Use of Germ-Free Animal Models in Microbiota-Related Research

Al-Asmakh, Maha; Zadjali, Fahad

doi:10.4014/jmb.1501.01039

Cited by 200 publications

(130 citation statements)

References 29 publications

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“…paracasei and E. coli in lipid absorption and secretion by enterocytes, and since the gastrointestinal tract of GF mice is considered immature and potentially associated with alterations of nutrient absorption (21), conventional specific-pathogen-free (SPF) mice were administered a gut microbiota-depleting treatment (22) to allow efficient L. paracasei and E.…”

Section: Resultsmentioning

confidence: 99%

Disentangling Host-Microbiota Regulation of Lipid Secretion by Enterocytes: Insights from Commensals Lactobacillus paracasei and Escherichia coli

Tazi

Araújo

Mulet

et al. 2018

mBio

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The specific contribution of each bacterial species within a complex microbiota to the regulation of host lipid metabolism remains largely unknown. Using two model commensal microorganisms, L. paracasei and E. coli, we demonstrated that both bacterial species impacted host lipid metabolism in a diet-dependent manner and, notably, that L. paracasei-colonized mice but not E. coli-colonized mice resisted high-fat-diet-induced body weight gain. In addition, we set up cellular models of fatty acid absorption and secretion by enterocytes cocultured with bacteria and showed that, in vitro, both L. paracasei and E. coli inhibited lipid secretion, through increased intracellular fat storage and enhanced lipid catabolism, respectively.

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Section: Resultsmentioning

confidence: 99%

Disentangling Host-Microbiota Regulation of Lipid Secretion by Enterocytes: Insights from Commensals Lactobacillus paracasei and Escherichia coli

Tazi

Araújo

Mulet

et al. 2018

mBio

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“…However, whether the accumulation of SFB or other specific bacteria taxa in class Clostridia alters epithelial cell turnover and barrier function-enhancing sensitivity to epithelial injury-awaits further investigation with singlespecies colonization of germ-free mice. It should be also noted that investigators should be cautious with the interpretation of the effects in germ-free mice as they are known to have abnormalities in intestinal development and mucosal immune system (71)(72)(73)(74).…”

Section: Discussionmentioning

confidence: 99%

Intestinal microbiota contributes to colonic epithelial changes in simulated microgravity mouse model

Shi

Wang

et al. 2017

FASEB j.

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Exposure to microgravity leads to alterations in multiple systems, but microgravity-related changes in the gastrointestinal tract and its clinical significance have not been well studied. We used the hindlimb unloading (HU) mouse model to simulate a microgravity condition and investigated the changes in intestinal microbiota and colonic epithelial cells. Compared with ground-based controls (Ctrls), HU affected fecal microbiota composition with a profile that was characterized by the expansion of Firmicutes and decrease of Bacteroidetes. The colon epithelium of HU mice showed decreased goblet cell numbers, reduced epithelial cell turnover, and decreased expression of genes that are involved in defense and inflammatory responses. As a result, increased susceptibility to dextran sulfate sodium-induced epithelial injury was observed in HU mice. Cohousing of Ctrl mice with HU mice resulted in HUlike epithelial changes in Ctrl mice. Transplantation of feces from Ctrl to HU mice alleviated these epithelial changes in HU mice. Results indicate that HU changes intestinal microbiota, which leads to altered colonic epithelial cell homeostasis, impaired barrier function, and increased susceptibility to colitis. We further demonstrate that alteration in gastrointestinal motility may contribute to HU-associated dysbiosis. These animal results emphasize the necessity of evaluating astronauts' intestinal homeostasis during distant space travel.-Shi, J., Wang, Y., He, J., Li, P., Jin, R., Wang, K., Xu, X., Hao, J., Zhang, Y., Liu, H., Chen, X., Wu, H., Ge, Q. Intestinal microbiota contributes to colonic epithelial changes in simulated microgravity mouse model. FASEB J. 31, 3695-3709 (2017 Exposure to microgravity leads to alterations, such as bone demineralization, muscle atrophy, cardiovascular deconditioning, and immune dysfunction, in multiple systems (1). Limited reports also suggest that spaceflight and microgravity affect the integrity of intestinal epithelium. For instance, reduced length of villi and depth of crypts was found in rats that were flown on 12-d Cosmos 2044 and Foton M3 missions (2, 3), and decreased mucin production of intestinal epithelial cells was shown in rats that were flown on the 19.5-d Cosmos 605 mission (4). Colonic TGF-b expression was altered in mice aboard the 13-d STS-135 or 91-d International Space Station missions (5, 6). Using a well-accepted, ground-based spaceflight analog, the hindlimb unloading (HU) mouse model (7) found that simulated microgravity resulted in a transient increase in intestinal permeability, which is characterized by the elevation of circulating LPS and the activation of the innate immune system. The clinical significance and mechanism of these epithelial changes are not clear; however, Chopra et al. (8) reported that HU mice that were infected with Salmonella enterica serovar typhimurium had a 100-fold decrease in LD 50 compared with normal-gravity control (Ctrl) mice. This indicates that microgravity-induced intestinal epithelial changes may exacerbate bacte...

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“…An additional validation of the SPF hygiene level can be achieved by applying special micro-isolator cages such as filter top cages and individual ventilated cages (IVCs). Compared to conventional animals all these measures lead to an increased life expectation and an enhanced rearing power [7, 8]. …”

Section: Preconditions For Experimental Application Of Germfree Animamentioning

confidence: 99%

“…The animal facilities focusing on breeding and handling of animals under sterile conditions have therefore to be equipped in minimum with sterilization of cage materials in autoclaves and sterile filtration of the air supplies [7, 8]. …”

Section: Preconditions For Experimental Application Of Germfree Animamentioning

confidence: 99%

Dissecting the interplay between intestinal microbiota and host immunity in health and disease: Lessons learned from germfree and gnotobiotic animal models

Fiebiger

Bereswill

Heimesaat

2016

EuJMI

123

121

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This review elaborates the development of germfree and gnotobiotic animal models and their application in the scientific field to unravel mechanisms underlying host–microbe interactions and distinct diseases. Strictly germfree animals are raised in isolators and not colonized by any organism at all. The germfree state is continuously maintained by birth, raising, housing and breeding under strict sterile conditions. However, isolator raised germfree mice are exposed to a stressful environment and exert an underdeveloped immune system. To circumvent these physiological disadvantages depletion of the bacterial microbiota in conventionally raised and housed mice by antibiotic treatment has become an alternative approach. While fungi and parasites are not affected by antibiosis, the bacterial microbiota in these “secondary abiotic mice” have been shown to be virtually eradicated. Recolonization of isolator raised germfree animals or secondary abiotic mice results in a gnotobiotic state. Both, germfree and gnotobiotic mice have been successfully used to investigate biological functions of the conventional microbiota in health and disease. Particularly for the development of novel clinical applications germfree mice are widely used tools, as summarized in this review further focusing on the modulation of bacterial microbiota in laboratory mice to better mimic conditions in the human host.

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Use of Germ-Free Animal Models in Microbiota-Related Research

Cited by 200 publications

References 29 publications

Disentangling Host-Microbiota Regulation of Lipid Secretion by Enterocytes: Insights from Commensals Lactobacillus paracasei and Escherichia coli

Disentangling Host-Microbiota Regulation of Lipid Secretion by Enterocytes: Insights from Commensals Lactobacillus paracasei and Escherichia coli

Intestinal microbiota contributes to colonic epithelial changes in simulated microgravity mouse model

Dissecting the interplay between intestinal microbiota and host immunity in health and disease: Lessons learned from germfree and gnotobiotic animal models

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