NAS induced glucose intolerance

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


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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

NAS induced glucose intolerance

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