Ten-Week Sucralose Consumption Induces Gut Dysbiosis and Altered Glucose and Insulin Levels in Healthy Young Adults

Abstract

Sucralose consumption alters microbiome and carbohydrate metabolism in mouse models. However, there are no conclusive studies in humans. Our goals were to examine the effect of sucralose consumption on the intestinal abundance of bacterial species belonging to Actinobacteria, Bacteroidetes, and Firmicutes and explore potential associations between microbiome profiles and glucose and insulin blood levels in healthy young adults. In this open-label clinical trial, volunteers randomly drank water, as a control (n = 20), or 48 mg sucralose (n = 20), every day for ten weeks. At the beginning and the end of the study, participants were subjected to an oral glucose tolerance test (OGTT) to measure serum glucose and insulin every 15 min for 3 h and provided fecal samples to assess gut microbiota using a quantitative polymerase chain reaction. Sucralose intake altered the abundance of Firmicutes without affecting Actinobacteria or Bacteroidetes. Two-way ANOVA revealed that volunteers drinking sucralose for ten weeks showed a 3-fold increase in Blautia coccoides and a 0.66-fold decrease in Lactobacillus acidophilus compared to the controls. Sucralose consumption increased serum insulin and the area under the glucose curve compared to water. Long-term sucralose ingestion induces gut dysbiosis associated with altered insulin and glucose levels during an OGTT.

Personalized microbiome-driven effects of non-nutritive sweeteners on human glucose tolerance

“…However, if such formulation distinction is true, NNS impacts should be compared in future controlled trials between consumers of carbohydrate-rich and carbohydrate-restrictive diets for their potential differential effects on human metabolic physiology. Of note, longer exposure periods (4-10 weeks) to pure NNS were suggested by some studies to negatively impact metabolic health even in the absence of a carbohydrate additive (Bueno-Herna ´ndez et al, 2020;Higgins and Mattes, 2019;Lertrit et al, 2018;Me ´ndez-Garcı ´a et al, 2022). As such, a longer exposure period than the one utilized in our study may be required to fully assess the potential health ramifications mediated by the altered microbiome upon consumption of different NNS.…”

“…Although some randomized-controlled trials (RCTs) report improvement in metabolic markers in subjects supplemented with NNS (Blackburn et al, 1997;Ebbeling et al, 2020;Katan et al, 2016;Masic et al, 2017;Miller and Perez, 2014;Tate et al, 2012), other RCTs report neither a detrimental nor a beneficial effect (Ahmad et al, 2020a;Thomson et al, 2019) and do not support the intended benefits of this approach (Azad et al, 2017;Lohner et al, 2020;Toews et al, 2019). Furthermore, some cohort studies (Azad et al, 2017(Azad et al, , 2020Romo-Romo et al, 2016;Swithers, 2013) and RCTs (Bueno-Herna ´ndez et al, 2020;Dalenberg et al, 2020;Lertrit et al, 2018;Me ´ndez-Garcı ´a et al, 2022;Romo-Romo et al, 2018) counterintuitively suggest that NNS may even contribute to the obesity and diabetes pandemic in some contexts. As many of the studies associating NNS with negative impacts on human health are observational, it is often difficult to interpret their findings due to reverse causality (i.e., whether NNS cause weight gain and hyperglycemia, or alternatively whether individuals with these conditions consume NNS).…”

“…Furthermore, an NNS-modulated microbiome is sufficient to promote glucose intolerance in germ-free (GF) mice (Nettleton et al, 2020;Suez et al, 2014), providing a possible causal link between NNS, microbiome, and metabolic health of the host. Although a small pilot study in humans suggested that the microbiome may constitute a potential determinant of a negative effect of saccharin on glycemic response in some individuals (Suez et al, 2014), there is a dearth of evidence on the effects of NNS on the human microbiome, and the few available studies are inconclusive, with some suggesting an effect (Frankenfeld et al, 2015;Laforest-Lapointe et al, 2021;Me ´ndez-Garcı ´a et al, 2022), as opposed to others (Ahmad et al, 2020b;Serrano et al, 2021;Thomson et al, 2019). Notably, most of these studies were limited in their ability to screen and exclude individuals already incorporating NNS into their diets, and their microbiome was profiled using 16S rRNA gene sequencing or qPCR of target microbes, which may lack sufficient resolution to determine functional and species-level effects of NNS on the microbiome.…”

Is a Non-Caloric Sweetener-Free Diet Good to Treat Functional Gastrointestinal Disorder Symptoms? A Randomized Controlled Trial

“…Accumulating evidence from in vitro and in vivo studies indicated an association of sucralose ingestion with a higher amount of commensal strain subpopulations of the gut microbiota. Some of these bacteria are associated with diarrhea, constipation, or both as a consequence of changes in intestinal permeability [ 35 , 36 , 37 , 38 ].…”

Food Additives Associated with Gut Microbiota Alterations in Inflammatory Bowel Disease: Friends or Enemies?

“…Sucralose, known as trichlorogalactosucrose, has a 600–650 times higher sweetness than sugar. In human studies, the intake of sucralose did not modulate the gut microbiome in a short treatment [ 16 , 89 ], while a ten-week consumption in young adults might lead to an increase in Blautia coccoides and a decrease in Lactobacillus acidophilus , with altered insulin and glucose levels in the serum [ 90 ]. However, Uebanso et al, showed the decreased amount of Clostridium IVXa in feces with a dose-dependent manner in animals [ 22 ].…”