Is Sugar a New Fat: Genetics, Environment
and Gut Microbiota Perspective
Safarina G. Malik
Lembaga Biologi Molekuler Eijkman
Jl Diponegoro 69, Jakarta 10430
Indonesia
Dynamic relationship:
gene-environment-development
See: Simopoulos, Annu Rev Public Health, 2010
2
Nutritio
n
Lifestyle
Culture
Econom
y
Social
Infuence of genotype on the response to a
caloric restriction program (nutrigenetics)
and the efect of caloric restriction on gene
expression (nutrigenomics)
Lifestyle and obesity
•
Industrialization has changed lifestyle, diet, and
health of individuals living in urban areas
•
Correlated with the rise of obesity and the number
of associated deaths
•
Lifestyle
modifications aim to reduce the burden
of
obesity
and reduce the associated conditions
Genetic association with adiposity
appeared to be more pronounced with
greater intake of sugar-sweetened
beverages
Sugary drinks in the pathogenesis of obesity
and cardiovascular diseases
08/11/2017 Glucose; 6
Fructose
Changes in water and beverage intake and
long-term weight changes
08/11/2017 Pan et al, Int J Obes 7
Non-caloric artificial (NAS)
sweeteners and the microbiome:
findings and challenges
08/11/2017 8
NAS-Bacteria
interactions
Diverse infuences on the epidemic
lifestyle disease – what to do and how?
Host Factors
(Genetic
background,
immunological
state)
Socio-economic, environment
(in-utero exposure, diet,
pharmaceuticals, exercise)
Gut Microbiota
(composition,
activity)
Human
Health
The problem:
An
epidemic of obesity
driven by lifestyle
change.
Greater understanding of the tripartite infuence of on
the host state is needed
IMELDA
:
Indonesian Model for Epidemic Lifestyle Disease
Associations
Bali in transition: 30 years ago
economy was largely
agricultural-based
Islet in the terraced rice fields of Bali, Indonesia. Photo copyright: Yann Arthus-Bertrand.
From the postcard book THE EARTH FROM THE AIR
Bali in transition: today tourism is
the largest single industry in Bali
Rice fields were converted to villas and cottages, souvenir
Why study the Balinese?
1. Impact of lifestyle changes
for the Balinese (urban vs
rural environment)
2. Susceptibility gene(s)
associated with disease traits
3. Genes-environment
interaction in infuencing
disease manifestation
The Bali Study: Genes-environment
interactions – demonstrated diferences
metabolism in urban vs rural
Variable
Urban
Rural
P-value
N
580
492
Age (years)
43.4
12.7
45.6
16.6
0.110
BMI
(kg/m2)
24.1
4.6 21.7
4.0
<0.001
WC (cm)
89.2
9.8
76.9
10.4
<0.001
SBP
(mmHg)
117.3
16.8
119.4
18.6
0.061
DBP
(mmHg)
76.4
10.8
76.3
11.2
0.845
FPG (mg/dl)
93.6
30.1
99.2
37.4
<0.001
TG (mg/dl)
139.1
84.7
115.4
57.9
<0.001
HDL
(mg/dl)
52.0
12.5
55.6
12.2
<0.001
LDL (mg/dl)
119.5
31.6
124.8
31.9
0.005
TC (mg/dl)
194.2
36.0
199.7
37.7
0.018
Suastika et al, 2011; Saraswati et al, 2011; Malik et al, 2011; Oktavianthi
Bali
North Kalimantan
Mt. Kidul
West Sumba
Biometric s (incl.
BMI)
Fecal Microbiot
a
Diet Data
40 samples:
All females, Age 18 – 27
Febinia CA et al, manuscript in prep
16/11/2017 14
The IMELDA Project:
MtDNA genetic background is
associated with waist-hip biometrics
MtDNA macro-haplogroup M: higher WC and
WHR
Febinia CA et al, manuscript in prep16/11/2017 16
Famil y
Balinese gut microbiota: 2 types of
communities
Associations of Balinese gut
microbiota with mtDNA and obesity
Balinese gut microbiota is associated with mtDNA haplotype
Prevotella-type in Balinese gut microbiota is associated with obesity
16/11/2017 17
T2 Cluster
T1 Cluster
Prevotella
Bacteroides
Rank-based Linear Models
Balinese (n = 40) Estimate Std. Error t.value p.value
Carbohydrate (% kcal)
(Intercept) 43.74319 4.62134 9.4655 < 0.001
Prevotella 0.15099 0.17701 0.853 0.39916
Bacteroides 0.31629 0.15856 1.9947 0.05348
Fat (% kcal)
(Intercept) 36.604416 4.871993 7.5132 < 0.001
Prevotella -0.034228 0.170677 -0.2005 0.84215
Bacteroides -0.300355 0.152888 -1.9645 0.05701
Protein (% kcal)
(Intercept) 19.400851 1.540659 12.5926 < 0.001
Prevotella -0.150416 0.062606 -2.4026 0.02141
Bacteroides -0.044671 0.056081 -0.7965 0.4308
Diet diferences
by Obesity
Diet Association
with Microbiota
lean obese obese vs.
lean
Diet Components (n = 38) (n = 8) p-value
% kcal
Carbohydrate 51 ± 11 53 ± 13 0.692
% kcal Fat 30 ± 11 32 ± 13 0.723
% kcal Protein 19 ± 5 15 ± 3 0.035
Protein Intake Ratio in Balinese is Associated with
Obesity
and
Prevotella
abundance
SUMMARY
•
Obesity is tightly linked to interaction of genetics with
environment
•
An epidemic of obesity is driven by lifestyle changes –
increase intake of sugar
•
Gut microbiota might be infuenced by genetic
background
•
There is an indication of gut microbiota infuence on
obesity
•
Gut microbiota is modulated by diet, including sugar,
that in turn will infuence general health
•
Greater understanding of the tripartite (host factors,
socio-economic-environment, gut microbiota)
infuence on the host state is needed
Acknowledgement
08/11/2017
Eijkman Institute for Molecular Biology
Hidayat Trimarsanto
Clarissa A. Febinia
Sukma Oktavianthi
Herawati Sudoyo
Lidwina Priliani, MSc
Ria Hasnita
Artricia Rasyid
Rut C. Inggriani
Asri Sulfianti
Rahma Fitri Hayati
Faculty of Medicine, Udayana University
Ketut Suastika
Made Ratna Saraswati
I Wayan Weta
Desak Made Wihandani
Pande Dwipayana
Students of Faculty of Medicine
Faculty of Public Health, Universitas Indonesia
Ratna Djuwita Hatma
Rizka Maulida Charles Perkins Centre, the University
of Sydney
Gene hunter @ Eijkman Institute
