Digestive Diseases and Sciences

, Volume 61, Issue 10, pp 2908–2920 | Cite as

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

  • Eugene Dogkotenge Kuugbee
  • Xueqi Shang
  • Yaser Gamallat
  • Djibril Bamba
  • Annoor Awadasseid
  • Mohammed Ahmed Suliman
  • Shizhu Zang
  • Yufang Ma
  • Gift Chiwala
  • Yi Xin
  • Dong Shang
Original Article

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.

Keywords

Colorectal cancer Lactobacillus Bifidobacteria Probiotics Microbiota Toll-like receptors (TLRs) 

Notes

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.

Compliance with ethical standards

Conflict of interest

Authors confirm that there is no conflict of interest.

Supplementary material

10620_2016_4238_MOESM1_ESM.tif (2 mb)
Supplementary Figure 1Haematoxylin and Eosin staining; (A) representative normal colon mucosa and (B) Representative cancer of the colon show high grade adenocarcinoma (TIFF 2043 kb)
10620_2016_4238_MOESM2_ESM.tif (3.5 mb)
Supplementary Figure 2Immunohistochemistry 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)
10620_2016_4238_MOESM3_ESM.docx (16 kb)
Supplementary material 3 (DOCX 15 kb)
10620_2016_4238_MOESM4_ESM.docx (21 kb)
Supplementary material 4 (DOCX 20 kb)

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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Eugene Dogkotenge Kuugbee
    • 1
    • 6
  • Xueqi Shang
    • 1
  • Yaser Gamallat
    • 1
  • Djibril Bamba
    • 1
  • Annoor Awadasseid
    • 1
  • Mohammed Ahmed Suliman
    • 2
  • Shizhu Zang
    • 3
  • Yufang Ma
    • 4
  • Gift Chiwala
    • 1
  • Yi Xin
    • 1
  • Dong Shang
    • 5
  1. 1.Department of Biochemistry and Molecular BiologyDalian Medical UniversityDalianChina
  2. 2.Department of Clinical BiochemistryDalian Medical UniversityDalianChina
  3. 3.Department of BiotechnologyDalian Medical UniversityDalianChina
  4. 4.Department of Acute Abdominal SurgeryFirst Affiliated Hospital of Dalian Medical UniversityDalianChina
  5. 5.Department of MicrobiologyDalian Medical UniversityDalianChina
  6. 6.Laboratory DepartmentTamale Teaching HospitalTamaleGhana

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