Evaluation of multidrug resistance in the Gram-negative microbiome of cancer patients and the adverse effects of their metabolites on albino rats and epithelial or fibroblasts cell lines
Abstract Background Cancer is a significant global health issue due to its high incidence and mortality rates. In recent years, the relationship between the human microbiota and cancer has garnered attention across various medical fields. This includes research into the microbial communities that in...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-01-01
|
| Series: | Infectious Agents and Cancer |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13027-024-00634-y |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832594976693813248 |
|---|---|
| author | Mervat Morsy Abbas Ahmed El-Gendy Huda Ahmed Alghamdi Khaled G. Abdel-Wahhab Nabila S. Hassan Aya A. M. El-Bondkly Mohammed Abdel-Wahab Ayman A. Farghaly Ahmed Mohamed Ahmed El-Bondkly |
| author_facet | Mervat Morsy Abbas Ahmed El-Gendy Huda Ahmed Alghamdi Khaled G. Abdel-Wahhab Nabila S. Hassan Aya A. M. El-Bondkly Mohammed Abdel-Wahab Ayman A. Farghaly Ahmed Mohamed Ahmed El-Bondkly |
| author_sort | Mervat Morsy Abbas Ahmed El-Gendy |
| collection | DOAJ |
| description | Abstract Background Cancer is a significant global health issue due to its high incidence and mortality rates. In recent years, the relationship between the human microbiota and cancer has garnered attention across various medical fields. This includes research into the microbial communities that influence cancer development, tumor-associated microorganisms, and the interactions between the microbiome and tumor, collectively referred to as the oncobiome. Methods The negative effects of secondary metabolites extracted from selected multidrug-resistant Gram-negative bacteria within the cancer microbiota were evaluated. These effects included carcinogenicity, mutagenicity, hepatotoxicity, nephrotoxicity, and sperm deformities observed in albino rats after one month of oral ingestion of these microbial extracts. Results Our findings in the present investigation revealed that among the bacterial community derived from the microbiota, Gram-negative bacteria accounted for 74.87% the total microbiota (146 out of 195) and their spectrum including Escherichia sp. (n = 36, 24.66%) followed by Acinetobacter sp. (n = 34, 23.29%), Stenotrophomonas sp. (n = 29, 19.86%), Pseudomonas sp. (n = 26, 17.81%) and Serratia sp. (n = 21, 14.38%), as the most prevalent pathogens. All isolates derived from the cancer microbiome exhibited multidrug resistance to a large number of conventional therapies. Out of them Serratia sp. Esraa 1, Stenotrophomonas sp. Esraa 2, Acinetobacter sp. Esraa 3, Escherichia sp. Esraa 4 and Pseudomonas sp. Esraa 5 strains showed multidrug resistant profile against all antibiotic classes under study including penicillins, cephalosporins, carbapenems, fluoroquinolones, β-lactamase inhibitors combinations, folate synthesis pathway inhibitors, phosphonic, aminoglycosides, polymyxins, tetracyclines, macrolides, and chloramphenicol antibiotics. The adverse effects of oral ingestion of their metabolites were evaluated in albino rats. They induced pronounced carcinogenesis along with severe raise in the inflammatory cytokines, hepatotoxicity, nephrotoxicity, mutagenicity along with sperm deformities in treated animals. Moreover, all metabolites showed marked cytotoxicity against human normal cell lines; human mammary epithelial (MCF10A), human lung fibroblasts (WI38) and human dermal fibroblasts (HDFs). Conclusion These bacterial strains isolated from the cancer microbiome may play significant roles in inducing cancer, inflammation, mutagenesis, hepatotoxicity, nephrotoxicity, and sperm abnormalities, along with histopathological changes in the treated animal groups by orally administrated metabolites in compared to the untreated group. Graphical Abstract |
| format | Article |
| id | doaj-art-6f081225826349fd91f457396781c805 |
| institution | Kabale University |
| issn | 1750-9378 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Infectious Agents and Cancer |
| spelling | doaj-art-6f081225826349fd91f457396781c8052025-01-19T12:11:01ZengBMCInfectious Agents and Cancer1750-93782025-01-0120111810.1186/s13027-024-00634-yEvaluation of multidrug resistance in the Gram-negative microbiome of cancer patients and the adverse effects of their metabolites on albino rats and epithelial or fibroblasts cell linesMervat Morsy Abbas Ahmed El-Gendy0Huda Ahmed Alghamdi1Khaled G. Abdel-Wahhab2Nabila S. Hassan3Aya A. M. El-Bondkly4Mohammed Abdel-Wahab5Ayman A. Farghaly6Ahmed Mohamed Ahmed El-Bondkly7Chemistry of Natural and Microbial Products Department, National Research CentreDepartment of Biology, College of Sciences, King Khalid UniversityMedical Physiology Department, National Research CentrePathology Department, National Research CentreFaculty of Medicine, Cairo UniversityZoology Department, Faculty of Science, Al-Azhar UniversityGenetics and Cytology Department, National Research CentreGenetics and Cytology Department, National Research CentreAbstract Background Cancer is a significant global health issue due to its high incidence and mortality rates. In recent years, the relationship between the human microbiota and cancer has garnered attention across various medical fields. This includes research into the microbial communities that influence cancer development, tumor-associated microorganisms, and the interactions between the microbiome and tumor, collectively referred to as the oncobiome. Methods The negative effects of secondary metabolites extracted from selected