{"id":{"repo_id":"adelaide","oai_identifier":"oai:digital.library.adelaide.edu.au:2440/115411"},"canonical_url":"https://search.dev.ndltd.org/etd/adelaide/oai:digital.library.adelaide.edu.au:2440/115411","repository":{"repo_id":"adelaide","name":"University of Adelaide","base_url":"https://digital.library.adelaide.edu.au/server/oai/request"},"display":{"title":"Probiotic-derived factors as potential chemopreventive agents for intestinal mucositis and colon cancer","abstract":"Background: Colorectal cancer is one of the most deadly forms of cancer in humans. Current chemotherapeutic agents have limited efficacies for colon cancer treatment, and concurrently increase the risk of developing intestinal mucositis. Mucositis is the term for painful inflammation and ulcerating lesions of the mucous membranes lining the digestive tract. Intestinal mucositis is a common side-effect of cancer chemotherapy. To date, there are no satisfactory clinical treatments available to combat mucositis and colorectal cancer. Probiotics are live bacteria, some of which have been demonstrated to secrete bioactive factors capable of exerting beneficial effects; especially in the digestive system. The potential for probiotic-derived factors to combat intestinal mucositis and colon cancer has yet to be thoroughly investigated. In particular, the effects of factors derived from the same probiotic strain and cultured in different growth media have not been investigated in either setting. Objective: The project described in this thesis aimed to identify therapeutically effective bioactive formulations (probiotic-derived factors) capable of protecting the digestive tract from the devastating effects of mucositis and their potential for colon cancer management. The capacity for supernatants (SNs) from Escherichia coli Nissle 1917 (EcN) and Faecalibacterium prausnitzii (Fp) cultured under different growth conditions in the settings of mucositis and colorectal cancer models in vitro and in vivo were evaluated. Materials and Methods: EcN was grown in Luria-Bertani (LB) broth, tryptone soya broth (TSB), de Man Rogosa Sharpe (MRS) broth, and M17 broth supplemented with 10% (v/v) lactose solution (M17). Fp was grown anaerobically in M2 medium supplemented with 30% rumen fluid. Rat epithelial IEC-6, human colonic adenocarcinoma Caco-2 and T-84 cells were treated with DMEM (control), growth media alone (without factors) or SNs, in the presence and absence of 5-FU. Cell viability (MTT), reactive oxygen species (ROS), cell apoptosis and cell monolayer permeability were determined. Optimal SNs from the in vitro studies were further investigated in female dark agouti rats (101-146g). Animals received a daily oral gavage of EcN or Fp SNs (1mL) respectively from day 0 to 8. At day 5, rats were injected with either saline or 5- Fluorouracil (5-FU; 150 mg/kg). At kill, small intestinal tissues were collected for determination of myeloperoxidase (MPO) activity and histological assessment. Results and Conclusions: This thesis comprises the following 5 chapters: The potential mechanism of new nutraceuticals including probiotics, prebiotics and synbiotics, which may be suited to the treatment of intestinal mucositis and colon cancer, is extensively reviewed in Chapter1. Chapter 2 evaluated the capacity for SNs derived from EcN, cultured under different growth conditions, to prevent 5-Fluorouracil (5-FU)-induced intestinal epithelial cell damage. EcN SNs were able to reduce cell death, late apoptosis and enhance cell barrier function against 5-FU induced damage in IEC-6 cells, which indicated a potential role for EcN SN in the treatment of mucositis. Chapter 3 evaluated the effects of EcN SNs grown in different growth media on the viability of Caco-2 colon cancer cells in the presence and absence of 5-FU. EcN derived factors, especially grown in LB medium, were most effective at decreasing the viability of Caco-2 cells. This could indicate a potential role for this EcN SN in chemoprevention for colon cancer. Chapter 4 evaluated the effects of SNs derived from Fp on 5-FU treated intestinal cells (IEC-6, Caco-2 and T-84). The capacity of factors derived from Fp and EcN to prevent 5-FU induced damage in a rat model of mucositis was also investigated. Fp SN exerted toxic effects to colon cancer Caco-2 cells. However, in both Caco-2 and T84 cells, Fp SN partially prevented the decrease in cell