Effect of Artificial Sweeteners on the Gut Microbiome

Abstract

The human gut microbiome has at least one thousand different species of bacteria, and one of the major roles of this system is to break down sugars. Recent studies have suggested that alterations to the microbiome by increased sugar or fat intake (i.e., poor dietary practices) may negatively impact its digestive function. In response, artificial and non-nutritive sweeteners (NNS) have been promoted as healthy alternatives as they require lower amounts ingested to achieve the same satiating effects. In this review, a collection of recent studies was surveyed involving artificial sweeteners (AS) and their effect on the gut microbiome, to assess the growing body of evidence of health concerns arising from sugar substitutes in diets. This literature review spanned cellular, animal, and human studies indexed across five major scientific databases. From this review, it was concluded that the use of AS severely alters the function of the gut microbiome. There is also an interesting, albeit still an unexplored individualized element to this effect, which falls in line with current precision medicine initiatives. To this end, numerous ongoing clinical trials have been designed to further explore the effect of AS and its associations with weight gain. In conclusion, although AS was originally designed to alleviate the negative effects of high sugar diets, there is a growing body of evidence that suggests that these chemical agents carry their risks, especially regarding the human gut microbiome, and should therefore be taken with caution.

Full text

Volume 4 | Issue 1
SCIOL
Biomedicine
Copyright: © 2021
The Author(s).
• Page 179 of 183 •
LIBRARY
PEN ACCESS
Eect of Arcial Sweeteners on the Gut
Microbiome
Adekunle Sanyaolu1*
i
D
, Chuku Okorie2, Abu Fahad Abbasi3, Aleksandra Marinkovic4, Stephanie
Prakash4, Risha Padar4, Priyank Desai5 and Zaheeda Hosein6
Abstract
            
and one of the major roles of this system is to break down sugars. Recent studies have
             
           

 
            
             
   
   
                
 

     
            
 
    
taken with caution.
Keywords
        

1Federal Ministry of Health, Abuja, Nigeria
2Union County College, Plainfield Campus, New Jersey, USA
3Loyola University Medical Center, Maywood, Illinois, USA
4Saint James School of Medicine, Anguilla, BWI
5American University of Saint Vincent School of Medicine, Saint Vincent and the Grenadines
6Caribbean Medical University School of Medicine, Curacao

*Correspondence to:
Dr. Adekunle Sanyaolu
Citaon: Sanyaolu A, Okorie
C, Abbasi AF, Marinkovic A,
Prakash S, et al. (2021) Eect
of Arcial Sweeteners on
the Gut Microbiome. SCIOL
Biomed 2021;4:179-183
Accepted: April 06, 2021
Published: April 08, 2021
Introducon
Human beings have clusters of microorganisms that colonize specic sites in the
body. The collecon of bacteria, viruses, and fungi are referred to as the microbiome
[1]. The human gut microbiota contains at least one thousand dierent species of
known bacteria, of which two-thirds are specic to each individual [1]. The role of
gut microbes consists of polysaccharide breakdown, nutrient absorpon, inamma-
tory responses, gut permeability, and bile acid modicaon [1]. Ongoing research
suggests that alteraons to these microorganisms by the use of increased amounts
of sugars and fat in the diet or the use of anbiocs alters the digesve funcon of
the gut microbiome and may contribute to the development of acne, diarrhea, aller-
gies, autoimmune disease, cancer, and metabolic syndrome, which includes weight
gain and insulin resistance [1].
Non-nutrive sweeteners (NNS) are substutes that mimic a high intensity, low
 2631-4053

