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The power of your gut

Fat, sugar, and metabolic disease: links between the gut microbiota and immunity

Metabolic disorder
The gut microbiota

We already knew that too much fat and sugar promotes obesity and type 2 diabetes. Now we also know that the gut microbiota and its immune system play a role in regulating the metabolism. Deciphering the mechanisms involved has been no small task, but researchers have recently succeeded in doing so1, revealing the major role played by excessive sugar.

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Sources

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About this article

Created 20 December 2022
Updated 02 January 2023

It’s all common sense. Often too rich in fat and sugar, the “ (sidenote: Western diet Diet rich in processed foods, refined sugar, salt, saturated fats (red meats) and trans fats (pastries) Zinöcker MK, Lindseth IA. The Western Diet-Microbiome-Host Interaction and Its Role in Metabolic Disease. Nutrients. 2018 Mar 17;10(3):365.  ) ” diet has an impact on our health. It tends to increase inflammation in the body and to disrupt the metabolism. It can thus lead to obesity, type 2 diabetes, and metabolic syndrome. Numerous studies have shown that the gut microbiota and its immune system play a major role in metabolic balance, with disturbances in the gut converting excess food into extra pounds and serious illnesses.

More fat and sugar means less gut immune cells to balance the metabolism 

To better understand these disturbances, researchers fed mice a diet rich in fat and sugar for four weeks. As expected, in addition to gaining more weight than mice fed normally, these overfed mice also developed a (sidenote: Metabolic syndrome Combination of several metabolic anomalies: high blood pressure, large waist circumference, increased blood triglyceride and glucose levels associated to a low blood level of “good” cholesterol. Alberti KG, Zimmet P, Shaw J. The metabolic syndrome--a new worldwide definition. Lancet. 2005 ; 366 (9491) : 1059-62. ) . An analysis of the mice’s gut flora via their droppings showed that this diet caused a rapid loss of (sidenote: Segmented filamentous bacteria Segmented filamentous bacteria (SFB) are bacteria of the Clostridiaceae family that colonize the gut of many vertebrate and invertebrate animals without causing an inflammatory response. On the contrary, their presence is thought to stimulate the immune response. They help in the differentiation and maturation of certain defense cells and promote the elimination of pathogenic microbes.  Hedblom GA, Reiland HA, Sylte MJ, et al. Segmented filamentous bacteria–metabolism meets immunity. Frontiers in microbiology. 2018 Aug 24;9:1991.  https://www.frontiersin.org/articles/10.3389/fmicb.2018.01991/full   ) . This in turn reduced the production of (sidenote: T helper 17 (Th17) cells Th17 cells are immune system cells that play a role in host defense against pathogens, particularly at epithelial barriers, such as the gut barrier. Awasthi A, Kuchroo VK (2009) Th17 cells: From precursors to players in inflammation and infection. Int Immunol 21:489–498. ) , subsequent to which the metabolic syndrome appeared. 

The researchers found that Th17 cells regulate the absorption of lipids in the gut and are necessary for protection against metabolic syndrome. The loss of Th17 cells is thus to blame for the adverse health effects of a diet high in fat and sugar. By administering segmented filamentous bacteria to the overfed mice, Th17 production was restored. As a result, the mice lost weight and their metabolism improved.

Sugar, the metabolism’s worst enemy 

But which is most to blame, too much fat or too much sugar? The effects of a diet rich in fat and sugar (including sucrose and maltodextrin, common in candy and soda) were compared with those of a diet rich in fat but low in sugar. The researchers found that sugar on its own modifies the composition of the gut microbiota to the detriment of the segmented filamentous bacteria that stimulate Th17 cells. So would it be enough to eliminate sugar from the diet to ensure protection against metabolic disease? Not entirely, according to the researchers, since protection also requires the presence of the Th17 cells produced by the gut microbiota.

In short, metabolic syndrome, obesity, and type 2 diabetes are the result of complex interactions between diet, the gut microbiota, and immunity. According to the researchers, there is no “universal” diet that would produce the desired effect in everyone. Instead, a personalized approach to metabolic disorders is required. In the future, such approaches could take into account inter-individual differences in the gut microbiota’s immune system.

Sources

1. Kawano Y, Edwards M, Huang Y, et al. Microbiota imbalance induced by dietary sugar disrupts immune-mediated protection from metabolic syndrome. Cell. 2022;185(19):3501-3519.e20

Tags
Food Obesity Sugar Diet Diabetes Immunity Metabolic syndrome

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    See also

    When sweeteners undermine blood sugar control and disrupt the microbiota
    The gut microbiota: a new direction for treating type 2 diabetes?
    Created 20 December 2022
    Updated 02 January 2023

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