High-intensity sweetener consumption and gut microbiome content and predicted gene function in a cross-sectional study of adults in the United States

Frankenfeld, Cara L.; Sikaroodi, Masoumeh; Lamb, Evan; Shoemaker, Sarah J.; Gillevet, Patrick M.

doi:10.1016/j.annepidem.2015.06.083

Cited by 101 publications

(71 citation statements)

References 51 publications

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“…Recent studies have reported that consuming NCS may disrupt microbiome diversity in both rats and humans 18,[41][42][43][44] and further suggest that this may lead to glucose intolerance. Similarly, another cross-sectional study reported that consuming NCS has no effect on microbiome abundance and gene function however consuming NCS alters the microbiome diversity 45 . Further studies have also shown that alteration of microbial diversity may lead to metabolic changes 46,47 .…”

Section: Discussionmentioning

confidence: 98%

Rebaudioside affords hepatoprotection ameliorating sugar sweetened beverage- induced nonalcoholic steatohepatitis

Xi¹,

Bhattacharjee²,

Salazar-González³

et al. 2020

Sci Rep

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Sugar-sweetened beverage consumption is a known independent risk factor for nonalcoholic steatohepatitis (NASH). Non-caloric sweeteners (NCS) are food additives providing sweetness without calories and are considered safe and/or not metabolized by the liver. The potential role of newer NCS in the regulation of NASH, however, remain unknown. Our study aimed to determine the impact of newer NCS including Rebaudioside A and sucralose on NASH using high fat diet induced obesity mouse model by substituting fructose and sucrose with NCS in the drinking water. We characterized the phenotype of NCS-treated obesity and investigated the alterations of hepatic function and underlying mechanisms. We found that NCS have no impact on weight gain and energy balance in high fat diet induced obesity. However, in comparison to fructose and sucrose, Rebaudioside A significantly improved liver enzymes, hepatic steatosis and hepatic fibrosis. Additionally, Rebaudioside A improved endoplasmic reticulum (ER) stress related gene expressions, fasting glucose levels, insulin sensitivity and restored pancreatic islet cell mass, neuronal innervation and microbiome composition. We concluded that Rebaudioside A significantly ameliorated murine NASH, while the underlying mechanisms requires further investigation. Current treatment strategies for nonalcoholic steatohepatitis (NASH) have focused on lifestyle management of modifiable risk factors, through a combination of diet and exercise 1-3. Potential therapeutic targets for NASH intersect with the complex pathogenesis of NASH including hepatic steatosis from the imbalance of lipogenesis and free fatty acid (FFA) promoting inflammatory response and fibrosis progression 4,5. However, despite pharmaceutical agents currently in advanced stages of clinical testing 6-8 , NASH is on track predicted to become the main reason for liver transplant in the very near future 9. Therefore, it is essential to continue to explore novel NASH therapies. Sugar sweetened beverages are now well acknowledged to have severe consequences on human health. Consequently, non-caloric sweeteners (NCS) such as aspartame, sucralose, saccharin, and Rebaudioside A have increased in popularity and usage. However, there is a limited evidence for the benefits of frequent consumption of NCS sugar substitutes. This is especially true for the most recent addition Rebaudioside A, that is an extract of the stevia leaf that provides sweetness without calories 10. Interestingly, recent literature has reported that Rebaudioside A may in fact play a role in glucose metabolism and has even been reported to improve post-prandial glucose-insulin index 11 , and its consumption may result in weight loss in mice fed a high fat diet 12. These observations suggest a potential role for Rebaudioside A on glucose metabolism in general, and on liver function and NASH in particular. The well-known interactions between human health, diet and intestinal microbiota are based on the involvement of the microbiome in metabolism and immunity, which also par...

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Section: Discussionmentioning

confidence: 98%

Rebaudioside affords hepatoprotection ameliorating sugar sweetened beverage- induced nonalcoholic steatohepatitis

Xi¹,

Bhattacharjee²,

Salazar-González³

et al. 2020

Sci Rep

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“…In a recently published study, Frankenfeld et al observed significant differences in the human gut microbiota when comparing consumption of artificial sweeteners to that of a regular diet, explicitly demonstrating a difference in the bacterial makeup in patients with an increased ASP and acesulfame-K intake after only a 4-day trial (Frankenfeld et al 2015). Although the trials were aiming to study acute changes in high-dose settings, the results raise the question of the long-term effects of artificial sweeteners.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of the gut enzyme intestinal alkaline phosphatase may explain how aspartame promotes glucose intolerance and obesity in mice

Gul

Hamilton

Munoz

et al. 2017

Appl. Physiol. Nutr. Metab.