Volume 4 | Issue 1
SCIOL Biomed 2021;4:179-183
Copyright: © 2021
The Author(s).
PEN ACCESS
 2631-4053 |
• Page 180 of 183 •
caloric sugar. These alternaves are referenced as synthec or natural sweeteners
which are promoted as healthier alternaves. Due to the intense sweet taste, small-
er amounts can be used [2]. Examples of NNS consist of acesulfame potassium, neo-
tame, sucralose, aspartame, monk fruit extract, steviol glycosides, and erythritol to
name a few [3]. These substutes produce a sweeter avor when compared to nutri-
ve sweeteners (NS) such as sucrose, dextrose, and high-fructose corn syrup (HFCS)
[3]. NNS is used in the food and beverage market because of its low cost and low or
zero-calorie counts for weight loss and normalizaon of blood glucose levels [3]. Ste-
via extracts, a natural sweetener, interacts directly with the gut microbiota because
it is not metabolized in the upper gastrointesnal (GI) tract; therefore, it disrupts
the composion and funcon of the microorganisms directly [2]. Also, saccharin and
sucralose, NNS, have been observed in shiing the gut microora [2].
Short-chain fay acids SCFAs are aected by changes in the diet [3]. These fay
acids are the main end-product resulng from the fermentaon of non-digesble
carbohydrates that become accessible to the gut microbiota [3]. They play a role in
glucose metabolism, lipid metabolism, appete regulaon, and the immune system
[3]. Gut microbiota dysbiosis, a microbial imbalance, may iniate an impairment of
glucose metabolism causing a change in number, composion, or quality of the gut
microbiome [3]. This may result from diets rich in saturated fat, rened sugar, and
decreased physical acvity [3]. Hence, this review invesgates how NNS (i.e., saccha-
rin), NS (i.e., HFCS), and low-calorie sweeteners (LCS), such as polyols (i.e., xylitol)
may aect the gut microbiota composion.
Methodology
An electronic literature search was performed using PubMed, Google Scholar, EB-
SCOhost, Mendeley, and MedLine Plus. The search was limited to peer-reviewed ar-
cles published from January 1, 2010, unl January 17, 2021. An arcle was selected
if it included keywords such as arcial sweeteners (AS), non-nutrive sweeteners
(NNS), nutrive sweeteners (NS), polyols gut microbiome, microbiota, and sweeten-
ing agents. Arcles were then reviewed and included based on the applicability to
the topic.
Sweeteners on the gut microbiota
AS are sugar alternaves that impact the gut microbiota, respecvely depicted
in Table 1. In the United States, AS is used as a sugar substute to provide sweet-
ness with the low caloric content of sugar [2,4]. They are widely used in so drinks,
powdered drink mixes, baked goods, canned foods, jams, and many other processed
foods. NNS is low in calories or contains no calories. Saccharin is an NNS that is two
hundred to seven hundred mes sweeter than table sugar and it contains no cal-
ories. It is commonly used in fruit drinks and mixes. Another example of an NNS is
sucralose, which is six hundred mes sweeter than sugar and is used in many baked
goods, beverages, frozen dairy desserts, chewing gum, and gelan. Sucralose is com-
monly used because it is soluble in ethanol, methanol, and water [5]. Also, sucralose
is stable in heat and over a range of pH condions [5].
NS add caloric value and provide energy in the form of carbohydrates. Examples
of NS include agave, fructose, HFCS, and honey [6]. HFCS is manufactured by enzy-
mac processes that lead to paral isomerizaon of glucose and is used in many
processed beverages and foods [7]. Furthermore, polyols are sugar alcohols found in
sugar-free sweeteners, certain fruits, and vegetables [8]. They share a similarity with
NNS in the sense of being heat stable and not altering in a variety of pH condions
[9]. Also, they are used as food addives as an alternave to sucrose because it has
fewer calories [8]. Examples of polyols include erythritol, hydrogenated starch hy-
drolysates, isomalt, lactol, maltol, mannitol, sorbitol, and xylitol [9]. Xylitol is nat-
urally found in dierent fruits, berries, vegetables, oats, and mushrooms, and a small
percentage is also produced by the human body. Xylitol is used in sugar-free candies
and chewing gums [8]. Table 1 shows the dierent biologic eects that sweeteners

Volume 4 | Issue 1
SCIOL Biomed 2021;4:179-183
Copyright: © 2021
The Author(s).
PEN ACCESS
 2631-4053 |
• Page 181 of 183 •
Table 1:in vitro
Type of Sweetener Sweetener Name Biological Eect
 Saccharin ● Escherichia coli (E. coli
10].
● 
5].
● Proteus vulgaris by
5].
● 5].
● 
5].
● 5].
● 5].
● Decrease Lactobacillus and E. coli 5].
● Bacteroides and reduced Firmicutes 5].
● 
5].
Sucralose ● E. coli strains which are
10].
● 
Firmicutes 10].
● 

10].
Stevia ● Bidobacteria and
Lactobacilli and decrease the growth of E. coli 2].
Nutritive

 ● Firmicutes to Bacteroidetes
7].
● Firmicutes
11].
●  FaecalibacteriumAnareostipes, and
Erysipelatoclostridium 11].
● Bacteroidetes
genus Parabacteroide 11].
Polyols   Bidobacteria

EnterobacteriaceaeLactobacilli 8].
 9].
Xylitol ● Decrease Bacteroides8].
● 

8].
● 
12].
● 
metabolic activity of the intestinal microbiota and/
12].
Note:257-12].

