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. 2021 Oct 2;22(19):10699.
doi: 10.3390/ijms221910699.

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

Kseniya M Achasova  1   2   3 , Elena N Kozhevnikova  1   2   3   4 , Mariya A Borisova  5 , Ekaterina A Litvinova  1   2
Affiliations

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

Kseniya M Achasova et al. Int J Mol Sci. .

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.

Keywords: Mucin2; antibiotic; fucose; inflammation; microbiome; protozoa.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
The antibiotic treatment induced mortality of Muc2−/− mice. (A) Body weight dynamics during the antibiotic treatment. *, **—“C57BL/6 Abx-W” vs. “Muc2−/−inf Abx-W”, p < 0.05, p < 0.01, Mann–Whitney u-test. (B) Survival rate. #—“C57BL/6 Abx-W” vs. “Muc2−/−inf Abx-W”, p < 0.05, Fisher Exact test. (C) Azur-II-eosin-stained colonic sections of Muc2−/− mice (treated with the antibiotics and control group). Scale bar = 50µm. (D) Histological score of inflammation in colon of Muc2−/− mice. (E) Gene expression in colon tissue normalized on beta Tubulin (Tubb5) gene. **—differences between groups p < 0.01, Mann–Whitney u-test. (F) Relative abundance of the gut bacteria in feces on the day 15, normalized on Mus musculus 28S rRNA DNA. *, **—differences between groups p < 0.05, p < 0.01, Mann–Whitney u-test. #, ##, ###—differences between groups p < 0.05, p < 0.01, p < 0.001, Fisher Exact test. ND—not detected. Experimental groups: “Abx-W”—treatment with the antibiotics by adding in drinking water.
Figure 2
Figure 2
Protozoan microorganism Tritrichomonas sp. clone Tsp1019 was detected in the intestine of Muc2−/− mice. (A) Micrograph demonstrates microorganism purified from cecal content stained with Hoechst 33258 (magnification ×400), the bright field and Hoechst 33258 are merged. Scale bar = 10 µm. (B) Phylogenetic analysis of 18S rRNA DNA sequence obtained from gut content of Muc2−/− mice. (C) Relative abundance of Tritrichomonas sp. Tsp1019 DNA in feces of Muc2−/− mice on the day 15, normalized on Mus musculus 28S rRNA DNA.
Figure 3
Figure 3
Muc2−/− mice free of the infections survive after the antibiotic treatment. (A) Body weight dynamics upon antibiotic treatment. (B) Survival rate. (C) Gene expression in colon tissue normalized on beta Tubulin (Tubb5) gene. (D) Relative abundance of the gut bacteria in feces on the day 15, normalized on Mus musculus 28S rRNA gene. *, **—differences between groups p < 0.05, p < 0.01, Mann–Whitney u-test. Experimental groups: “Abx-W”—treatment with the antibiotics by adding in drinking water.
Figure 4
Figure 4
Suppression of Tritrichomonas sp. by antibiotic treatment by gavage results in the recovery of the infected Muc2−/− mice. (A) Body weight dynamics upon antibiotic treatment. *, **—“Muc2−/−inf control” vs. “Muc2−/−inf Abx-G”, p < 0.05, p < 0.01, Mann–Whitney u-test. (B) Relative abundance of Tritrichomonas sp. T.sp1019 in feces on the day 15, normalized on Mus musculus 28S rRNA gene. #—differences between groups p < 0.05, Fisher Exact test. ND—not detected. (C) Gene expression in colon tissue normalized on beta Tubulin (Tubb5) gene. **—differences between groups p < 0.01, Mann–Whitney u-test. (D) Relative abundance of the gut bacteria in feces on the day 15, normalized on Mus musculus 28S rRNA gene. **—differences between groups p < 0.01, Mann–Whitney u-test. ND—not detected. Experimental groups: “control”—gavage with drinking water; “Abx-G”—gavage with the antibiotics.
Figure 5
Figure 5
L-fucose suppresses Tritrichomonas sp. and ameliorates antibiotic-induced emaciation in infected Muc2−/− mice. (A) Body weight dynamics upon treatment with antibiotics and L-fucose. *, **—p < 0.05 and p < 0.01, Mann–Whitney u-test. Arrows indicate the days when death was observed. (B) Survival rate. #—p < 0.05, Fisher Exact test. (C) Relative abundance of Tritrichomonas sp. in feces normalized on Mus musculus 28S rRNA DNA. *—differences between groups p < 0.05, Mann–Whitney u-test. (D) Azur-II-eosin-stained colonic sections of Muc2−/− mice (treated with the antibiotics and control group). Scale bar = 50µm. (E) Histological score of inflammation in colon of Muc2−/− mice. (F) Gene expression in colon tissue normalized on beta Tubulin (Tubb5) gene. **—differences compared to mRNA level in control group indicated by dotted line, p < 0.01, Mann–Whitney u-test. Experimental groups: “Abx-W”—treatment with the antibiotics via drinking water for 7 days; “Abx-W/Fuc”—treatment with antibiotics with L-fucose via drinking water for 7 days.
Figure 6
Figure 6
L-fucose prevents an expansion of Tritrichomonas sp. in colon of Muc2−/− mice upon antibiotic-induced microbiota depletion. (A) Relative abundance of Tritrichomonas sp. in colon tissue of Muc2−/− mice after treatment with antibiotics and antibiotics supplemented with L-fucose, normalized on Mus musculus 28S rRNA DNA. *—differences between groups p < 0.05, Mann–Whitney u-test. #—p < 0.05, Fisher Exact test. ND—not detected. (B) Relative abundance of the gut bacteria in feces of Muc2−/− mice after treatment with antibiotics and antibiotics supplemented with L-fucose normalized on Mus musculus 28S rRNA gene. **—differences between groups p < 0.01, Mann–Whitney u-test. (C) Relative abundance of Tritrichomonas sp. in colon tissue of Muc2−/− mice after infection via gavage. (D) Spearman correlation between relative abundance of Tsp1019 in colon tissue and bacteria in feces.
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References

    1. Grigg J.B., Sonnenberg G.F. Host-Microbiota Interactions Shape Local and Systemic Inflammatory Diseases. J. Immunol. 2017;198:564–571. doi: 10.4049/jimmunol.1601621. - DOI - PMC - PubMed
    1. McGuckin M.A., Linden S.K., Sutton P., Florin T.H. Mucin dynamics and enteric pathogens. Nat. Rev. Microbiol. 2011;9:265–278. doi: 10.1038/nrmicro2538. - DOI - PubMed
    1. Okumura R., Takeda K. Maintenance of intestinal homeostasis by mucosal barriers. Inflamm. Regen. 2018;38:5. doi: 10.1186/s41232-018-0063-z. - DOI - PMC - PubMed
    1. Martini E., Krug S.M., Siegmund B., Neurath M.F., Becker C. Mend Your Fences: The Epithelial Barrier and Its Relationship with Mucosal Immunity in Inflammatory Bowel Disease. Cell. Mol. Gastroenterol. Hepatol. 2017;4:33–46. doi: 10.1016/j.jcmgh.2017.03.007. - DOI - PMC - PubMed
    1. Ananthakrishnan A.N. Epidemiology and risk factors for IBD. Nat. Rev. Gastroenterol. Hepatol. 2015;12:205–217. doi: 10.1038/nrgastro.2015.34. - DOI - PubMed

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