Excessive intake of sugar: An accomplice of inflammation

Abstract

High sugar intake has long been recognized as a potential environmental risk factor for increased incidence of many non-communicable diseases, including obesity, cardiovascular disease, metabolic syndrome, and type 2 diabetes (T2D). Dietary sugars are mainly hexoses, including glucose, fructose, sucrose and High Fructose Corn Syrup (HFCS). These sugars are primarily absorbed in the gut as fructose and glucose. The consumption of high sugar beverages and processed foods has increased significantly over the past 30 years. Here, we summarize the effects of consuming high levels of dietary hexose on rheumatoid arthritis (RA), multiple sclerosis (MS), psoriasis, inflammatory bowel disease (IBD) and low-grade chronic inflammation. Based on these reported findings, we emphasize that dietary sugars and mixed processed foods may be a key factor leading to the occurrence and aggravation of inflammation. We concluded that by revealing the roles that excessive intake of hexose has on the regulation of human inflammatory diseases are fundamental questions that need to be solved urgently. Moreover, close attention should also be paid to the combination of high glucose-mediated immune imbalance and tumor development, and strive to make substantial contributions to reverse tumor immune escape.

Keywords: IL-1beta; TGF-beta; Th17 cells (Th17); autoimmune disorders; low-grade chronic inflammation; macrophages.

Figure 1

Excessive consumption of dietary sugars is closely related to the occurrence and development of inflammation.

Figure 2

Dietary sugars-mediated T cell inflammation. Excess dietary sugars may activate TGFβ through mtROS post entering T cells, and together with IL-6 in the immune microenvironment, the expression of transcription factor RORγt is induced to promote Th17 cell differentiation.

Figure 3

Regulation of the gut microbiome by dietary sugars. Excessive consumption of dietary sugars reduces the production of short-chain fatty acids in the gut, which can lead to impaired gut barriers. This results in a rapid increase in infiltration of neutrophils while accelerating the transfer of Parabacteroides, ie, lipopolysaccharide (LPS). The binding of LPS to TOLL-like receptor 4 (TLR4) activates the nuclear factor-κB (NF-κB) signaling pathway, and finally induces the production of inflammatory factors IL-6, IL-1β and TNF-α. On the other hand, the excessive dietary sugar content makes Bacillus fragilis and Prevotella abundant, thereby destroying the intestinal mucosa. In the meanwhile, the relative abundance of sugar-soluble bacteria Sutterellaceae increased while the abundance of Lachnospiraceae and Lactobacillaceae, which belonged to Firmicutes, decreased, eventually increasing the levels of inflammatory cytokines IL-6, TNF-a, Lcn2 and Cox2. Increased neutrophil infiltration and inflammatory factor production aggravate the occurrence and development of IBD.

Figure 4

Dietary sugars-mediated inflammation in macrophages. High levels of dietary sugars lead to increased TOLL-like receptor 4 (TLR4) activity, which subsequently activates downstream the nuclear factor-κB (NF-κB) and MAPK signaling pathways, thereby promoting the upregulation of inflammatory factors IL-6, IL-1β and TNF-α. In addition, dietary sugars-mediated inflammation in dendritic cells and neutrophils is also accomplished by activating TLR4.