Renée Wilson, Registered Dietitian and PhD Candidate at University of Otago, New Zealand. Presented at the 1st International Symposium on Kiwifruit and Health: http://www.kiwifruitsymposium.org/presentations/diet-microbiota-and-metabolic-health/ This cross-sectional pilot study aims to determine whether or not there are any differences between the gut microbiota of people with normal glucose tolerance, pre-diabetes and type 2 diabetes.

1. Diet, Microbiota and Metabolic Health
Renée Wilson, PhD Candidate & Registered Dietitian
Supervisors: Dr Jinny Willis, Professor Richard Gearry,
Professor Gerald Tannock, Dr Paula Skidmore

2. The Human Microbiota

3. Human versus Microbial Cells
Semenkovich et al, Diabetes, 2015, 1-11

4. Genes and Genetic Variation
Semenkovich et al, Diabetes, 2015, 1-11

5. The Gut Microbiota

6. Classification
• Bacteroidetes
• Firmicutes
• Actinobacteria
• Proteobacteria
• Verrucomicrobia

7. Colonisation of the Gut Microbiota
• Colonisation
Mode of delivery
Breast vs formula feed (DIET)
Environment
Drug therapies
• 3 years for an adult-like microbiome.

8. The large bowel is a fermenter
(continuous culture; chemostat)
IN: indigestible components
of food
OUT: waste and bacteria
Fermentation
Calories
Endogenous substrates
Gases
“gut microbes represent an extended
reservoir of metabolic capabilities”
Owyang and Wu, 2014

9. How we Study the Microbiota
We have been interested in the gut microbiota since the 1900’s.
However, culture based methods have limitations!
Culture-independent sequencing based methods were developed in the
90’s.

10. Bioinformatics

11. The Gut Microbiota and Metabolic Health
Diabetes
Obesity
IBD
Allergic diseases
Mental health

14. Previous Research Limitations
• Different study populations
Small sample sizes
Heterogeneous populations (lack of age and gender balance)
• Methodological issues
Variety of methods for characterizing gut microbiota - comparisons
between studies difficult
• Incomplete data on diabetes medication
• Limited data on dietary intake and physical activity

15. Heterogeneity of Phenotype in Clinical Cohorts
Sato et al, 2014

16. Diabetes
• There are 3 main types of diabetes:
– type 1 diabetes mellitus (T1DM)
– type 2 diabetes mellitus (T2DM)
– gestational diabetes.
• Poorly managed diabetes leads to serious complications and early
death.

17. Type 2 Diabetes Mellitus
• T2DM comprises 90% of people with diabetes around the world.
• In T2DM, either the body doesn’t produce enough insulin, or the
cells in the body don’t recognise the insulin that is present. The end
result is high levels of glucose in your blood (IDF, 2015).
• For many people (but not all) it can be prevented through following a
healthy lifestyle.
• There is a clear link between T2DM and overweight/obesity,
hypertension and dyslipidaemia i.e. the Metabolic Syndrome.

18. Diabetes around the World

19. Diabetes: A Global Emergency

20. Diabetes in New Zealand
Data are % (95% CI) Coppell et al, NZMJ, 2013

23. Current Research Study
Cross-sectional pilot study.
To determine whether or not there are any differences between the gut
microbiota with normal glucose tolerance (NGT), pre-diabetes and T2DM.
– Define gut microbiota composition associated with NGT, pre-diabetes and
T2DM.
– Identify dietary associations with gut microbiota composition with particular
emphasis on fruit and vegetables intake.
– Establish the feasibility of an intervention study with kiwifruit to favourably
alter gut microbiota composition and therefore impact on glucose tolerance.

24. Study Groups
Normoglycaemia (n=30)
Pre-diabetes (n=20)
Adults > 18 yrs
Type 2 Diabetes (n=20) - Metformin only

25. Data and Sample Collection
• Questionnaires
• Blood, urine, stool sample
• 4 day weighed food diary
• Anthropometric data

26. Benefits and Outcomes
• Relationships between glucose tolerance, dietary intake, gut
microbiota characteristics and urine metabolite profiles.
• An indication whether a dietary intervention to alter gut microbiota
provides a feasible prospect for type 2 diabetes therapy.

27. Diet and the Microbiota
De Filippo et al, PNAS, 2010; 14691-14696

28. Loss of Microbial DiversityLoss of microbial diversity

29. Diet and the MicrobiotaDiet and the Gut

30. Manipulation of the Gut Microbiota
• Prebiotic
• Probiotic
• Antibiotic
• Faecal microbiota transplant

31. Prebiotic Research
What is a prebiotic?
A prebiotic is a type of fibre that passes through the GI tract undigested
and stimulates the growth and/or activity of certain ‘good’ bacteria in the
large intestine.
E.g. Prebiotics include inulin and galacto-oligosachairdes

32. Probiotics
• "live micro-organisms which, when administered in adequate
amounts, confer a health benefit on the host“ (WHO, 2001)
• May enhance barrier function, compete with pathogens, modulate
immune function.

33. Antibiotics
• Kill bacteria.
• Antibiotics have been found to alter the human gut microbiota, with
effects that are rapid and sometimes persistent.
• Differing rates of antibiotic use worldwide.
• Bacteria can become resistant to antibiotics.

34. Faecal microbiota transplant
Faecal transplant

35. Microbial Population
Diet
Antibiotic use Host genome
Hygiene
SCFA
Production
Increased
energy harvest
Obesity
Pre-diabetes
Type 2
Diabetes
Gut
Permeability
Inflammation
Weight gain/
↑insulin
resistance
Impaired
insulin &
glucose
tolerance