probiotics in diabetes treatment by tariful
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Probiotic in Diabetes Treatment: - Effective Identification of Probiotic Bacteria Isolated from Regional Biota
Tariful IslamSenior Officer
Biotechnology Derived Product FacilityIncepta Pharmaceuticals Ltd
1st International Conference DRUG DISCOERY & DEVELOPMENT RESEARCH IN DEVELOPING COUNTRIES (DRDC)
4th October,2015 1
Elie Metchnikoff (1885 – 1916)
• First described by Metchnikoff in 1908 as “Live microbial food ingredients that alter the microflora and confer health benefit”
• “Live microorganisms which when administered in adequate amounts confer a health benefit on the host” (FAO/WHO)
Probiotics
Probiotics Research Trends
1761
91
191
453432
564
307
271
127
421
294
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
2008
Number of Published Clinical Studies on Probiotic
Source: www.ncbi.nlm.nih.gov/pubmed 3
Research Publications on Probiotic
Gut functionAcute diarrheaTravelers diarrhea
AllergyAtopic dermatitisAsthma
Oral microbiologyDental caries
Colds, respiratory infections
Skin microbiology, inflammation
CNS
Metabolic syndromeDiabetes Obesity
Probiotics - Biological Swiss Army Knife
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Classification of Probiotic Bacteria
Probiotic Bacteria
Lactobacillus Bifidobacterium Enterococcus
L. casei group L. acidophilus group
L. reuteri/ L. fermentum group
L. caseiL. paracasei
L. zeaeL. rahmnosus
5Georgieva et al. (2014)
~ 200-230bp ~ 198-210bp
~1500bp ~ 2900bp ~ 100bp
16S 23S 5S
Identification of Lactobacillus paracasei
rRNA Intergenic Spacer Regions
6
M
Genomic DNA of L. paracasei
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Identification of Lactobacillus paracasei
M M
8
Lp1
Identification of Lactobacillus paracasei
Sequencing of 16S-23S ISR rRNA Amplified Region of L. paracasei
9
Environmental Factors HFD Stress Life Style
Altered Microbiota
Increased Intestinal
Permeability
LPS
Activation of TLR-4
Cytokine Release
Interruption in Insulin
receptor’s activity
T1D/T2D
Destruction of pancreatic β- cell
Diabetes and Gut Microbiota
10
Insulin Resistance in Presence of LPS
Golgi
(signal)
-P -
Obstacle in glucose
transport
Glucose
Insulin receptor
Insulin
P
Insulin binding and signal transduction
GLUT4
LPS binding with TLR-4
T2D
11
Probiotic Treatment for T2D
12Gomes et al. (2014)
GLP-1
Insulin secretion
L-cell
Butyrate
Butyrate Producing Bacteria (Probiotics)
Treatment for T1D
13
Potential probiotic bacteria
Identification at molecular
level
Selection of identified
probiotic bacteria for diabetes treatment
In-vitro and In-vivo test for
effectiveness
Fermentation (R&D Scale)
Cell separation Lyophilization (R&D scale)
Formulation & Clinical trial
Final Product
Development Pathway of Probiotic Formulation for Diabetes Treatment
14
Importance of Microbiota
15
State of the art facility of Incepta Pharmaceuticals Ltd
Our Strength
16
Bio-safety Cabinet class II,
PCR machine, Applied Biosystems, USA/Germany.
Gel Electrophoresis apparatus, BioRad, USA.
Gel Documentation System, Cell Biosystem, USA
Fermenter (Bioreactor), New Brunswick, Eppendorf, USA
Lyophilizer (Vertis, USA)
Animal House
Our Strength
17
•Ahmed FE. Genetically modified probiotics in foods. Trends Biotechnol 2003;21:491–497•Alipio Z, Liao W, Roemer EJ, et al. Reversal of hyperglycemia in diabetic mouse models using induced-pluripotent stem (iPS)-derived pancreatic beta-like cells. Proc Natl Acad Sci U S A 2010;107:13426–13431 •Daniel C, Repa A, Wild C, et al. Modulation of allergic immune responses by mucosal application of recombinant lactic acid bacteria producing the major birch pollen allergen Bet v 1. Allergy 2006;61:812–819 •Ferber S, Halkin A, Cohen H, et al. Pancreatic and duodenal homeobox gene 1 induces expression of insulin genes in liver and ameliorates streptozotocin induced hyperglycemia. Nat Med 2000;6:568–572 •Georgieva . M., Andonova . L., Peikova L., Zlatkov. Al., Probiotics – health benefits, classification, quality assurance and quality control – review, PHARMACIA, vol. 61, No. 4/2014•Gomes AC, Bueno AA, Souza RGM, and Mota JF, Gut microbiota, probiotics and diabetes, Nutrition Journal, 2014, 13:60•Honi U, Sabrin F, Islam T, et al. Enzymatic activity and antibiotic resistance profile of Lactobacillus paracasei ssp. paracasei-1 isolated from regional yogurts of Bangladesh, J. Microbiol. Biotechnol. Food Sci., 2013, 3, 3, 235-239 •Islam T, Khan MI, Hossain MS, et al. Effective differentiation of Lactobacillus paracasei from Lactobacillus casei group, Open Life Sci. 2015 (Received) •Islam T, Sabrin F, Islam ME, et al. Analysis of antimicrobial activity of Lactobacillus paracasei ssp. paracasei-1 isolated from regional yogurt, Int. Res. J. Appl. Life Sci., 2012, 1, 4, 66-72 •Kuehn MJ. Genetically engineered probiotic competition. Gastroenterology 2006;130:1915–1916 •Noguchi H. Stem cells for the treatment of diabetes. Endocr J 2007;54:7–16 •Soria B, Roche E, Berná G, León-Quinto T, Reig JA, Martín F. Insulin-secreting cells derived from embryonic stem cells normalize glycemia in streptozotocin- induced diabetic mice. Diabetes 2000;49:157–162 •Suzuki A, Nakauchi H, Taniguchi H. Glucagon-like peptide 1 (1-37) converts intestinal epithelial cells into insulin-producing cells. Proc Natl Acad Sci U S A 2003;100:5034–5039 •Yadav H, Lee JH, Lloyd J, et al. Beneficial metabolic effects of a probiotic via butyrate induced GLP-1 secretion. J Biol Chem 2013 •Zalzman M, Gupta S, Giri RK, et al. Reversal of hyperglycemia in mice by using human expandable insulin-producing cells differentiated from fetal liver progenitor cells. Proc Natl Acad Sci U S A 2003;100:7253–7258
References
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Thank You
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