barrier integrity caused by 5- FU administration. Furthermore, 5-FU-injected rats administered Fp SN or EcN SN partially prevented body weight loss and normalized water intake and faecal output compared with 5-FU controls. These results suggested a growth inhibitory mechanism of Fp SN action on transformed epithelial cells that could be mediated by effects on tight junctions. Factors derived from Fp SN and EcN SN could therefore have a role in reducing the severity of intestinal mucositis. Chapter 5 summarises and highlights the key findings from this thesis and indicates potential future directions. In particular, identification, isolation and characterization of the components of SNs require further investigation. The determination of the underlying mechanisms associated with the beneficial effects of specific probiotic derived factors would provide valuable information for the treatment of mucositis and colon cancer.","abstract_html":"Background: Colorectal cancer is one of the most deadly forms of cancer in humans. Current chemotherapeutic agents have limited efficacies for colon cancer treatment, and concurrently increase the risk of developing intestinal mucositis. Mucositis is the term for painful inflammation and ulcerating lesions of the mucous membranes lining the digestive tract. Intestinal mucositis is a common side-effect of cancer chemotherapy. To date, there are no satisfactory clinical treatments available to combat mucositis and colorectal cancer. Probiotics are live bacteria, some of which have been demonstrated to secrete bioactive factors capable of exerting beneficial effects; especially in the digestive system. The potential for probiotic-derived factors to combat intestinal mucositis and colon cancer has yet to be thoroughly investigated. In particular, the effects of factors derived from the same probiotic strain and cultured in different growth media have not been investigated in either setting. Objective: The project described in this thesis aimed to identify therapeutically effective bioactive formulations (probiotic-derived factors) capable of protecting the digestive tract from the devastating effects of mucositis and their potential for colon cancer management. The capacity for supernatants (SNs) from Escherichia coli Nissle 1917 (EcN) and Faecalibacterium prausnitzii (Fp) cultured under different growth conditions in the settings of mucositis and colorectal cancer models in vitro and in vivo were evaluated. Materials and Methods: EcN was grown in Luria-Bertani (LB) broth, tryptone soya broth (TSB), de Man Rogosa Sharpe (MRS) broth, and M17 broth supplemented with 10% (v/v) lactose solution (M17). Fp was grown anaerobically in M2 medium supplemented with 30% rumen fluid. Rat epithelial IEC-6, human colonic adenocarcinoma Caco-2 and T-84 cells were treated with DMEM (control), growth media alone (without factors) or SNs, in the presence and absence of 5-FU. Cell viability (MTT), reactive oxygen species (ROS), cell apoptosis and cell monolayer permeability were determined. Optimal SNs from the in vitro studies were further investigated in female dark agouti rats (101-146g). Animals received a daily oral gavage of EcN or Fp SNs (1mL) respectively from day 0 to 8. At day 5, rats were injected with either saline or 5- Fluorouracil (5-FU; 150 mg/kg). At kill, small intestinal tissues were collected for determination of myeloperoxidase (MPO) activity and histological assessment. Results and Conclusions: This thesis comprises the following 5 chapters: The potential mechanism of new nutraceuticals including probiotics, prebiotics and synbiotics, which may be suited to the treatment of intestinal mucositis and colon cancer, is extensively reviewed in Chapter1. Chapter 2 evaluated the capacity for SNs derived from EcN, cultured under different growth conditions, to prevent 5-Fluorouracil (5-FU)-induced intestinal epithelial cell damage. EcN SNs were able to reduce cell death, late apoptosis and enhance cell barrier function against 5-FU induced damage in IEC-6 cells, which indicated a potential role for EcN SN in the treatment of mucositis. Chapter 3 evaluated the effects of EcN SNs grown in different growth media on the viability of Caco-2 colon cancer cells in the presence and absence of 5-FU. EcN derived factors, especially grown in LB medium, were most effective at decreasing the viability of Caco-2 cells. This