PhD defence by Pi Westi Bondegaard

Principal supervisor

• Professor Tine Rask Licht

Co-supervisors

• Senior Scientist Martin Iain Bahl
• Senior Scientist Martin Steen Mortensen

Examiners

• Professor Lisbeth Truelstrup Hansen, National Food Institute DTU
• Professor Anette Müllertz, University of Copenhagen
• Professor Michiel Kleerebezem, Wageningen University

Chairperson at defence

• Associate professor Martin Frederik Laursen

Resume

Ulcerative colitis (UC) is a chronic intestinal disease resulting in impaired quality of life for the affected patients. It is an increasing problem worldwide, but current therapeutic strategies are associated with unresponsiveness and side effects in many patients. Alternative treatment methods are intensively investigated, and some candidates of probiotic bacteria and antioxidants show promising effects. Protection of the agents and local intestinal administration to the site of disease can be provided by novel delivery systems and these are suggested to enhance the beneficial outcome further. Therefore, the present PhD study aimed to evaluate the use of micrometre-sized microcontainers for alleviation of UC by delivery of the probiotic bacteria, E. coli Nissle and the antioxidant, vitamin C – both holding promise as alternative treatment strategies.

Microcontainer delivery of the probiotic, E. coli Nissle was compared to conventional oral delivery strategies by evaluating the colonisation and competition ability against two UC-associated E. coli strains in streptomycin-treated mice. No beneficial effects of microcontainer delivery were shown, and the probiotic and disease-associated strains co-colonised.

Addtionally, the effect of microcontainer-based delivery of the antioxidant, vitamin C was assessed in a colitis mouse model. Delivery within peanut butter with or without microcontainers partially alleviated disease symptoms, whereas a high dose vitamin C in drinking water did not have any positive effects. The colitis-associated microbial dysbiosis was not affected by the antioxidant delivery. These results emphasise the importance of delivery strategy for vitamin C and encourage to further investigation of the relevance for human consumption.

In conclusion, microcontainers can deliver UC-relevant candidates of both probiotics and antioxidants to the intestine. However, within the studies of this PhD, no beneficial effects were assigned to this delivery system compared to simple oral administration. Future development of other strategies for delivery of probiotics and antioxidants are thus needed to improve alleviation of UC.