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Diet soda consumption has not been associated with tangible weight loss. Aspartame (ASP) commonly substitutes sugar and one of its breakdown products is phenylalanine (PHE), a known inhibitor of intestinal alkaline phosphatase (IAP), a gut enzyme shown to prevent metabolic syndrome in mice. We hypothesized that ASP consumption might contribute to the development of metabolic syndrome based on PHE’s inhibition of endogenous IAP. The design of the study was such that for the in vitro model, IAP was added to diet and regular soda, and IAP activity was measured. For the acute model, a closed bowel loop was created in mice. ASP or water was instilled into it and IAP activity was measured. For the chronic model, mice were fed chow or high-fat diet (HFD) with/without ASP in the drinking water for 18 weeks. The results were that for the in vitro study, IAP activity was lower (p < 0.05) in solutions containing ASP compared with controls. For the acute model, endogenous IAP activity was reduced by 50% in the ASP group compared with controls (0.2 ± 0.03 vs 0.4 ± 0.24) (p = 0.02). For the chronic model, mice in the HFD + ASP group gained more weight compared with the HFD + water group (48.1 ± 1.6 vs 42.4 ± 3.1, p = 0.0001). Significant difference in glucose intolerance between the HFD ± ASP groups (53 913 ± 4000.58 (mg·min)/dL vs 42 003.75 ± 5331.61 (mg·min)/dL, respectively, p = 0.02). Fasting glucose and serum tumor necrosis factor-alpha levels were significantly higher in the HFD + ASP group (1.23- and 0.87-fold increases, respectively, p = 0.006 and p = 0.01). In conclusion, endogenous IAP’s protective effects in regard to the metabolic syndrome may be inhibited by PHE, a metabolite of ASP, perhaps explaining the lack of expected weight loss and metabolic improvements associated with diet drinks.

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“…Intestinal alkaline phosphatase is a protective, anti-inflammatory enzyme; its inhibition has been associated with increased intestinal inflammation, dysbiosis, and bacterial translocation resulting in systemic inflammation [36]. In human studies evaluating the effects of aspartame intake in healthy adults, aspartame consumers demonstrated a difference in overall bacterial diversity, although no differences in bacterial abundance or gene diversity were observed [37]. Human immunodeficiency virus infection is also known to alter the intestinal microbiota [38], and these alterations may also contribute to immune activation and inflammation in HIV.…”

Section: Discussionmentioning

confidence: 99%

Aspartame Intake Relates to Coronary Plaque Burden and Inflammatory Indices in Human Immunodeficiency Virus

Hall

Sánchez-Lorenzo

Hubbard

et al. 2017

Open Forum Infectious Diseases

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Background.Dietary sweeteners may contribute to metabolic dysregulation and cardiovascular disease (CVD), but this has not been assessed in human immunodeficiency virus (HIV).Methods.One hundred twenty-four HIV-infected and 56 non-HIV-infected participants, without history of known coronary artery disease were included. Dietary intake was assessed using a 4-day food record. Coronary plaque was determined using cardiac computed tomography angiography.Results.Human immunodeficiency virus-infected participants had significantly greater intake of dietary sweeteners, including total sugar (P = .03) and added sugar (P = .009); intake of aspartame (artificial sweetener) was greater among aspartame consumers with HIV versus non-HIV consumers (P = .03). Among HIV-infected participants, aspartame intake was significantly associated with coronary plaque (P = .002) and noncalcified plaque (P = .007) segments, as well as markers of inflammation/immune activation (monocyte chemoattractant protein 1 and lipoprotein-associated phospholipase A2), which may contribute to increased atherogenesis. In multivariable regression modeling, aspartame remained an independent predictor of plaque in HIV. In contrast, among non-HIV-infected participants, no sweetener type was shown to relate to plaque characteristics.Conclusions.We demonstrate increased intake of dietary sweeteners and a potential novel association between aspartame intake, plaque burden, and inflammation in HIV. Our data suggest that aspartame may contribute to CVD risk in HIV. Further studies should address potential mechanisms by which aspartame may contribute to increased plaque burden and cardiovascular benefits of dietary strategies targeting aspartame intake in HIV.

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High-intensity sweetener consumption and gut microbiome content and predicted gene function in a cross-sectional study of adults in the United States

Cited by 101 publications

References 51 publications

Rebaudioside affords hepatoprotection ameliorating sugar sweetened beverage- induced nonalcoholic steatohepatitis

Rebaudioside affords hepatoprotection ameliorating sugar sweetened beverage- induced nonalcoholic steatohepatitis

Inhibition of the gut enzyme intestinal alkaline phosphatase may explain how aspartame promotes glucose intolerance and obesity in mice

Aspartame Intake Relates to Coronary Plaque Burden and Inflammatory Indices in Human Immunodeficiency Virus

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