Fucose Ameliorates Tritrichomonas sp.-Associated Illness in Antibiotic-Treated Muc2-/- Mice.

Kseniya M Achasova,Mariya A Borisova,Elena N Kozhevnikova,Ekaterina A Litvinova

doi:10.3390/ijms221910699

Abstract

The mucus layer in the intestine plays a critical role in regulation of host–microbe interactions and maintaining homeostasis. Disruptions of the mucus layer due to genetic, environmental, or immune factors may lead to inflammatory bowel diseases (IBD). IBD frequently are accompanied with infections, and therefore are treated with antibiotics. Hence, it is important to evaluate risks of antibiotic treatment in individuals with vulnerable gut barrier and chronic inflammation. Mice with a knockout of the Muc2 gene, encoding the main glycoprotein component of the mucus, demonstrate a close contact of the microbes with the gut epithelium which leads to chronic inflammation resembling IBD. Here we demonstrate that the Muc2−/− mice harboring a gut protozoan infection Tritrichomonas sp. are susceptible to an antibiotic-induced depletion of the bacterial microbiota. Suppression of the protozoan infection with efficient metronidazole dosage or L-fucose administration resulted in amelioration of an illness observed in antibiotic-treated Muc2−/− mice. Fucose is a monosaccharide presented abundantly in gut glycoproteins, including Mucin2, and is known to be involved in host–microbe interactions, in particular in microbe adhesion. We suppose that further investigation of the role of fucose in protozoan adhesion to host cells may be of great value.

Highlights

The mammalian gut is inhabited by an enormous number of microorganisms referred to as the gut microbiota
The treatment with the antibiotics resulted in death of 35% of Muc2−/− mice harboring Helicobacter spp. (Hspp) (9 of 14 mice survived, group “Muc2−/−inf Abx-W”)
After the two-week antibiotic treatment, survived Muc2−/− mice demonstrated severe weight loss compared to C57BL/6, which recovered by the end of the experiment (Figure 1A)

Summary

Introduction

The mammalian gut is inhabited by an enormous number of microorganisms referred to as the gut microbiota. The barrier prevents close interaction between the gut microbiota and the mucosal immune system, precluding excessive immune activation. A breakdown of this barrier leads to a close interaction between the gut microbes and the immune system resulting in the disturbance of the intestinal homeostasis. This might be followed by different pathological conditions, such as IBD, which comprises Crohn’s disease (CD) and ulcerative colitis (UC) [4]. A disruption of the gut barrier may be caused by miscellaneous factors including genetic predisposition, environmental factors (such as nutrition, drug treatment, stress, etc.), status of the immune system and the microbiota [5]. The precise etiology of such mucus disruptions is currently unknown and considered to be caused either by genetic factors, or inflammatory response and dysbiosis [14]

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Results

Discussion

Conclusion