Effects of the Germfree State on Responses of Mice to Whole-Body Irradiation

McLaughlin, Mary; Dacquisto, Michael P.; Jacobus, David P.; Horowitz, Richard E.

doi:10.2307/3571614

Cited by 73 publications

(41 citation statements)

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“…Alternatively, it is well known that the indigenous microbiota stimulates the epithelial intestinal renewal, increasing cell sensitivity and/or the affinity of the intestinal cells to the drug and increasing its absorption. Indeed, the intestinal epithelial renewal rate is lower in GF animals when compared to CV mice (McLaughlin et al, 1964).…”

Section: Discussionmentioning

confidence: 99%

Evaluation of mucositis induced by irinotecan after microbial colonization in germ-free mice

et al. 2015

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Mucositis is one of the most debilitating side effects of chemotherapy and some previous studies suggest a role for indigenous microbiota in the course of this pathology. Therefore, the aim of our study was to evaluate the differences in phenotype between germ-free (GF) and conventional (CV) mice, and the role of b-glucuronidase-producing bacteria in the development of irinotecan treatment in a murine model. After mucositis induction, CV mice showed a significant increase in all inflammatory parameters when compared to GF mice. CV animals also showed more lesions of the intestinal epithelium, coherent with their higher intestinal permeability. The conventionalization of GF animals reversed their phenotype to that found in CV mice. In addition, gnotobiotic mice monoassociated with an Escherichia coli strain producing b-glucuronidase showed an increased permeability when compared to gnotobiotic mice monoassociated with an E. coli strain deleted for the gene encoding b-glucuronidase, but these did not show any differences in the influx of neutrophils, eosinophils or histological characteristics. Our data confirmed that components of the gut microbiota are involved in the signs of mucositis. Nevertheless, other mechanisms than this enzyme are involved in the irinotecan treatment, since the monoassociation was not able to restore the entire phenotype observed in the CV animals with irinotecan treatment in our murine model.

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Section: Discussionmentioning

confidence: 99%

Evaluation of mucositis induced by irinotecan after microbial colonization in germ-free mice

et al. 2015

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“…Large radiation doses (>8 Gy) can cause detrimental effects such as direct mucosal toxicity, delayed gastric emptying and secretion, and villous shortening [7, 12]. Some data suggests that radiation exposure can affect the intestinal microbiota, and the presence and composition of these commensal bacterial groups has an effect on radiation induced-lethality [13–15]. Furthermore, we have reported that consumption of a diet with elevated dietary iron, by itself and in combination with low LET radiation, can alter the concentration of fecal SCFA [16], suggesting alterations to the composition of the intestinal microbiota or a functional change in microbial metabolism.…”

Section: Introductionmentioning

confidence: 99%

Space Environmental Factor Impacts upon Murine Colon Microbiota and Mucosal Homeostasis

et al. 2015

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Astronaut intestinal health may be impacted by microgravity, radiation, and diet. The aim of this study was to characterize how high and low linear energy transfer (LET) radiation, microgravity, and elevated dietary iron affect colon microbiota (determined by 16S rDNA pyrosequencing) and colon function. Three independent experiments were conducted to achieve these goals: 1) fractionated low LET γ radiation (137Cs, 3 Gy, RAD), high Fe diet (IRON) (650 mg/kg diet), and a combination of low LET γ radiation and high Fe diet (IRON+RAD) in male Sprague-Dawley rats; 2) high LET 38Si particle exposure (0.050 Gy), 1/6 G partial weight bearing (PWB), and a combination of high LET38Si particle exposure and PWB in female BalbC/ByJ mice; and 3) 13 d spaceflight in female C57BL/6 mice. Low LET radiation, IRON and spaceflight increased Bacteroidetes and decreased Firmicutes. RAD and IRON+RAD increased Lactobacillales and lowered Clostridiales compared to the control (CON) and IRON treatments. Low LET radiation, IRON, and spaceflight did not significantly affect diversity or richness, or elevate pathogenic genera. Spaceflight increased Clostridiales and decreased Lactobacillales, and similar trends were observed in the experiment using a ground-based model of microgravity, suggesting altered gravity may affect colonic microbiota. Although we noted no differences in colon epithelial injury or inflammation, spaceflight elevated TGFβ gene expression. Microbiota and mucosal characterization in these models is a first step in understanding the impact of the space environment on intestinal health.

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“…First, the minimum dose required to induce 50% mortality is higher in GF mice (20). Second, after receiving lethal doses of total body irradiation (TBI), GF animals survive longer than their CONV-R counterparts (20)(21)(22). Third, the minimum TBI dose that produces histological evidence of radiation enteritis (mucosal atrophy, mesenchymal inflammation, and fibrosis) is higher in GF mice, compared with animals with a microbiota (21).…”

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confidence: 99%

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confidence: 99%

Microbial regulation of intestinal radiosensitivity

Crawford

Gordon

2005

Proc. Natl. Acad. Sci. U.S.A.

204

166

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We describe a method for treating germ-free (GF) mice with ␥-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 fibrinogen͞angio-poietin-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.endothelial cell apoptosis ͉ fasting-induced adipose factor ͉ gnotobiotic knockout and radiation chimeric mice ͉ gut microbiota ͉ radiation enteritis

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Effects of the Germfree State on Responses of Mice to Whole-Body Irradiation

Cited by 73 publications

References 0 publications

Evaluation of mucositis induced by irinotecan after microbial colonization in germ-free mice

Evaluation of mucositis induced by irinotecan after microbial colonization in germ-free mice

Space Environmental Factor Impacts upon Murine Colon Microbiota and Mucosal Homeostasis

Microbial regulation of intestinal radiosensitivity

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