could indicate a potential role for this EcN SN in chemoprevention for colon cancer. Chapter 4 evaluated the effects of SNs derived from Fp on 5-FU treated intestinal cells (IEC-6, Caco-2 and T-84). The capacity of factors derived from Fp and EcN to prevent 5-FU induced damage in a rat model of mucositis was also investigated. Fp SN exerted toxic effects to colon cancer Caco-2 cells. However, in both Caco-2 and T84 cells, Fp SN partially prevented the decrease in cell barrier integrity caused by 5- FU administration. Furthermore, 5-FU-injected rats administered Fp SN or EcN SN partially prevented body weight loss and normalized water intake and faecal output compared with 5-FU controls. These results suggested a growth inhibitory mechanism of Fp SN action on transformed epithelial cells that could be mediated by effects on tight junctions. Factors derived from Fp SN and EcN SN could therefore have a role in reducing the severity of intestinal mucositis. Chapter 5 summarises and highlights the key findings from this thesis and indicates potential future directions. In particular, identification, isolation and characterization of the components of SNs require further investigation. The determination of the underlying mechanisms associated with the beneficial effects of specific probiotic derived factors would provide valuable information for the treatment of mucositis and colon cancer.","abstract_has_math":false,"creators":["Wang, Hanru"],"institution":null,"degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":["Howarth, Gordon Stanley","Bastian, Sue"],"committee_chairs":[],"committee_members":[],"year":2016,"date_issued":"2016","date_published":"2016","updated_at":"2026-07-24T00:50:56Z","subjects":["cell biology","mucositis","colon cancer","animal model","Research by Publication"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier.doi","label":"DOI","values":["10.25909/5bd0f56ac8d48"],"render_values":[{"text":"10.25909/5bd0f56ac8d48","href":"https://doi.org/10.25909/5bd0f56ac8d48","code":true}]}]},"links":{"outbound_url":"http://hdl.handle.net/2440/115411","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Howarth, Gordon Stanley","Bastian, Sue"]},{"key":"dc:creator","label":"Author","values":["Wang, Hanru"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.issued","label":"Date","values":["2016"]},{"key":"dc:type","label":"Dc Type","values":["Theses"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["cell biology","mucositis","colon cancer","animal model","Research by Publication"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.doi","label":"DOI","values":["10.25909/5bd0f56ac8d48"]},{"key":"dc:identifier.uri","label":"Identifier URI","values":["http://hdl.handle.net/2440/115411"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Background: Colorectal cancer is one of the most deadly forms of cancer in humans. Current chemotherapeutic agents have limited efficacies for colon cancer treatment, and concurrently increase the risk of developing intestinal mucositis. Mucositis is the term for painful inflammation and ulcerating lesions of the mucous membranes lining the digestive tract. Intestinal mucositis is a common side-effect of cancer chemotherapy. To date, there are no satisfactory clinical treatments available to combat mucositis and colorectal cancer. Probiotics are live bacteria, some of which have been demonstrated to secrete bioactive factors capable of exerting beneficial effects; especially in the digestive system. The potential for probiotic-derived factors to combat intestinal mucositis and colon cancer has yet to be thoroughly investigated. In particular, the effects of factors derived from the same probiotic strain and cultured in different growth media have not been investigated in either setting. Objective: The project described in this thesis aimed to identify therapeutically effective bioactive formulations (probiotic-derived factors) capable of protecting the digestive tract from the devastating effects of mucositis and their potential for colon cancer management. The capacity for supernatants (SNs) from Escherichia coli Nissle 1917 (EcN) and Faecalibacterium prausnitzii (Fp) cultured under different growth conditions in the settings of mucositis and colorectal cancer models in vitro and in vivo were evaluated. Materials and Methods: EcN was grown in Luria-Bertani (LB) broth, tryptone soya broth (TSB), de Man Rogosa Sharpe (MRS) broth, and M17 broth supplemented with 10% (v/v) lactose solution (M17). Fp was grown anaerobically in M2 medium supplemented with 30% rumen fluid. Rat epithelial IEC-6, human colonic adenocarcinoma Caco-2 and T-84 cells were treated with DMEM (control), growth media alone (without factors) or SNs, in the presence and absence of 5-FU. Cell viability (MTT), reactive oxygen species (ROS), cell apoptosis and cell monolayer permeability were determined. Optimal SNs from the in vitro studies were further investigated in female dark agouti rats (101-146g). Animals received a daily oral gavage of EcN or Fp SNs (1mL) respectively from day 0 to 8. At day 5, rats were injected with either saline or 5- Fluorouracil (5-FU; 150 mg/kg). At kill, small intestinal tissues were collected for determination of myeloperoxidase (MPO) activity and histological assessment. Results and Conclusions: This thesis comprises the following 5 chapters: The potential mechanism of new nutraceuticals including probiotics, prebiotics and synbiotics, which may be suited to the treatment of intestinal mucositis and colon cancer, is extensively reviewed in Chapter1. Chapter 2 evaluated the capacity for SNs derived from EcN, cultured under different growth conditions, to prevent 5-Fluorouracil (5-FU)-induced intestinal epithelial cell damage. EcN SNs were able to reduce cell death, late apoptosis and enhance cell barrier function against 5-FU induced damage in IEC-6 cells, which indicated a potential role for EcN SN in the treatment of mucositis. Chapter 3 evaluated the effects of EcN SNs grown in different growth media on the viability of Caco-2 colon cancer cells in the presence and absence of 5-FU. EcN derived factors, especially grown in LB medium, were most effective at decreasing the viability of Caco-2 cells. This could indicate a potential role for this EcN SN in chemoprevention for colon cancer. Chapter 4 evaluated the effects of SNs derived from Fp on 5-FU treated intestinal cells (IEC-6, Caco-2 and T-84). The capacity of factors derived from Fp and EcN to prevent 5-FU induced damage in a rat model of mucositis was also investigated. Fp SN exerted toxic effects to colon cancer Caco-2 cells. However, in both Caco-2 and T84 cells, Fp SN partially prevented the decrease in cell barrier integrity caused by 5- FU administration. Furthermore, 5-FU-injected rats administered Fp SN or EcN SN partially prevented body weight loss and normalized water intake and faecal output compared with 5-FU controls. These results suggested a growth inhibitory mechanism of Fp SN action on transformed epithelial cells that could be mediated by effects on tight junctions. Factors derived from Fp SN and EcN SN could therefore have a role in reducing the severity of intestinal mucositis. Chapter 5 summarises and highlights the key findings from this thesis and indicates potential future directions. In particular, identification, isolation and characterization of the components of SNs require further investigation. The determination of the underlying mechanisms associated with the beneficial effects of specific probiotic derived factors would provide valuable information for the treatment of mucositis and colon cancer."]},{"key":"dc:title","label":"Title","values":["Probiotic-derived factors as potential chemopreventive agents for intestinal mucositis and colon cancer"]}]}],"canonical_facts":{"dc:contributor.advisor":["Howarth, Gordon Stanley","Bastian, Sue"],"dc:creator":["Wang, Hanru"],"dc:date.issued":["2016"],"dc:description.abstract":["Background: Colorectal cancer is one of the most deadly forms of cancer in humans. Current chemotherapeutic agents have limited efficacies for colon cancer treatment, and concurrently increase the risk of developing intestinal mucositis. Mucositis is the term for painful inflammation and ulcerating lesions of the mucous membranes lining the digestive tract. Intestinal mucositis is a common side-effect of cancer chemotherapy. To date, there are no satisfactory clinical treatments available to combat mucositis and colorectal cancer. Probiotics are live bacteria, some of which have been demonstrated to secrete bioactive factors capable of exerting beneficial effects; especially in the digestive system. The potential for probiotic-derived factors to combat intestinal mucositis and colon cancer has yet to be thoroughly investigated. In