Dietary sugar can disrupt the gut microbiota and cause metabolic complications

Dietary sugar can disrupt the gut microbiota and cause metabolic complications

A study published in the journal cell shows that dietary sugar increases the risk of metabolic syndrome by disrupting the gut microbiota and suppressing protective T helper 17 (Th17) cells.

Lernen: Ein durch Nahrungszucker verursachtes Ungleichgewicht der Mikrobiota stört den immunvermittelten Schutz vor dem metabolischen Syndrom. Bildnachweis: Alpha Tauri 3D Graphics/Shutterstock

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Consuming a high-fat diet increases the risk of diabetes, obesity, cardiovascular disease and metabolic syndrome. Although the causal relationship 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 factor.

The intestinal immune system is considered a vital regulator of metabolic homeostasis. CD4 T cells are important regulators of the intestinal immune response to dietary antigens. Studies have identified specific cell types that have both promotive and protective effects in metabolic syndrome. These cell types are Th17 cells and innate lymphoid cells type 3 (ILC3).

The gut microbiota plays a critical role in regulating intestinal immune responses, including Th17 cell and ILC3 responses. Changes in gut microbiota composition caused by a high-fat diet are known to promote metabolic syndrome by altering energy metabolism and immune responses.

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

Effects of a high-fat diet in metabolic syndrome

Comparison of immune responses induced by standard diet and high-fat diet in mice showed that high-fat diet induces the symptoms of metabolic syndrome, including body weight gain, insulin resistance and glucose intolerance.

Regarding intestinal immunity, a high-fat diet has been 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, a high-fat diet caused a rapid loss of the commensal microbiota responsible for the induction of Th17 cells. This subsequently led to a significant depletion of Th17 cells prior to the development of metabolic syndrome.

Further experiments showed that Th17 cells induced by commensal microbiota play an essential role in ensuring microbiota-mediated protection against high-fat diet and metabolic syndrome.

Influence of dietary sugar in metabolic syndrome

The three main harmful components of a high-fat diet are excess fat, low fiber and high sugar. Of these components, high sugar levels have been identified as a major cause of diet-induced obesity and metabolic syndrome.

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

However, the results showed that eliminating sugar from the diet is not enough to ensure protection. Restoring Th17 expression and functionality through immunotherapies is also required to protect mice from 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. The cytokine IL-17, secreted by Th17 cells, is known to maintain the integrity of the intestinal barrier by regulating epithelial cells.

Measuring lipid content in various tissues of mice fed a high-fat diet revealed that intestinal epithelial cells absorb a lower amount of dietary lipid in the presence of Th17 cells. Mechanistically, IL-17 secreted by Th-17 cells suppressed the epithelial expression of the fatty acid transporter CD36, resulting in reduced lipid uptake and absorption by the intestinal epithelium.

Study meaning

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 such as obesity, type 2 diabetes and metabolic syndrome.

The study identifies dietary sugar as the main harmful component of a high-fat diet for increasing the risk of metabolic disorders. Based on the evidence, dietary modifications along with immune interventions are required to ensure complete 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 diet. Because diet-induced intestinal inflammation does not occur at early time points, future studies are needed to decipher the long-term effects and protective mechanisms of Th17 cells in systemic diseases.

Reference:

• Kawano Y. (2022). Ein durch Nahrungszucker verursachtes Ungleichgewicht der Mikrobiota stört den immunvermittelten Schutz vor dem metabolischen Syndrom. Zelle. doi: https://doi.org/10.1016/j.cell.2022.08.005 https://www.sciencedirect.com/science/article/abs/pii/S0092867422009928?dgcid=author