**5. Conclusions**

In summary, our findings provide the following new insights. RSCC and LSCC harbor distinct niches and have different microbiome compositions. The presence of a colonic tumor leads to a more consistent cancer-defined microbiome and shapes the normal spatial heterogeneity existing along the intestinal tract. The tumor microbiome may contribute towards shaping a favorable microbiome across the large intestine border into the ileum and also in LSCC. The stool microbiome only partly reflects the microbiome landscape of patients with CC. Mechanical bowel preparation and perioperative antibiotics together with surgery resulted in major changes in the stool microbiome, characterized by a significant increase in the abundance of potentially pathogenic bacteria, such as *Enterococcus*.

We believe that regarding CC and RC as two different tumor entities is fundamental to overcoming the inconsistent study results and the heterogeneous nature of microbiomes. Overall, our results have implications for understanding the role and impact of the microbiome in right- and left-sided CC.

**Supplementary Materials:** The following supporting information can be downloaded at: https: //www.mdpi.com/article/10.3390/ijms24043265/s1.

**Author Contributions:** M.L. and S.K. initiated the study and were responsible for the study design. The authors responsible for data collection were B.K., M.G. and M.L. B.K. performed the experiments as part of her doctoral thesis and was assisted by S.W. The original draft was written by B.K., S.K. and M.L. S.W., K.W., A.D., M.B., C.K., C.G., A.A., O.T., R.S., R.G., A.R.S. and J.T. critically revised the manuscript. S.K. and M.L. are primarily responsible for the final manuscript. All authors have read and agreed to the published version of the manuscript.

**Funding:** This work was financially supported by the Tumorzentrum Erlangen (ID 3007971).

**Institutional Review Board Statement:** The study was conducted in accordance with the Declaration of Helsinki and approved by the Ethics Committee of the University of Erlangen (Protocol Number: 420\_18 B).

**Informed Consent Statement:** Informed consent was obtained from all subjects involved in the study.

**Data Availability Statement:** The data are available on reasonable request from the corresponding author.

**Conflicts of Interest:** The authors declare no conflict of interest.

## **References**


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