multidrug-resistant Gram-negative bacteria within the cancer microbiota were evaluated. These effects included carcinogenicity, mutagenicity, hepatotoxicity, nephrotoxicity, and sperm deformities observed in albino rats after one month of oral ingestion of these microbial extracts. Results Our findings in the present investigation revealed that among the bacterial community derived from the microbiota, Gram-negative bacteria accounted for 74.87% the total microbiota (146 out of 195) and their spectrum including Escherichia sp. (n = 36, 24.66%) followed by Acinetobacter sp. (n = 34, 23.29%), Stenotrophomonas sp. (n = 29, 19.86%), Pseudomonas sp. (n = 26, 17.81%) and Serratia sp. (n = 21, 14.38%), as the most prevalent pathogens. All isolates derived from the cancer microbiome exhibited multidrug resistance to a large number of conventional therapies. Out of them Serratia sp. Esraa 1, Stenotrophomonas sp. Esraa 2, Acinetobacter sp. Esraa 3, Escherichia sp. Esraa 4 and Pseudomonas sp. Esraa 5 strains showed multidrug resistant profile against all antibiotic classes under study including penicillins, cephalosporins, carbapenems, fluoroquinolones, β-lactamase inhibitors combinations, folate synthesis pathway inhibitors, phosphonic, aminoglycosides, polymyxins, tetracyclines, macrolides, and chloramphenicol antibiotics. The adverse effects of oral ingestion of their metabolites were evaluated in albino rats. They induced pronounced carcinogenesis along with severe raise in the inflammatory cytokines, hepatotoxicity, nephrotoxicity, mutagenicity along with sperm deformities in treated animals. Moreover, all metabolites showed marked cytotoxicity against human normal cell lines; human mammary epithelial (MCF10A), human lung fibroblasts (WI38) and human dermal fibroblasts (HDFs). Conclusion These bacterial strains isolated from the cancer microbiome may play significant roles in inducing cancer, inflammation, mutagenesis, hepatotoxicity, nephrotoxicity, and sperm abnormalities, along with histopathological changes in the treated animal groups by orally administrated metabolites in compared to the untreated group. Graphical Abstracthttps://doi.org/10.1186/s13027-024-00634-yAntibiotic resistanceBacterial extractRatOral ingestionInflammatory cytokinesCarcinogenesis |
| spellingShingle | Mervat Morsy Abbas Ahmed El-Gendy Huda Ahmed Alghamdi Khaled G. Abdel-Wahhab Nabila S. Hassan Aya A. M. El-Bondkly Mohammed Abdel-Wahab Ayman A. Farghaly Ahmed Mohamed Ahmed El-Bondkly Evaluation of multidrug resistance in the Gram-negative microbiome of cancer patients and the adverse effects of their metabolites on albino rats and epithelial or fibroblasts cell lines Infectious Agents and Cancer Antibiotic resistance Bacterial extract Rat Oral ingestion Inflammatory cytokines Carcinogenesis |
| title | Evaluation of multidrug resistance in the Gram-negative microbiome of cancer patients and the adverse effects of their metabolites on albino rats and epithelial or fibroblasts cell lines |
| title_full | Evaluation of multidrug resistance in the Gram-negative microbiome of cancer patients and the adverse effects of their metabolites on albino rats and epithelial or fibroblasts cell lines |
| title_fullStr | Evaluation of multidrug resistance in the Gram-negative microbiome of cancer patients and the adverse effects of their metabolites on albino rats and epithelial or fibroblasts cell lines |
| title_full_unstemmed | Evaluation of multidrug resistance in the Gram-negative microbiome of cancer patients and the adverse effects of their metabolites on albino rats and epithelial or fibroblasts cell lines |
| title_short | Evaluation of multidrug resistance in the Gram-negative microbiome of cancer patients and the adverse effects of their metabolites on albino rats and epithelial or fibroblasts cell lines |
| title_sort | evaluation of multidrug resistance in the gram negative microbiome of cancer patients and the adverse effects of their metabolites on albino rats and epithelial or fibroblasts cell lines |
| topic | Antibiotic resistance Bacterial extract Rat Oral ingestion Inflammatory cytokines Carcinogenesis |
| url | https://doi.org/10.1186/s13027-024-00634-y |
| work_keys_str_mv | AT mervatmorsyabbasahmedelgendy evaluationofmultidrugresistanceinthegramnegativemicrobiomeofcancerpatientsandtheadverseeffectsoftheirmetabolitesonalbinoratsandepithelialorfibroblastscelllines AT hudaahmedalghamdi evaluationofmultidrugresistanceinthegramnegativemicrobiomeofcancerpatientsandtheadverseeffectsoftheirmetabolitesonalbinoratsandepithelialorfibroblastscelllines AT khaledgabdelwahhab evaluationofmultidrugresistanceinthegramnegativemicrobiomeofcancerpatientsandtheadverseeffectsoftheirmetabolitesonalbinoratsandepithelialorfibroblastscelllines AT nabilashassan evaluationofmultidrugresistanceinthegramnegativemicrobiomeofcancerpatientsandtheadverseeffectsoftheirmetabolitesonalbinoratsandepithelialorfibroblastscelllines AT ayaamelbondkly evaluationofmultidrugresistanceinthegramnegativemicrobiomeofcancerpatientsandtheadverseeffectsoftheirmetabolitesonalbinoratsandepithelialorfibroblastscelllines AT mohammedabdelwahab evaluationofmultidrugresistanceinthegramnegativemicrobiomeofcancerpatientsandtheadverseeffectsoftheirmetabolitesonalbinoratsandepithelialorfibroblastscelllines AT aymanafarghaly evaluationofmultidrugresistanceinthegramnegativemicrobiomeofcancerpatientsandtheadverseeffectsoftheirmetabolitesonalbinoratsandepithelialorfibroblastscelllines AT ahmedmohamedahmedelbondkly evaluationofmultidrugresistanceinthegramnegativemicrobiomeofcancerpatientsandtheadverseeffectsoftheirmetabolitesonalbinoratsandepithelialorfibroblastscelllines |