A study published within the journal Cell demonstrates that dietary sugar increases the danger of metabolic syndrome by disrupting gut microbiota and suppressing protective T helper 17 (Th17) cells.

Study: Microbiota imbalance induced by dietary sugar disrupts immune-mediated protection from metabolic syndrome. Image Credit: Alpha Tauri 3D Graphics/Shutterstock

Background

Consumption of a high-fat food regimen increases the danger of diabetes, obesity, heart problems, and metabolic syndrome. Although the causative link between a high-fat food regimen and metabolic risk isn’t completely known, it has been hypothesized that diet-induced intestinal inflammation is usually a potential contributor.

The intestinal immune system is thought to be an important regulator of metabolic homeostasis. CD4 T cells are major regulators of intestinal immune responses to dietary antigens. Studies have identified certain cell types that exhibit each promoting and protective effects in metabolic syndrome. These cell types are Th17 cells and kind 3 innate lymphoid cells (ILC3).

The gut microbiota plays an important role in regulating intestinal immune responses, including Th17 cell and ILC3 responses. High-fat diet-induced changes in gut microbiota composition is thought to advertise metabolic syndrome by altering energy metabolism and immune responses.

In the present study, scientists have determined the connection between microbiota-controlled intestinal immune responses and diet-induced obesity and metabolic syndrome.

Impact of a high-fat food regimen in metabolic syndrome

The comparison of immune responses induced by standard food regimen and high-fat food regimen in mice revealed that high-fat food regimen induces the symptoms of metabolic syndrome, including body weight gain, insulin resistance, and glucose intolerance.

Regarding intestinal immunity, high-fat food regimen was found to significantly reduce the expression and functionality of Th17 cells. The food regimen also reduced the secretion of interleukin 17 (IL-17), a cytokine produced by Th17 cells.

Mechanistically, high-fat food regimen caused a rapid lack of commensal microbiota answerable for inducing Th17 cells. This subsequently led to significant depletion of Th17 cells before the event of metabolic syndrome.

Further experiments revealed that commensal microbiota-induced Th17 cells play a vital role in ensuring microbiota-mediated protection against high-fat diet-related obesity and metabolic syndrome.

Impact of dietary sugar in metabolic syndrome

Three major harmful components of high-fat food regimen include excess fat, low dietary fiber, and high sugar content. Of those components, high level of sugar was identified because the fundamental causal factor of diet-induced obesity and metabolic syndrome.

Mechanistically, dietary sugar promoted the expansion of Faecalibaculum rodentium in an ILC3-dependent manner. The overgrowth of this Gram-positive bacterium displaced the commensal gut microbiota, resulting in a depletion of intestinal commensal Th17 cells and subsequent diet-mediated induction of obesity and metabolic syndrome in mice.

Nevertheless, the findings revealed that the elimination of dietary sugar isn’t sufficient to make sure protection. Restoration of Th17 expression and functionality by immune therapies can be required to guard the mice against diet-induced metabolic complications.

Th17 cell-mediated protection against metabolic syndrome

Absorption of dietary lipid by intestinal epithelial cells is a known regulator of metabolic syndrome. Th17 cell-secreting cytokine IL-17 is thought to keep up intestinal barrier integrity by regulating epithelial cells.

The lipid content measurement in various tissues of mice fed with a high-fat food regimen revealed that within the presence of Th17 cells, intestinal epithelial cells absorb a lesser amount of dietary lipid. Mechanistically, Th-17 cell-secreted IL-17 suppressed the epithelial expression of fatty acid transporter CD36, resulting in reduced lipid uptake and absorption across the intestinal epithelium.  

Study significance

The study provides an interactome of dietary components, gut microbiota, and intestinal immune cells that regulate the pathophysiology of high-fat diet-induced metabolic complications, corresponding to obesity, type 2 diabetes, and metabolic syndrome.

The study identifies dietary sugar as the key deleterious component of a high-fat food regimen to extend the danger of metabolic disorders. Based on the findings, dietary modifications, along with immune interventions, are required to make sure full protection against diet-induced metabolic disorders.

As mentioned by the scientists, the study only focuses on the early stages of metabolic changes induced by a high-fat food regimen. Since diet-induced intestinal inflammation doesn’t occur at early time points, future studies are required to decipher the long-term effects and protective mechanisms of Th17 cells in systemic disease.