Inflammatory bowel disease (IBD) is known as a chronic inflammatory disease that primarily impacts the gastrointestinal (GI) tract and induces immune system disorder [1]. The primary manifestations of IBD consist of two distinct conditions: Crohn's Disease (CD) and ulcerative colitis (UC). The CD has the potential to affect any part of the gastrointestinal tract and exhibits transmural involvement. Colonoscopy findings associated with CD include skip lesions, cobblestoning, ulcerations, and strictures. On the other hand, UC typically occurs exclusively in the colon and affects only the mucosa and submucosa. Classic colonoscopy findings for UC involve pseudopolyps and continuous areas of inflammation [1]. Accumulating evidence suggests that both the incidence and prevalence of IBD are dramatically increasing worldwide [2]. Estimations indicate that around 1.3% in the United States (US) are affected by IBD. In North America, the CD incidence rates vary between 0 and 20.2 per 100,000 individuals per year, while for UC they range from 0 to 19.2 per 100,000 individuals per year. The prevalence rates range from 25.9 to 318.5 cases per 100,000 individuals for CD and from 37.5 to 248.6 cases per 100,000 individuals for UC [3, 4]. In comparison to Western countries, South Korea has a lower prevalence of IBD. However, there is a gradually increasing trend in the incidence rate of the disease in the country. Over the past 10 years in South Korea, the number of patients with IBD has increased by 66.5%, with 68,524 patients reported in 2018 compared to 41,163 patients in 2009 [5]. IBD patients have various symptoms including include weight loss, diarrhea, bleeding, and abdominal pain accompanied by persistent inflammatory responses on the mucosal surface [6]. Inflammation in IBD can be triggered by a variety of factors, including harmful environmental factors, bacterial infections, and external toxic chemicals. This inflammatory response leads to the dysfunction and cell death in normal cells within the affected tissues [7]. The microbiome composition in individuals with IBD is typically different from that of healthy individuals, characterized by variations in specific microbial species or groups and overall community. These changes in the microbiome are considered influential factors in the progression of IBD [8]. Therefore, it is crucial to characterize the risk factors that contribute to the increased incidence of IBD in modern society and explore strategic factors that can reduce IBD symptoms related to inflammation and microbiome.

It’s well known that excessive consumption of added sugar has been linked to various dysfunctions in tissues and organs. It is known to contribute to weight gain, type 2 diabetes, insulin resistance, cardiovascular diseases, non-alcoholic fatty liver disease, and systemic inflammation [9, 10]. Food and Drug Administration highly recommends individuals restrict their consumption of added sugars to no more than 10% of their total daily calorie intake. It highlights the significance of reducing the consumption of added sugars in order to promote general health [11]. In modern society, excessive added sugar consumption has been recognized as one of the associated factors to the increased incidence of IBD and a significant risk factor for the development of IBD [12, 13, 14, 15]. Polysaccharides obtained from many plants, animals, and microorganisms in nature, such as pectin, chitosan, and fructan, have been shown to exert a positive therapeutic effect on IBD [16, 17]. However, Hou et al. [12] found that a high intake of both mono- and di-saccharides was linked to an increased risk of developing CD. Furthermore, natural sweeteners have emerged as popular and safer sweeteners compared to artificial sweeteners, which are chemically synthesized compounds having intensely sweet without calories, in the U.S. market [18]. Unlike artificial sweeteners, natural sweeteners have a more positive track record and are associated with fewer health complications and diseases [18]. They offer a viable substitute for simple sugar, prioritizing the well-being of individuals [18]. Therefore, it is necessary to identify natural sweeteners among the mono-saccharides and di-saccharides, which can be used as alternative sugars and determine their effects on IBD.

This study aims to systematically review 1) current evidence regarding the association between IBD and added sugars, 2) the valid data showing the current research status of natural alternative sweeteners, especially mono-saccharides and di-saccharides, 3) natural alternative sweeteners-mediated various physiological mechanisms contributing to the development/progression of IBD. This comprehensive literature review will provide nutritional knowledge and support individuals with IBD. Hence, this will suggest future research directions of using natural alternative sweeteners as a potential therapeutic reagent in improving IBD.

