Acesulfame potassium induces dysbiosis and intestinal injury with enhanced lymphocyte migration to intestinal mucosa

Abstract

Background and Aim The artificial sweetener acesulfame potassium (ACK) is officially approved as safe for intake and has been used in processed foods. However, ACKs have been reported to induce metabolic syndrome, along with alteration of the gut microbiota in mice. In recent years, studies have suggested that this artificial sweetener promotes myeloperoxidase reactivity in Crohn's disease‐like ileitis. We aimed to investigate the effect of ACK on the intestinal mucosa and gut microbiota of normal mice. Methods Acesulfame potassium was administered to C57BL/6J mice (8 weeks old) via free drinking. Intestinal damage was evaluated histologically, and messenger RNA (mRNA) levels of TNF‐α, IFN‐γ, IL1‐β, MAdCAM‐1, GLP1R, and GLP2R were determined with quantitative reverse transcription polymerase chain reaction (qRT‐PCR). Immunohistochemistry was performed to examine the expression of MAdCAM‐1 in the small intestine. The composition of gut microbiota was assessed using high‐throughput sequencing. We performed intravital microscopic observation to examine if ACK altered lymphocyte migration to the intestinal microvessels. Results Acesulfame potassium increased the expression of proinflammatory cytokines, decreased the expression of GLP‐1R and GLP‐2R, and induced small intestinal injury with an increase in intestinal permeability, and ACK treatment induced microbial changes, but the transfer of feces alone from ACK mice did not reproduce intestinal damage in recipient mice. ACK treatment significantly increased the migration of lymphocytes to intestinal microvessels. Conclusion Acesulfame potassium induces dysbiosis and intestinal injury with enhanced lymphocyte migration to intestinal mucosa. Massive use of non‐caloric artificial sweeteners may not be as safe as we think.

Food Additives, a Key Environmental Factor in the Development of IBD through Gut Dysbiosis

“…These microbial changes are associated with modification of the pathophysiology of the intestinal barrier. Increased permeability was observed in various mice model studies after consumption of acesulfame potassium [72] or sucralose [75,77,87]. Induced intestinal injury with enhanced lymphocyte migration to intestinal mucosa was observed in mice consuming acesulfame potassium [72].…”

“…Figure 1 illustrates the main results of preclinical studies assessing the effects of the exposure of some artificial sweeteners (aspartame, saccharin, sucralose, and acesulfame potassium) on gut microbiota. Recent mice model studies demonstrated a reduction in gut bacterial diversity with an alteration of bacterial communities leading to dysbiosis after consumption of acesulfame potassium [72,73], sucralose [73][74][75][76][77], sucrose [76], or Splenda ® [78] as well as aspartame [79] and neotame [80]. Indeed, the consumption of sucralose, but not acesulfame potassium, can reduce the relative amount of Clostridium cluster XIVa [73].…”

“…Indeed, the consumption of sucralose, but not acesulfame potassium, can reduce the relative amount of Clostridium cluster XIVa [73]. Other studies assessed an increase in Bacteroides, significant changes in Anaerostipes and Sutterella abundances, and a decrease in abundance of Lactobacillus [81], Clostridium [72,81], Lachnospiraceae [72], Ruminoccocaceae [72] in acesulfame potassium-treated male mice.…”

“…Increased permeability was observed in various mice model studies after consumption of acesulfame potassium [72] or sucralose [75,77,87]. Induced intestinal injury with enhanced lymphocyte migration to intestinal mucosa was observed in mice consuming acesulfame potassium [72]. Moreover, the expression of glucagon-like peptide (GLP)-1 and 2 receptors was significantly reduced in acesulfame potassium-treated animals.…”

“…Moreover, the expression of glucagon-like peptide (GLP)-1 and 2 receptors was significantly reduced in acesulfame potassium-treated animals. GLP signaling modulates the epithelial barrier function by tightening intercellular junctions [72]. Santos et al studied the effect of acesulfame potassium, sucralose, aspartame, and saccharin in vitro on intestinal barrier functions and found that only saccharin increased permeability [88].…”