A study published in the journal Cell shows that dietary sugar increases the risk of metabolic syndrome by altering gut microbiota and suppressing protective T helper 17 (Th17) cells.
Study: Microbiota Imbalance Induced by Dietary Sugar Alters Immune Protection in Metabolic Syndrome. Image credit: Alpha Tauri 3D Graphics/Shutterstock
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Eating a high-fat diet increases the risk of diabetes, obesity, cardiovascular disease and metabolic syndrome. Although the causal link between a high-fat diet and metabolic risk is not fully known, it has been hypothesized that diet-induced intestinal inflammation may be a potential contributor.
The intestinal immune system is considered a vital regulator of metabolic homeostasis. CD4 T cells are major regulators of intestinal immune responses to dietary antigens. Studies have identified certain types of cells that have both promoting and protective effects in metabolic syndrome. These cell types are Th17 cells and innate lymphoid type 3 cells (ILC3).
The gut microbiota plays a crucial role in regulating gut immune responses, including Th17 and ILC3 cell responses. High-fat diet-induced changes in gut microbiota composition are known to promote metabolic syndrome by altering energy metabolism and immune responses.
In the current study, the scientists determined the relationship between gut immune responses controlled by the microbiota and diet-induced obesity and metabolic syndrome.
Impact of a high-fat diet on the metabolic syndrome
Comparison of immune responses induced by standard diet and high-fat diet in mice revealed that high-fat diet induces symptoms of metabolic syndrome, including body weight gain, insulin resistance, and glucose intolerance.
Regarding gut immunity, high-fat diet was found to significantly reduce the expression and functionality of Th17 cells. The diet also reduced the secretion of interleukin 17 (IL-17), a cytokine produced by Th17 cells.
Mechanistically, the high-fat diet caused a rapid loss of commensal microbiota responsible for inducing Th17 cells. Subsequently, this led to a significant depletion of Th17 cells before the development of metabolic syndrome.
Further experiments revealed that Th17 cells induced by commensal microbiota play an essential role in ensuring microbiota-mediated protection against high-fat diet-related obesity and metabolic syndrome.
Impact of dietary sugar on the metabolic syndrome
The three main harmful components of the high-fat diet include excess fat, low dietary fiber, and high sugar content. Of these components, high sugar was identified as the main causal factor in diet-induced obesity and metabolic syndrome.
Mechanistically, dietary sugar promoted the growth of Faecalibaculum rodentium in an ILC3-dependent manner. Overgrowth of this Gram-positive bacterium displaced the commensal gut microbiota, leading to depletion of gut commensal Th17 cells and subsequent induction of diet-mediated obesity and metabolic syndrome in mice.
However, the findings revealed that eliminating dietary sugar is not enough to ensure protection. Restoration of Th17 expression and functionality by immune therapies is also required to protect mice against diet-induced metabolic complications.
Th17 cell-mediated protection against metabolic syndrome
Uptake of dietary lipids by intestinal epithelial cells is a known regulator of the metabolic syndrome. The Th17 cell secretory cytokine IL-17 is known to maintain the integrity of the intestinal barrier by regulating epithelial cells.
Measurement of lipid content in various tissues of mice fed a high-fat diet revealed that, in the presence of Th17 cells, intestinal epithelial cells take up less dietary lipid. Mechanistically, IL-17 secreted by Th-17 cells suppressed epithelial expression of the fatty acid transporter CD36, resulting in reduced lipid uptake and absorption across the intestinal epithelium.
Study the importance
The study provides an interactome of dietary components, gut microbiota, and gut immune cells that regulate the pathophysiology of high-fat diet-induced metabolic complications such as obesity, type 2 diabetes, and metabolic syndrome.
The study identifies dietary sugar as the main harmful component of a high-fat diet in increasing the risk of metabolic disorders. Based on the findings, dietary modifications, along with immune interventions, are required to ensure full protection against diet-induced metabolic disorders.
As the scientists mentioned, the study only focuses on the early stages of the metabolic changes induced by a high-fat diet. Because diet-induced intestinal inflammation does not occur early, future studies are required to decipher the long-term effects and protective mechanisms of Th17 cells in systemic disease.