Impact of intestinal bacteria on the anatomy and physiology of the intestinal tract in the PRM/Alf mouse model
Zusammenfassung der Projektergebnisse
Bacteria play an important role in the maturation of the gastrointestinal tract. They influence intestinal epithelial maturation, development of the lamina propria and crypt depth. However, the underlying mode of action is largely unknown. The PRM/Alf mouse offered a unique opportunity to gain new insights into these mechanisms. These mice develop a gut which is one third longer than that of control strains. A comparison of germfree and conventional PRM/Alf mice indicated an important role of the intestinal microbiota in this elongation. To identify the bacterial factors involved, our French project partners colonized germfree PRM/Alf mice with a complex microbiota obtained from conventional PRM/Alf and C3H mice. The intestinal length of PRM/Alf mice harbouring the C3H microbiota was 19 % reduced compared to the PRM/Alf mice harbouring PRM/Alf microbiota indicating a role of the PRM/Alf microbiota on gut lengthening. We investigated whether polyamines possibly serve as bacterial trophic factors. The N-acetylspermine concentration in PRM/Alf mice harbouring the PRM/Alf microbiota was 7.5-fold increased to PRM/Alf mice with the C3H microbiota. However, it remains unclear whether this polyamine contributes to gut elongation. To identify bacterial species contributing to gut elongation, we colonized germfree PRM/Alf and C3H mice with a simplified human microbiota (SIHUMI). The intestinal length was 37 % increased in PRM/Alf mice compared to C3H mice. However, the intestinal length of PRM/Alf mice associated with SIHUMI was 11 % and 18 % reduced compared to germfree and conventional mice, respectively, indicating that the simplified human microbiota contributed to gut shortening. Possible bacterial trophic factors such as SCFA and polyamines were decreased in PRM/Alf but not in C3H mice (both associated with SIHUMI). Anaerostipes caccae was also decreased in PRM/Alf mice, but no bacterial factors contributing to gut elongation were identified. To elucidate the role of polyamines as one bacterial factor possibly involved in gut growth, we colonized germfree C3H mice with two microbiotas producing different polyamine concentrations. One group was colonized with the SIHUMI. The other group was associated with SIHUMI + Fusobacterium varium (SIHUMI + Fv), which is known to produce high amounts of polyamines. SIHUMI + Fv mice had a 2-fold higher cecal and colonic polyamine concentration compared to SIHUMI, which was mainly due to putrescine. Despite the increased polyamine concentration, no differences were observed in colonic length. Crypt depth, thickness of mucosa, submucosa, epithelial layer and muscularis externa in cecum and colon was unchanged. The same was true for proliferation and apoptosis. These findings indicate that high putrescine concentrations have no impact on gut morphology in our model. However, it is conceivable that the putrescine concentration in SIHUMI mice is sufficient for gut development so that putrescine concentrations exceeding the physiological need have no additional effects.
Projektbezogene Publikationen (Auswahl)
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(2010) Search for intestinotrophic factors in the intestinal microbiota of the PRM/Alf mouse, an animal model of intestinal lengthening. International Scientific Conference on Gastrointestinal Microbial Ecology, Kosice, Slovakia
Krupova, Z., Bernex, F., Blaut, M., Slezak, K., Loh, G., Martin, P., Doré, J., Rabot, S., Descamps, A., Panthier, J.J., Jaubert, J., Mater, D., Bellier, S.
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(2010) The PRM/Alf mouse: a study model of the interrelationships between the Microbiota, the Nutrients and the Intestine (MiNI Mouse). USA/IRELAND Functional Food Conference, Corck, Ireland
Bellier, S., Krupova, Z., Bernex, F., Blaut, M., Slezak, K., Martin, P., Boumahrou, N., Doré, J., Rabot, S., Jaubert, J., Panthier, J.J., Mater, D.
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(2011) Bacterial polyamines have no impact on gut anatomy of mice. Nugoweek 2011, Wageningen, Netherlands
Slezak, K., Hankse, L., Loh, G., Blaut, M.
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(2011) Impact of gut microbiota on gut elongation in the PRM/Alf mouse model. 11th European Nutrition Conference, Madrid, Spain
Slezak, K., Krupova, Z., Hanske, L., Descamps, A., Rabot, S., Loh, G., Bellier, S., Blaut, M.
