Germ-free mice are markedly resistant to lethal radiation enteritis, with 0% mortality at 40 days compared to 52% mortality within 7 days in conventionally raised mice after 16 Gy of irradiation.
Does the presence of microbiota regulate intestinal radiosensitivity and radiation-induced apoptosis in mice?
The gut microbiota enhances intestinal radiosensitivity and radiation-induced apoptosis of endothelial cells and lymphocytes, a process mediated by the suppression of fasting-induced adipose factor (Fiaf).
Tasa de eventos absoluta: 0% vs 52%
valor p: p=<0.001
We describe a method for treating germ-free (GF) mice with gamma-irradiation and transplanting them with normal or genetically manipulated bone marrow while maintaining their GF status. This approach revealed that GF mice are markedly resistant to lethal radiation enteritis. Furthermore, administering lethal doses of total body irradiation to GF mice produces markedly fewer apoptotic endothelial cells and lymphocytes in the mesenchymal cores of their small intestinal villi, compared with conventionally raised animals that have acquired a microbiota from birth. Analysis of GF and conventionally raised Rag1-/- mice disclosed that mature lymphocytes are not required for the development of lethal radiation enteritis or the microbiota-associated enhancement of endothelial radiosensitivity. Studies of gnotobiotic knockout mice that lack fasting-induced adipose factor (Fiaf), a fibrinogen/angiopoietin-like protein normally secreted from the small intestinal villus epithelium and suppressed by the microbiota, showed that Fiaf deficiency results in loss of resistance of villus endothelial and lymphocyte populations to radiation-induced apoptosis. Together, these findings provide insights about the cellular and molecular targets involved in microbial regulation of intestinal radiosensitivity.
Crawford et al. (Mon,) conducted a other in Radiation enteritis. Germ-free status (absence of gut microbiota) vs. Conventionally raised (CONV-R) or conventionalized (CONV-D) status was evaluated on Mortality after 16 Gy of total body irradiation and bone marrow transplantation (p=<0.001). Germ-free mice are markedly resistant to lethal radiation enteritis, with 0% mortality at 40 days compared to 52% mortality within 7 days in conventionally raised mice after 16 Gy of irradiation.
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