Volume 4 | Issue 1
SCIOL Biomed 2021;4:179-183
Copyright: © 2021
The Author(s).
PEN ACCESS
 2631-4053 |
• Page 182 of 183 •
have in vitro, in animal, and human studies.
Discussion
The human gut contains an abundance of microbiota that keeps digeson normal
and healthy. The microora or microbiome located in the gut helps with a vast array
of funcons from nutrient absorpon to polysaccharide breakdown [1]. With the
increase in diet trends and humans acvely looking for a “low-calorie” alternave to
their favorite foods and beverages, the use of AS is increasing.
The gut has a plethora of bacteria species, NNS selecvely inhibit or enhance the
growth of some bacteria, thus changing the balance of the overall gut microbiota
[10]. Table 1 idenes some of the biological eects that sweeteners such as saccha-
rin, sucralose, stevia, HFCS, lactol, and xylitol have. For example, high consumpon
of fructose and HFCS is related to the development of obesity-associated metabolic
disease [11,12]. Fructose in the colon interacts with the gut microbiota causing dys-
biosis due to an increase in the Firmicutes and Bacteroidetes rao [7].
Sweeteners that are used as sugar alternaves have been shown to have dier-
ent biologic eects. NNS such as saccharin and sucralose shi the populaon of gut
microbiota [9]. A study in mammalian hosts demonstrates that saccharin directly
modies the composion and funcon of the microbiome, thus inducing dysbiosis.
More specically, saccharin causes a ten mes decrease in Candidatus arthromitus,
and twenty mes increase in Bacteroides fragilis and Weissella cibaria [13]. Further-
more, in vitro stool culture with saccharin showed a decrease in Firmicutes and an
increase in Bacteroidetes [13]. Sucralose gut dysbiosis is due to the altered Clostrid-
ium cluster XIVa and Proteobacteria [7]. NNS changes the proporons of intesnal
microbial phyla through a selecve bacteriostac eect. For example, a study found
that E. coli K-12 was more sensive than E. coli HB101 to Ace K and sucralose, while
E. coli HB10 was more sensive to stevia [10].
Stevia also aects the gut microbiota arrangement [9]. In vitro, it was shown that
stevia decreased the growth of E. coli strains and increased the growth of Bidobac-
teria and Lactobacilli. This is due to stevia extracts not metabolizing in the upper GI
tract and directly interacng with colonic microbiota [2]. An in vitro study showed
that xylitol suppresses the growth of S. pneumonia, α- and β-hemolyc streptococci
[14].
Furthermore, xylitol also inhibits the growth of glucose-fermenng microbiotas
due to the suppression of glucosyltransferase [14]. In humans and mice, it was also
found that the fecal microbiome shied from gram-negave to gram-posive bac-
teria [14]. Xylitol also increases osmoc pressure and causes laxaon and diarrhea
[14]. Lactol as a sweetener in low doses is prebioc because it benecially aects
the fecal microbiota. In parcular, lactol increases bidobacteria along with propi-
onic and butyric acid concentraons [9].
It is inferred from the research that the gut microbiome is severely altered with
the use of AS. The implicaons of the degree of alteraon can dier from person to
person. There are currently many clinical trials studying the eect of AS and their
associaon with weight gain and alteraon to the gut microbiota; however, epide-
miological studies in children have shown a posive associaon with weight gain
[15]. The extent of these alteraons can lead to all sorts of metabolic derangements
in humans and needs to be further studied.
Conclusion
AS are widely used in processed products ranging from so drinks and jams to
baked and canned foods. These sugar substutes are two hundred to seven hun-
dred mes sweeter than sugar and contain no calories, making their consumpon
extremely popular. AS is known to directly modify the composion and funcon of
gut microbiomes, which aects natural chemical breakdowns and nutrient absorp-

Volume 4 | Issue 1
SCIOL Biomed 2021;4:179-183
Copyright: © 2021
The Author(s).
PEN ACCESS
 2631-4053 |
• Page 183 of 183 •
on. Ongoing research suggests that the impact of these modicaons alters diges-
ve funcon and may contribute to the development of acne, diarrhea, allergies,
autoimmune disease, cancer, and metabolic syndrome which includes weight gain
and insulin resistance. Impacts vary between individuals; however, epidemiological
studies in children have shown a posive associaon with weight gain. Long-term
eects require further research and invesgaon to isolate which compounds have
the potenal to incite the most changes, whether they be for beer or for worse.
References
1.          

2.         
 
3. -


4. 

5.      

6.       -
ture.
7. -

8. 

9. 
            
S31-S48.
10. -

11. -

12. 

13. 
altering the gut microbiota. 
14. 

15.      
 