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Structural Change in Microbiota by a Probiotic Cocktail Enhances the Gut Barrier and Reduces Cancer via TLR2 Signaling in a Rat Model of Colon Cancer

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Abstract

Background

Structural change in the gut microbiota is implicated in cancer. The beneficial modulation of the microbiota composition with probiotics and prebiotics prevents diseases.

Aim

We investigated the effect of oligofructose–maltodextrin-enriched Lactobacillus acidophilus, Bifidobacteria bifidum, and Bifidobacteria infantum (LBB), on the gut microbiota composition and progression of colorectal cancer.

Methods

Sprague Dawley rats were acclimatized, given ampicillin (75 mg/kg), and treated as follows; GCO: normal control; GPR: LBB only; GPC: LBB+ 1,2-dimethylhydrazine dihydrochloride (DMH); and GCA: DMH only (cancer control). 16S V4 Pyrosequencing for gut microbiota analysis, tumor studies, and the expression of MUC2, ZO-1, occludin, TLR2, TLR4, caspase 3, COX-2, and β-catenin were conducted at the end of experiment.

Results

Probiotic LBB treatment altered the gut microbiota. The relative abundance of genera Pseudomonas, Congregibacter, Clostridium, Candidactus spp., Phaeobacter, Escherichia, Helicobacter, and HTCC was decreased (P < 0.05), but the genus Lactobacillus increased (P < 0.05), in LBB treatment than in cancer control. The altered gut microbiota was associated with decreased tumor incidence (80 % in GPC vs. 100 % in GCA, P = 0.0001), tumor volume (GPC 84.23 (42.75–188.4) mm3 vs. GCA 243 (175.5–344.5) mm3, P < 0.0001) and tumor multiplicity/count (GPC 2.92 ± 0.26 vs. GCA 6.27 ± 0.41; P < 0.0001). The expression of MUC2, ZO-1, occludin, and TLR2 was increased, but expression of TLR4, caspase 3, Cox-2, and β-catenin was decreased by LBB treatment than in cancer control GCA (P < 0.05).

Conclusion

Administration of LBB modulates the gut microbiota and reduces colon cancer development by decreasing tumor incidence, multiplicity/count, and volume via enhanced TLR2-improved gut mucosa epithelial barrier integrity and suppression of apoptosis and inflammation.

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Acknowledgments

We thank the anonymous reviewers for their valuable comments that were helpful in our work. The study was supported by National Natural Science Foundation of China (81373875).

Author contributions

EK and XY designed and conceived the study. EK, SX, AA, YG, BD, CG, and SM performed the experiment. EK, SZ, and MY analyzed the results. EK, XY, and SD wrote the manuscript. All authors read and approved the final manuscript.

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, Dalian Medical University, Dalian, 116044, China

    Eugene Dogkotenge Kuugbee, Xueqi Shang, Yaser Gamallat, Djibril Bamba, Annoor Awadasseid, Gift Chiwala & Yi Xin

  2. Department of Clinical Biochemistry, Dalian Medical University, Dalian, 116044, China

    Mohammed Ahmed Suliman

  3. Department of Biotechnology, Dalian Medical University, Dalian, 116044, China

    Shizhu Zang

  4. Department of Acute Abdominal Surgery, First Affiliated Hospital of Dalian Medical University, Dalian, 116011, China

    Yufang Ma

  5. Department of Microbiology, Dalian Medical University, Dalian, 116044, China

    Dong Shang

  6. Laboratory Department, Tamale Teaching Hospital, Post Office Box 16, Tamale, Ghana

    Eugene Dogkotenge Kuugbee

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  1. Eugene Dogkotenge Kuugbee
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Supplementary Figure 1

Haematoxylin and Eosin staining; (A) representative normal colon mucosa and (B) Representative cancer of the colon show high grade adenocarcinoma (TIFF 2043 kb)

Supplementary Figure 2

Immunohistochemistry of COX-2 of colon from GPR, GPC, GCA and GCA. Probiotic LBB deceased COX-2 expression compared with GCA. #GCO: Normal control; GPR: Probiotic LBB only; GPC: Probiotic LBB and Cancer; GCA: Cancer Control (TIFF 3597 kb)

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Kuugbee, E.D., Shang, X., Gamallat, Y. et al. Structural Change in Microbiota by a Probiotic Cocktail Enhances the Gut Barrier and Reduces Cancer via TLR2 Signaling in a Rat Model of Colon Cancer. Dig Dis Sci 61, 2908–2920 (2016). https://doi.org/10.1007/s10620-016-4238-7

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