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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.
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The Author(s).
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Eect of Arcial Sweeteners on the Gut
Adekunle Sanyaolu1*
, Chuku Okorie2, Abu Fahad Abbasi3, Aleksandra Marinkovic4, Stephanie
Prakash4, Risha Padar4, Priyank Desai5 and Zaheeda Hosein6
            
and one of the major roles of this system is to break down sugars. Recent studies have
             
           
 
            
             
   
   
                
 
     
            
 
    
taken with caution.
        
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
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
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The Author(s).
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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.
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
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The Author(s).
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Table 1:in vitro
Type of Sweetener Sweetener Name Biological Eect
 Saccharin Escherichia coli (E. coli
Proteus vulgaris by
Decrease Lactobacillus and E. coli 5].
Bacteroides and reduced Firmicutes 5].
Sucralose E. coli strains which are
Firmicutes 10].
Stevia Bidobacteria and
Lactobacilli and decrease the growth of E. coli 2].
 Firmicutes to Bacteroidetes
 FaecalibacteriumAnareostipes, and
Erysipelatoclostridium 11].
genus Parabacteroide 11].
Polyols   Bidobacteria
EnterobacteriaceaeLactobacilli 8].
 9].
Xylitol Decrease Bacteroides8].
metabolic activity of the intestinal microbiota and/
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The Author(s).
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have in vitro, in animal, and human studies.
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
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.
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).
 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.
1.          
2.         
 
3. -
4. 
5.      
6.       -
7. -
8. 
9. 
            
10. -
11. -
12. 
13. 
altering the gut microbiota. 
14. 
15.      
 
