Sweeteners and the Gut Microbiome: Effects on Gastrointestinal Cancers
Abstract
:1. Introduction
1.1. Natural and Synthetic Sweeteners
1.2. Metabolization of Sweeteners by Gut Microbiome
1.3. Sweeteners and Gastrointetional Cancers
2. Search Strategy and Selection Criteria
3. Sweeteners and the Gut Microbiome
3.1. Steviol Glycoside
3.2. Glycyrrhizin
3.3. Neohesperidin Dihydrochalcone
3.4. Saccharin
3.5. Sucralose
4. Sweeteners’ Role in Gastrointestinal Cancers
4.1. Apoptosis
4.2. The Nuclear Factor-κB Pathway
4.3. Cellular Cycle Arrest
4.4. Synthetic Sweeteners and GI Cancers
5. Discussion
5.1. Safety of Sweeteners and Challenges in the Field
5.2. Sweeteners’ Role in Cancer Therapy Development
5.3. What about Aspartame?
6. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
NNS | non-nutritive sweeteners |
GI | gastrointestinal |
NHDC | neohesperidin dihydrochalcone |
IL-6 | interleukin 6 |
NF-B | nuclear factor kappa-light-chain-enhancer of activated B cells |
Bcl-2 | B-cell lymphoma 2 |
TNF | tumor necrosis factor |
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Sweetener Type | Targeted Metabolites/Proteins/Genes/Pathway | Targeted Disease/Tissue | Mechanism of Action | Methods of Testing | Model Used | References | |
---|---|---|---|---|---|---|---|
In Vivo | In Vitro | ||||||
Steviol glycosides | Apoptosis Cellular proliferation | Gastric cancer Colon cancer | - It inhibited mitochondrial apoptotic pathway - Activated p21 and p53 - It increased Bax/Bcl-2 ratio | MTT assay Western blot miRNA analysis Flow cytometry | - HGC-27 cells - Caco-2 cells - HCT-8 cells - HCT 116 cells - MKN-45 cells - MGC-803 cells | [67] | |
Cytotoxic Apoptosis | Stomach cancer | - Induced apoptosis cell death - Increased cytotoxicity | MTT assay Apoptotic assays Flow cytometry | - AZ521 cells | [70] | ||
Apoptosis | Colon cancer | - It decreased cell viability in colorectal cancer cell line | MTT assay Bicinchoninic acid assay | - Wistar rats | - Caco-2 cells | [69] | |
Neohesperidin dihydrochalcone | Apoptosis Angiogenesis | Colon cancer | - It induced apoptosis and blocked angiogenesis - It altered the gut microbiota | PCR Western blot Luciferase assay Cell survival assay TUNEL assay | - C57BL/6 J - APCmin/+ mice | - HCT116 cells - SW480 cells - CT26 cells | [78] |
Glycyrrhizin | Apoptosis | Colon cancer | - Inhibited cellular growth in a dose-dependent manner - It also induced apoptosis through nuclear fragmentation and chromatin condensation | Transmission electron microscopy Apoptotic assay Cell invasion assay Western blot | - SW48 cells | [72] | |
Apoptosis Inflammation | Colon cancer | - Treatment with glycyrrhizic acid suppressed the development of early markers of colon cancer - It also suppressed the development of precancerous lesions - Suppressed the immunostaining of NF-Kb and p65 | Immunohistochemical staining ELISA Aberrant Crypt Foci (ACF) assay | - Albino rats | [75] | ||
Inflammation | Colon cancer | - It reduced the plasma level of IL-6 and TNF-a - It significantly reduced the expression of 8- NitroG, 8-OxodG, COX-2, and HMGB1 | ELISA Immunohistochemical staining | - ICR mice | [95] | ||
Apoptosis Inflammation | Colon cancer | - Treatment with glycyrrhizic acid reduced the expression of NF-kB and COX-2 - It enhanced the expression of cleaved caspase 3 - It also reduced the infiltration of mast cells | ELISA Immunohistochemical staining Mast cell staining | - Albino rats | [76] | ||
Apoptosis Cellular proliferation | Gastric cancer | - Treatment with glycyrrhizic acid downregulated the level of G1 phase-related proteins in a dose- and time-dependent manner - It also upregulated the levels of Bax; cleaved PARP; and pro-caspase-3, -8, -9 | CCK-8 assay Apoptotic assay EdU assay Cell cycle assay Western blot | - MGC-803 cells - BGC-823 cells - SGC-7901 cells | [77] | ||
Saccharin | Apoptosis Cell viability | Intestinal epithelium | - At a lower concentration (up to 100 uM), it induced apoptosis, while at a higher concentration (<=1000 uM), it induced cell death - Decreased cell viability and disrupted the intestinal epithelial barrier through binding to the sweet taste receptors | RT-PCR Annexin V assay siRNA and cDNA Transfections ROS assay ELISA | - C57BL/6 mice | - Caco-2 cells | [93] |
Sucralose | Inflammation | Colitis-associated colorectal cancer | - Significantly increased the number and size of colorectal tumors - Increased expression of TNFa and TLR4 - Increased the abundance of Firmicures, Clostridium symbiosum, and Peptostreptococcus anaerobius while decreasing the abundance of Solobacterium moorei and Bifidobacteria | Spectrophotometry qRT-PCR Western blot ELISA | - C57BL/6 mice | [94] |
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AL-Ishaq, R.K.; Kubatka, P.; Büsselberg, D. Sweeteners and the Gut Microbiome: Effects on Gastrointestinal Cancers. Nutrients 2023, 15, 3675. https://doi.org/10.3390/nu15173675
AL-Ishaq RK, Kubatka P, Büsselberg D. Sweeteners and the Gut Microbiome: Effects on Gastrointestinal Cancers. Nutrients. 2023; 15(17):3675. https://doi.org/10.3390/nu15173675
Chicago/Turabian StyleAL-Ishaq, Raghad Khalid, Peter Kubatka, and Dietrich Büsselberg. 2023. "Sweeteners and the Gut Microbiome: Effects on Gastrointestinal Cancers" Nutrients 15, no. 17: 3675. https://doi.org/10.3390/nu15173675
APA StyleAL-Ishaq, R. K., Kubatka, P., & Büsselberg, D. (2023). Sweeteners and the Gut Microbiome: Effects on Gastrointestinal Cancers. Nutrients, 15(17), 3675. https://doi.org/10.3390/nu15173675