disease models; Animals; Biochemical markers; biomarkers; Blood Glucose - analysis; Chemistry; Chemistry and Materials Science; Diabetes; Diabetes mellitus; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2 - prevention & control; Diet, High-Fat; Digestive system; Dyslipidemia; Dyslipidemias - prevention & control; Endoplasmic Reticulum Stress - genetics; Feeding; Gastrointestinal Microbiome; Gastrointestinal tract; Gene expression; gene expression regulation; genes; glucagon-like peptide 1; Glucagon-Like Peptide 1 - blood; Gluconeogenesis; Gluconeogenesis - genetics; Glucose; Glucose Intolerance - prevention & control; Glucose tolerance; High fat diet; Homeostasis; hyperlipidemia; India; Inflammation; Inflammation - genetics; Insulin; Insulin Resistance; Interleukin 6; Intestinal microflora; intestinal microorganisms; Intestine; intestines; Intolerance; Lactobacillus fermentum; Lactobacillus plantarum; Lactobacillus rhamnosus; lipids; Lipids - blood; Lipogenesis; Lipogenesis - genetics; Lipopolysaccharides; Lipopolysaccharides - blood; Liver; Male; males; mechanism of action; messenger RNA; metformin; Mice; Mice, Inbred C57BL; Microbiota; Musculoskeletal system; noninsulin-dependent diabetes mellitus; Nutrition; obesity; occludins; Original Contribution; Permeability; Probiotics; Probiotics - therapeutic use; Rodents; Skeletal muscle; tight junctions; Transcription; transcription (genetics); Transcriptome; tumor necrosis factor-alpha; visceral fat; Type 2 diabetes; Probiotics; MTCC 5689; High-fat diet; Insulin resistance; MTCC 5690; Tight junction protein; LGG; LPS; Lactobacillus fermentum MTCC 5689; Lactobacillus plantarum MTCC 5690
• ISSN: 1436-6207; 1436-6215; 1436-6215
• DOI: 10.1007/s00394-016-1317-7

Purpose 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. Conclusion 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.