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Non-nutritive artificial sweeteners (NNSs) may have the ability to change the gut microbiota, which could potentially alter glucose metabolism. This study aimed to determine the effect of sucralose and aspartame consumption on gut microbiota composition using realistic doses of NNSs. Seventeen healthy participants between the ages of 18 and 45 years who had a body mass index (BMI) of 20–25 were selected. They undertook two 14-day treatment periods separated by a four-week washout period. The sweeteners consumed by each participant consisted of a standardized dose of 14% (0.425 g) of the acceptable daily intake (ADI) for aspartame and 20% (0.136 g) of the ADI for sucralose. Faecal samples collected before and after treatments were analysed for microbiome and short-chain fatty acids (SCFAs). There were no differences in the median relative proportions of the most abundant bacterial taxa (family and genus) before and after treatments with both NNSs. The microbiota community structure also did not show any obvious differences. There were no differences in faecal SCFAs following the consumption of the NNSs. These findings suggest that daily repeated consumption of pure aspartame or sucralose in doses reflective of typical high consumption have minimal effect on gut microbiota composition or SCFA production.
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High consumption of fructose and high-fructose corn syrup is related to the development of obesity-associated metabolic diseases, which have become the most relevant diet-induced diseases. However, the influences of a high-fructose diet on gut microbiota are still largely unknown. We therefore examined the effect of short-term high-fructose consumption on the human intestinal microbiota. Twelve healthy adult women were enrolled in a pilot intervention study. All study participants consecutively followed four different diets, first a low fructose diet (< 10 g/day fructose), then a fruit-rich diet (100 g/day fructose) followed by a low fructose diet (10 g/day fructose) and at last a high-fructose syrup (HFS) supplemented diet (100 g/day fructose). Fecal microbiota was analyzed by 16S rRNA sequencing. A high-fructose fruit diet significantly shifted the human gut microbiota by increasing the abundance of the phylum Firmicutes, in which beneficial butyrate producing bacteria such as Faecalibacterium, Anareostipes and Erysipelatoclostridium were elevated, and decreasing the abundance of the phylum Bacteroidetes including the genus Parabacteroides. An HFS diet induced substantial differences in microbiota composition compared to the fruit-rich diet leading to a lower Firmicutes and a higher Bacteroidetes abundance as well as reduced abundance of the genus Ruminococcus. Compared to a low-fructose diet we observed a decrease of Faecalibacterium and Erysipelatoclostridium after the HFS diet. Abundance of Bacteroidetes positively correlated with plasma cholesterol and LDL level, whereas abundance of Firmicutes was negatively correlated. Different formulations of high-fructose diets induce distinct alterations in gut microbiota composition. High-fructose intake by HFS causes a reduction of beneficial butyrate producing bacteria and a gut microbiota profile that may affect unfavorably host lipid metabolism whereas high consumption of fructose from fruit seems to modulate the composition of the gut microbiota in a beneficial way supporting digestive health and counteracting harmful effects of excessive fructose.
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Intense sweeteners (IS) are often marketed as a healthier alternative to sugars, with the potential to aid in combating the worldwide rise of diabetes and obesity. However, their use has been counterintuitively associated with impaired glucose homeostasis, weight gain and altered gut microbiota. The nature of these associations, and the mechanisms responsible, are yet to be fully elucidated. Differences in their interaction with taste receptors may be a potential explanatory factor. Like sugars, IS stimulate sweet taste receptors, but due to their diverse structures, some are also able to stimulate bitter taste receptors. These receptors are expressed in the oral cavity and extra-orally, including throughout the gastrointestinal tract. They are involved in the modulation of appetite, glucose homeostasis and gut motility. Therefore, taste genotypes resulting in functional receptor changes and altered receptor expression levels may be associated with metabolic conditions. IS and taste receptors may both interact with the gastrointestinal microbiome, and their interactions may potentially explain the relationship between IS use, obesity and metabolic outcomes. While these elements are often studied in isolation, the potential interactions remain unexplored. Here, the current evidence of the relationship between IS use, obesity and metabolic outcomes is presented, and the potential roles for interactions with taste receptors and the gastrointestinal microbiota in modulating these relationships are explored.
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Purpose of Review The supplementation of dietary additives into processed foods has exponentially increased in the past few decades. Similarly, the incidence rates of various diseases, including metabolic syndrome, gut dysbiosis, and hepatocarcinogenesis, have been elevating. Current research reveals that there is a positive association between food additives and these pathophysiological diseases. This review highlights the research published within the past 5 years that elucidate and update the effects of dietary supplements on liver and intestinal health. Recent Findings Some of the key findings include: enterocyte dysfunction of fructose clearance causes non-alcoholic fatty liver disease (NAFLD); non-caloric sweeteners are hepatotoxic; dietary emulsifiers instigate gut dysbiosis and hepatocarcinogenesis; and certain prebiotics can induce cholestatic hepatocellular carcinoma (HCC) in gut dysbiotic mice. Overall, multiple reports suggest that the administration of purified, dietary supplements could cause functional damage to both the liver and gut. Summary The extraction of bioactive components from natural resources was considered a brilliant method to modulate human health. However, current research highlights that such purified components may negatively affect individuals with microbiotal dysbiosis, resulting in a deeper break of the symbiotic relationship between the host and gut microbiota, which can lead to repercussions on gut and liver health. Therefore, ingestion of these dietary additives should not go without some caution!
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The consumption of sugar-free foods is growing because of their low-calorie content and the health concerns about products with high sugar content. Sweeteners that are frequently several hundred thousand times sweeter than sucrose are being consumed as sugar substitutes. Although nonnutritive sweeteners (NNSs) are considered safe and well tolerated, their effects on glucose intolerance, the activation of sweet taste receptors, and alterations to the composition of the intestinal microbiota are controversial. This review critically discusses the evidence supporting the effects of NNSs, both synthetic sweeteners (acesulfame K, aspartame, cyclamate, saccharin, neotame, advantame, and sucralose) and natural sweeteners (NSs; thaumatin, steviol glucosides, monellin, neohesperidin dihydrochalcone, and glycyrrhizin) and nutritive sweeteners (polyols or sugar alcohols) on the composition of microbiota in the human gut. So far, only saccharin and sucralose (NNSs) and stevia (NS) change the composition of the gut microbiota. By definition, a prebiotic is a nondigestible food ingredient, but some polyols can be absorbed, at least partially, in the small intestine by passive diffusion: however, a number of them, such as isomaltose, maltitol, lactitol, and xylitol, can reach the large bowel and increase the numbers of bifidobacteria in humans. Further research on the effects of sweeteners on the composition of the human gut microbiome is necessary. Adv Nutr 2019;10:S31-S48.
