Diet Rich in Simple Sugars Promotes Pro-Inflammatory Response via Gut Microbiota Alteration and TLR4 Signaling.

Alena Fajstova,Helena Tlaskalova-Hogenova,Tomas Hrncir,Jana Malkova,Martin Kostovcik,Stepan Coufal,Martina Cermakova,Miloslav Kverka,Klara Kostovcikova,Helena Pelantova,Blanka Sediva,Natalie Galanova,Marek Kuzma,Tomas Hudcovic

doi:10.3390/cells9122701

Abstract

Diet is a strong modifier of microbiome and mucosal microenvironment in the gut. Recently, components of western-type diets have been associated with metabolic and immune diseases. Here, we studied how high-sugar diet (HSD) consumption influences gut mucosal barrier and immune response under steady state conditions and in a mouse model of acute colitis. We found that HSD significantly increased gut permeability, spleen weight, and neutrophil levels in spleens of healthy mice. Subsequent dextran sodium sulfate administration led to severe colitis. In colon, HSD significantly promoted neutrophil infiltration and increased the levels of IL-6, IL-1β, and TNF-α. Moreover, HSD-fed mice had significantly higher abundance of pathobionts, such as Escherichia coli and Candida, in fecal samples. Although germ-free mice colonized with microbiota of conventionally reared mice that consumed different diets had equally severe colitis, mice colonized with HSD microbiota showed markedly increased infiltration of neutrophils to the gut. The induction of colitis in Toll-like receptor 4 (TLR4)-deficient HSD-fed mice led to significantly milder colitis than in wild-type mice. In conclusion, our results suggested a significant role of HSD in disruption of barrier integrity and balanced mucosal and systemic immune response. In addition, these processes seemed to be highly influenced by resident potentially pathogenic microbiota or metabolites via the TLR4 signaling pathway.

Highlights

Saccharides constitute the greatest proportion of our daily food intake
We focused on the influence of a high-sucrose diet (HSD) and a high-fiber diet (HFiD) on intestinal barrier function, interaction with gut microbiota, and mucosal and systemic immune response in healthy mice and in mouse models of acute and chronic colitis
Compared with control diet (CD)-fed mice, mice fed with high-sugar diet (HSD) had generally higher state of immune system activation, as demonstrated by increased proportion of both neutrophils and Th17 cells in the spleen or increased proportions of both resident (Ly6Clow ) and pro-inflammatory (Ly6Chigh )

Summary

Introduction

Today’s high consumption of simple refined sugars and lack of complex polysaccharides, such as fiber, are typical features of westernized diets [1]. The consumption of foods rich in simple or added sugars grew in high-income countries, and in middle- and low-income countries [2]. Studies in various animal models have revealed that high sugar intake influences the development of allergy [6], hypertension, and insulin resistance [7] and causes cognitive decline [8,9,10,11] and can affect the whole organism, for instance, by increasing oxidative stress [12,13,14].

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Conclusion