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8/11/2019 NAS induced glucose intolerance
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Artificial sweeteners inducglucose intolerance by alterithe gut microbiota
Jotham Suez et al
BY
L.P.Ashwanth
8/11/2019 NAS induced glucose intolerance
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OVERVIEW
Background
Introduction
Tests and Results
Conclusion
Discussion
Reference
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BACKGROUND
Definition :- These are food additives that duplicate the effect of sugar with le
intake when compared to sugar. Since they are not present naturally they ar
called artificial sugar.
Two types:- One type is called high intensity sweeteners. They have the sa
sweetness profile as sucrose (common table sugar), like saccharin. The oth
different structure from that of sucrose and has a sweetness profile much higsucrose. Examples include Aspartame or sucralose.
Glucose Tolerance Test:- Starve the mice for 6hrours during the light period
mice glucose solution that is calculated according to their body weight. Then
glucose is measured at different time intervals.
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INTRODUCTION
Non-Caloric Artificial Sweeteners (NAS) are very popular because of certain
over normal sugar:-
Low caloric intake
Reduced costs
But the supporting scientific data is not consistent with the perceived health
It is established that humans cannot digest the NAC. Hence they are metabo
gut microbiota.
Diet changes the gut microbiota.
The paper studies the changes in the gut microbiota and links the changes t
effect on human body i.e. glucose intolerance.
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TESTS AND RESULTS Hypothesis:- NAS exacerbates glucose intolerance.
Commercial formulation of saccharin, sucralose and aspartame
was added to drinking water of 10week old lean/healthy mice.
For control, another set of mice were fed water, glucose and
sucrose.
Later saccharin was only studied. Mice were now fed high fat
diet (60% kcal from fat) along with commercial saccharin
supplemented water. Pure glucose supplemented water was
used as control.
For further studies even pure saccharin was administered,keeping pure glucose as control.
Result:- As expected the mice that were fed NAS showed high
level of glucose intolerance, especially with saccharin on the
11thweek itself.
For mice that were fed HFD, glucose intolerance was seen as
early as 5 weeks after the HFD regiment had started.
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Hypothesis:- Gut microbiota mediates NAS-induced glucose
intolerance
The mice of lean and obese state were treated with gram negative
targeting broad spectrum antibiotics namely ciprofloxacin and
metronidazole while maintaining them on their regular diet andsweetener supplement.
Another set of mice were treated similarly with gram positive
targeting broad spectrum antibiotic vancomycin.
Results:- The differences in glucose intolerance between the control
group and the group receiving NAS was abolished after 4weeks.
To further confirm the role of microbiota, fecal transplantation was
performed by transferring the microbiota configuration from mice in
one set to another set of germ free mice.
Result:- The recipient mice which were previously were healthy now
had induced glucose intolerance.
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Hypothesis:- NAS mediate distinct functional alterations to the microbiota
Fecal microbiota was analyzed for the various mouse groups. Analysis is done by sequencing the
gene.
Result:- The microbiota of saccharin consuming mice displayed considerable dysbiosis with more
(operational taxonomic units) significantly altered.
The genus Bacteroides belonging to Clostridiales order had the maximum increase in taxa. Other
order were the majority of under represented taxa along with Lactobaccilus reuteri. This result wa
mice that were receiving fecal transplantation.
Further analysis was carried to determine the change in metabolic pathways. In saccharin consum
degradation pathway increased in which glycans are fermented into short chain fatty acid. SFAs aprecursor and/or signals for de novo synthesis of glucose and lipids in the host. This pathway mar
harvest and has been related to obesity in mice and humans.
Further confirmation was provided by analyzing the levels of SFAs propionate and acetate in stoo
were very high in mice that drank water supplemented with NAS, when compared to control.
The search to find the species of bacteria responsible for increase in glycan degradation pathway
species in which two belonged to Bacterioidesgenus.
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Hypothesis :- NAS directly modulate the microbiota to induce glucose intolerance
Fecal matter from naive mice was grown in strict anaerobic conditions in presence of s
For control the fecal matter was grown in control media. After 9 days of incubation, the
administered by gavage to germ free mice. Later the microbiota composition and GTT
Result:- The mice that were fed the test culture had significantly higher glucose intolera
compared to control. The microbiota of the mice that were fed the test culture had over
members of Bacteroides genus and under-representation of several other Clostridiales
As expected glycan degradation pathway was highly enriched in both sets along sphin
Glucose transport pathway was under represented
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Hypothesis:- NAS in humans associate with impaired glucose tolerance
Study was conducted to see the effect of NAS on humans. 381 non-
diabetic people who consumed NAS for a long term were studied. A
significant positive correlation between NAS consumption and several
metabolic syndrome related clinical parameters like, Increased weight and waist to hip ratio
Higher fasting blood glucose
Glycosylated hemoglobin
GTT
Elevated serum alanine aminotransferase
A group of 7 volunteers who normally dont consume NAS were given NAS
or NAS containing food for 1 week. During the test from day 2 to day 7 thevolunteers were given commercial saccharin as three divided doses
equivalent to 120mg. Their blood glucose was monitored and GTT was
done frequently to determine the effect of NAS on glucose tolerance.
Result :- 4 out of the 7 people developed significantly poorer response on
day 5-7 after NAS consumption when compared to their individual
responses from day 1-4. Other 3 people had no changes in their response.
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The microbiomes was tested for both the groups.
There was significant change in the microbiome of
people who responded to the test.
To further confirm that NAS induced dysbiosis has a
role in induced glucose intolerance, stool from day 1and day 7 from two people who responded to the
test and from two people who didnt respond was
transferred to normal chow feed germ free mice.
Result:- The glucose intolerance induced by postNAS exposure transfer was much higher than day 1
transfer, for the same individual who responded to
the test. On the other hand there was no significant
change in glucose tolerance for mice that were fed
stool of individuals who didnt respond to the test.
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DISCUSSION
NAS consumption enhances the risk of glucose intolerance in both humans and
these adverse metabolic effects are mediated by modulation of the composition microbiota.
Elaborate inter-species microbial cooperation may functionally orchestrate the g
Metagenomes of saccharin consuming mice are enriched with multiple additiona
previously associated with diabetes mellitus or obesity in mice and humans, incl
sphingolipid mechanism and lipid biosynthesis.
The increase in NAS consumption coincides with the dramatic increase in obesiNAS have directly contributed to the enhance the disease that they were suppos
A better strategy would be to develop nutritional intake tailored for the individual
mind the personalized differences in the composition and function of the gut mic
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REFERENCE
Artificial sweeteners induce glucose intolerance by altering the gut microbiota-
Jotham Suez, Tal Korem, David Zeevi, Gili Zilberman-Schapira, Christoph A. Th
Ori Maza, Niv Zmora, Shlomit Gilad, Adina Weinberger, Yael Kuperman, A
Harmelin, Ilana Kolodkin-Gal, Zamir Halpern, Eran Segal & Eran Elinav-
Nature doi:10.1038/nature13793