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Over a century ago, Artificial Sweeteners (AS) were developed as food additives to provide sweetness without the associated high caloric content of sugar. The United States Food and Drug Administration (FDA) have approved five artificial sweeteners: aspartame, saccharin, acesulfame potassium, neotame and sucralose. These sweeteners have also been deemed safe for people with diabetes and are used to reduce both caloric and carbohydrate intake. However, despite the widespread consumption of artificial sweeteners by lean, overweight and obese individuals alike, obesity and diabetes continue to dramatically rise. This review examines the relationship between artificial sweeteners and diabetes and the need for continued investigation into the consumption of artificial sweeteners.
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Non-nutritive sweeteners (NNSs) are widely used in various food products and soft drinks. There is growing evidence that NNSs contribute to metabolic dysfunction and can affect body weight, glucose tolerance, appetite, and taste sensitivity. Several NNSs have also been shown to have major impacts on bacterial growth both in vitro and in vivo. Here we studied the effects of various NNSs on the growth of the intestinal bacterium, E. coli, as well as the gut bacterial phyla Bacteroidetes and Firmicutes, the balance between which is associated with gut health. We found that the synthetic sweeteners acesulfame potassium, saccharin and sucralose all exerted strong bacteriostatic effects. We found that rebaudioside A, the active ingredient in the natural NNS stevia, also had similar bacteriostatic properties, and the bacteriostatic effects of NNSs varied among different Escherichia coli strains. In mice fed a chow diet, sucralose increased Firmicutes, and we observed a synergistic effect on Firmicutes when sucralose was provided in the context of a high-fat diet. In summary, our data show that NNSs have direct bacteriostatic effects and can change the intestinal microbiota in vivo.
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Polyols are sugar alcohols found in certain fruits, vegetables, and sugar-free sweeteners. They make up a component of the diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols, which is gaining popularity in the treatment of patients with irritable bowel syndrome (IBS). We conducted a systematic review to evaluate the effects of polyols on the gastrointestinal tract in healthy men and women and in patients with IBS. Utilizing PubMed, Ovid, and Embase databases, we conducted a search on individual polyols and each of these terms: fermentation, absorption, motility, permeability, and gastrointestinal symptoms. Standard protocols for a systematic review were followed. We found a total of 1823 eligible articles, 79 of which were included in the review. Overall, available work has shown that polyol malabsorption generally occurs in a dose-dependent fashion in healthy individuals, and malabsorption increases when polyols are ingested in combination. However, studies in patients with IBS have shown conflicting results pertaining to polyol malabsorption. Polyol ingestion can lead to intestinal dysmotility in patients with IBS. Regarding the microbiome, moderate doses of polyols have been shown to shift the microbiome toward an increase in bifidobacteria in healthy individuals and may therefore be beneficial as prebiotics. However, data are limited regarding polyols and the microbiome in patients with IBS. Polyols can induce dose-dependent symptoms of flatulence, abdominal discomfort, and laxative effects when consumed by both healthy volunteers and patients with IBS. Further research is needed to better understand the effects of specific polyols on gastrointestinal function, sensation, and the microbiome in health and gastrointestinal disorders such as IBS.
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Background/aims: Artificial sweeteners (AS) are ubiquitous in food and beverage products, yet little is known about their effects on the gastrointestinal (GI) tract, and whether they play a role in the development of GI symptoms, especially in patients with irritable bowel syndrome. Methods: Utilizing the PebMed and Embase databases, we conducted a search for articles on individual AS and each of these terms: fermentation, absorption, and GI tract. Standard protocols for a systematic review were followed. At the end of our search, we found a total of 617 eligible papers, 26 of which were included. Results: Overall there is limited medical literature available on this topic. The 2 main areas on which there is data to suggest that AS affect the GI tract include motility and the gut microbiome, though human data is lacking and most of the currently available data is derived from in vivo studies. The effect on motility is mainly indirect via increased incretin secretion, though the clinical relevance of this finding is unknown as the downstream effect on motility was not studied. The specific effects of AS on the microbiome have been conflicting and the available studies have been heterogeneous in terms of the population studied and both the AS and doses evaluated. Conclusions: Further research is needed to assess whether AS could be a potential cause of GI symptoms. This is especially pertinent in patients with irritable bowel syndrome, a population in whom dietary interventions are routinely utilized as a management strategy.
Recent results of randomized trials testing the efficacy of xylitol in caries prevention have been conflicting. This narrative review reveals the sources of discrepancy. The following databases were searched for the terms "xylitol" or "artificial sweeteners" restricted to the English language: PubMed, Web of Science, Evidenced-Based Medicine, Scopus, and the Cochrane database. In a separate search, the terms "dental caries" or "cariogenicity" or "glucosyltransferase" or "low glycemic" or "low insulinemic" or "dysbiosis" or "gut microbiome" were used and then combined. In section I, findings regarding the role of xylitol in dental caries prevention, the appropriateness of research methods, and the causes for potential biases are summarized. In section II, the systemic effects of xylitol on gut microbiota as well as low-glycemic/insulinogenic systemic effects are evaluated and summarized. The substitution of a carbonyl group with an alcohol radical in xylitol hinders its absorption and slowly releases sugar into the bloodstream. This quality of xylitol is beneficial for diabetic patients to maintain a constant glucose level. Although this quality of xylitol has been proven in in vitro and animal studies, it has yet to be proven in humans. Paradoxically, recent animal studies reported hyperglycemia and intestinal dysbiosis with artificial sweetener consumption. Upon careful inspection of evidence, it was revealed that these reports may be due to misinterpretation of original references or flaws in study methodology. Any systemic benefits of xylitol intake must be weighed in consideration with the well-established adverse gastrointestinal consequences. The contribution of xylitol to gut dysbiosis that may affect systemic immunity warrants further research.