Although it is known that human gut (HG) microbiome diversity displays differences between healthy and non-healthy individuals, differences between healthy and pathogenic tissues on the same individual are not well studied. Here we tried to examine these changes in correlation with different large intestine (LI) parts and the presence of different types of polypsand lesions. Flexible sigmoidoscopy or Colonoscopy biopsies from macroscopically normal and adnormal tissues (polypoid), along with medical records, were collected from 16individuals (Av. age 67.8 ± 6.02 years, average BMI 24.7 ± 64.00 kg/m²) from Ippokrateio general Hospital of Thessaloniki (Gastrenterology Lab) and “Konstantopouleio – Patission” General Hospital. Tissues DNA extraction and illumina sequencing using Bacteria specific primers was performed, followed by taxonomic and statistical analysis. All samples were characterized by the dominance of Firmicutes, Proteobacteria,Bacteroidetes and Actinobacteria that are the main Phyla observed in HG. However differences were observed between different LI parts as well as between healthy and polyps gut tissues. Cluster analysis based on Horn similarities exhibited low similarities between individuals (<60%) while small polyps (<0.8 cm) samples along with therespective healthy tissues from sigmoid and rectum were grouped with similarities >50 %, similarly to respective samples from the cecum. The rest of the samples including large and low dysplasia polyps along with the respective healthy tissues were grouped in separate pairs or small groups and exhibited much lower similarities. Taxonomic analysis revealed severalgenera that were prevalent and were significantly different between groups. Lachnospiraceae species and Blautia were increased in cecum samples, while in sigmoid and rectum samples Bacteroides was more prevalent. For the large polyps and lesion samples, bacteria such as Streptococcus and Staphylococcus,common in human microbiome, were disproportionally increased in lesion biopsies probably due to their ability to enhance host cell proliferation. In some lesion cases,species such as Methylorubrum, Terrisporobacter or Finegoldia,were found to be significantly enhanced. Most importantly these species were also enhanced in the respective healthy samples implying their importance for potential biomarkers for precancerous stages.