particular, the effects of factors derived from the same probiotic strain and cultured in different growth media have not been investigated in either setting. Objective: The project described in this thesis aimed to identify therapeutically effective bioactive formulations (probiotic-derived factors) capable of protecting the digestive tract from the devastating effects of mucositis and their potential for colon cancer management. The capacity for supernatants (SNs) from Escherichia coli Nissle 1917 (EcN) and Faecalibacterium prausnitzii (Fp) cultured under different growth conditions in the settings of mucositis and colorectal cancer models in vitro and in vivo were evaluated. Materials and Methods: EcN was grown in Luria-Bertani (LB) broth, tryptone soya broth (TSB), de Man Rogosa Sharpe (MRS) broth, and M17 broth supplemented with 10% (v/v) lactose solution (M17). Fp was grown anaerobically in M2 medium supplemented with 30% rumen fluid. Rat epithelial IEC-6, human colonic adenocarcinoma Caco-2 and T-84 cells were treated with DMEM (control), growth media alone (without factors) or SNs, in the presence and absence of 5-FU. Cell viability (MTT), reactive oxygen species (ROS), cell apoptosis and cell monolayer permeability were determined. Optimal SNs from the in vitro studies were further investigated in female dark agouti rats (101-146g). Animals received a daily oral gavage of EcN or Fp SNs (1mL) respectively from day 0 to 8. At day 5, rats were injected with either saline or 5- Fluorouracil (5-FU; 150 mg/kg). At kill, small intestinal tissues were collected for determination of myeloperoxidase (MPO) activity and histological assessment. Results and Conclusions: This thesis comprises the following 5 chapters: The potential mechanism of new nutraceuticals including probiotics, prebiotics and synbiotics, which may be suited to the treatment of intestinal mucositis and colon cancer, is extensively reviewed in Chapter1. Chapter 2 evaluated the capacity for SNs derived from EcN, cultured under different growth conditions, to prevent 5-Fluorouracil (5-FU)-induced intestinal epithelial cell damage. EcN SNs were able to reduce cell death, late apoptosis and enhance cell barrier function against 5-FU induced damage in IEC-6 cells, which indicated a potential role for EcN SN in the treatment of mucositis. Chapter 3 evaluated the effects of EcN SNs grown in different growth media on the viability of Caco-2 colon cancer cells in the presence and absence of 5-FU. EcN derived factors, especially grown in LB medium, were most effective at decreasing the viability of Caco-2 cells. This could indicate a potential role for this EcN SN in chemoprevention for colon cancer. Chapter 4 evaluated the effects of SNs derived from Fp on 5-FU treated intestinal cells (IEC-6, Caco-2 and T-84). The capacity of factors derived from Fp and EcN to prevent 5-FU induced damage in a rat model of mucositis was also investigated. Fp SN exerted toxic effects to colon cancer Caco-2 cells. However, in both Caco-2 and T84 cells, Fp SN partially prevented the decrease in cell barrier integrity caused by 5- FU administration. Furthermore, 5-FU-injected rats administered Fp SN or EcN SN partially prevented body weight loss and normalized water intake and faecal output compared with 5-FU controls. These results suggested a growth inhibitory mechanism of Fp SN action on transformed epithelial cells that could be mediated by effects on tight junctions. Factors derived from Fp SN and EcN SN could therefore have a role in reducing the severity of intestinal mucositis. Chapter 5 summarises and highlights the key findings from this thesis and indicates potential future directions. In particular, identification, isolation and characterization of the components of SNs require further investigation. The determination of the underlying mechanisms associated with the beneficial effects of specific probiotic derived factors would provide valuable information for the treatment of mucositis and colon cancer."],"dc:identifier.doi":["10.25909/5bd0f56ac8d48"],"dc:identifier.uri":["http://hdl.handle.net/2440/115411"],"dc:subject":["cell biology","mucositis","colon cancer","animal model","Research by Publication"],"dc:title":["Probiotic-derived factors as potential chemopreventive agents for intestinal mucositis and colon cancer"],"dc:type":["Theses"]},"updated_at":"2026-07-24T00:50:56Z"}