To review the existing research papers on IBD and its relationship with added sugar or natural alternative sweeteners, electronic databases were utilized through the internet. Google Scholar and PubMed were used as search engines, and the data were extracted in April 2023 and papers published after the year 2000 were included. Using the aforementioned search engines, papers containing the keywords ‘IBD’ or ‘inflammation related to IBD’ in their titles, abstracts, or keywords were initially selected as the primary target. Subsequently, a secondary search was conducted using additional keywords such as‘added sugar’, ‘alternative sweetener’, ‘monosaccharide’, and ‘disaccharide’ to summarize the effects and mechanisms of added sugar and natural alternative sweeteners among the retrieved papers. The following criteria were used to exclude certain papers from the search results: i) Non-peer-reviewed papers such as books or conference proceedings, ii) papers for which the full text was not available, iii) papers written in languages other than English, iv) papers that had redundant or overlapping information regarding the mechanisms studied, v) papers that focused on artificial sweeteners, vi) papers that investigated high-intensity sweeteners. These papers were excluded to ensure the reliability and relevance of the selected literature. A total of 21 papers were used to delineate the link between IBD and added sugar or natural alternative sweeteners, in particular mono-saccharides and di-saccharides. These papers were selected specifically to review the impact of added sugar or alternative sweeteners on IBD.

This narrative review demonstrates the meaningful association between excessive consumption of added sugar and the development and progression of IBD, highlighting the potential of natural functional sweeteners as alternatives having beneficial effects of inflammation, gut microbial composition, protection of the intestinal barrier, and immune modulation, all of which contribute to the potential alleviation of IBD symptoms (Table 1). However, the overall effects of natural alternative sweeteners on IBD are currently limited in human studies, with most of the research conducted at the cellular or animal model level. There is a need for further intervention studies involving IBD patients to establish a more definitive evaluation of their efficacy. In addition, the functional natural sweeteners discussed in this review are not widely used in the food industry. Continued research is necessary to stimulate interest and urge the food industry to develop functional sweetener products specifically designed for IBD patients.

Table 1
Summary of the added sugars on inflammatory bowel disease (IBD)

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This review study provided comprehensive insights on the effects of added sugar, particularly mono-saccharides and di-saccharides on IBD that have been studied so far, highlighting areas that require further investigation and emphasizing the need for systematic analysis. However, it is important to acknowledge certain limitations in the existing evidence, including small sample sizes, short study durations, and a dearth of clinical studies. Therefore, further research is warranted to gain a comprehensive understanding of the long-term effects of natural alternative sweeteners on IBD, encompassing inflammation and the gut microbiome. Future investigations should involve larger cohorts of individuals with IBD and extended assessment periods to summarize the effects of natural alternative sweeteners on IBD more comprehensively. Additionally, the focus of current investigation was primarily on mono-saccharides and di-saccharides among various natural sweeteners including poly-saccharides and oligosaccharides. Therefore, the evaluation of other natural sweeteners' efficacy in IBD is needed in the future. Future research should consider evaluating the efficacy of a broader range of natural sweeteners, including poly-saccharides, and comparing their efficacies with that of mono-saccharides and di-saccharides which were discussed in this study. Overall, the systematic examination of these natural alternatives provides valuable insights into the detrimental effects of excessive added sugar intake in IBD and highlights the need for continued research and development of functional sweeteners that can safely support the well-being of IBD patients.

Utilizing natural alternative sweeteners as functional replacements for detrimental mono-saccharides and di-saccharides can have advantageous effects in the management of IBD (Fig. 2). These sweeteners have been found to have varying effects on reducing inflammation and oxidative stress, regulating macrophage polarization, and improving gut microbiota. However, the current evidence related to functional alternative sweeteners on IBD is limited to cellular and animal studies, and more intervention studies involving IBD patients are needed for a definitive evaluation of their efficacy. Further research should also explore a wider range of natural sweeteners, including poly-saccharides, and compare their effects with mono-saccharides and di-saccharides. Such endeavors will yield more robust evidence and contribute to a deeper comprehension of the potential advantages and limitations of natural alternative sweeteners in the prevention and treatment of IBD.

Fig. 2
Mechanism of added sugars and functional alternative sweeteners in inflammatory bowel disease. The potential mechanisms of action of added sugars and functional alternative sweeteners in the context of inflammatory bowel disease (IBD). The figure highlights the effects of functional alternative sweeteners described in the manuscript on key processes involved in IBD pathogenesis and management. Detailed mechanisms were described in table 1 and 2.

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