Dataset Information

Establishment of murine gut microbiota in gnotobiotic mice.

ABSTRACT: Determining whether associations between gut microbiota characteristics and host physiology represent causal relationships is a fundamental challenge for microbiome research. We report a detailed investigation of microbiome assembly in C57BL/6 germ-free mice across a period of 70 days and compare the effects of single and multiple rounds of gavage, using both native and antibiotic-disrupted murine donor material. Recipients of the native microbiota did not achieve compositional stability until day 28 and persistent differences to donor microbiota remained until day 70. Performing multiple rounds of gavage significantly increased the cumulative number of detected taxa (mean increase: 10.4%) and compositional similarity to donor, and significantly reduced within-group variance (p < 0.05). Multiple rounds of gavage with antibiotic-disrupted microbiota provided no substantial benefit in relation to compositional similarity to donor or within-group variance. The process of donor microbiota establishment in recipient animals is necessary before experimentation commences and is considerably influenced by donor microbiota characteristics.

SUBMITTER: Choo JM

PROVIDER: S-EPMC7840467 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Establishment of murine gut microbiota in gnotobiotic mice.

Choo Jocelyn M JM Rogers Geraint B GB

iScience 20210112 2

Determining whether associations between gut microbiota characteristics and host physiology represent causal relationships is a fundamental challenge for microbiome research. We report a detailed investigation of microbiome assembly in C57BL/6 germ-free mice across a period of 70 days and compare the effects of single and multiple rounds of gavage, using both native and antibiotic-disrupted murine donor material. Recipients of the native microbiota did not achieve compositional stability until d ...[more]

PMID: 33537656

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Project description:Gut microbiota (GM) dysbiosis has been considered a pathogenic origin of many chronic diseases. In our previous trial, a shift in GM structure caused by a complex fiber-rich diet was associated with the health improvement of obese Prader-Willi syndrome (PWS) children. The pre- and post-intervention GMs (pre- and post-group, respectively) from one child were then transplanted into gnotobiotic mice, which resulted in significantly different physiological phenotypes, each of which was similar to the phenotype of the corresponding GM donor. This study was designed to investigate the miRNA-gene regulatory networks involved in causing these phenotypic differences. Using the post-group as a reference, we systematically identified and annotated the differentially expressed (DE) miRNAs and genes in the colon and liver of the pre-group in the second and fourth weeks after GM inoculation. Most of the significantly enriched GO terms and KEGG pathways were observed in the liver and were in the second week after GM transplantation. We screened 23 key genes along with their 73 miRNA regulators relevant to the host phenotype changes and constructed a network. The network contained 92 miRNA-gene regulation relationships, 51 of which were positive, and 41 of which were negative. Both the colon and liver had upregulated pro-inflammatory genes, and genes involved in fatty acid oxidation, lipolysis, and plasma cholesterol clearance were downregulated in only the liver. These changes were consistent with lipid and cholesterol accumulation in the host and with a high inflammation level. In addition, the colon showed an impacted glucagon-like peptide 1 (GLP-1) signaling pathway, while the liver displayed decreased insulin receptor signaling pathway activity. These molecular changes were mainly found in the second week, 2 weeks before changes in body fat occurred. This time lag indicated that GM dysbiosis might initially induce cholesterol and lipid metabolism-related miRNA and gene expression disorder and then lead to lipid accumulation and obesity development, which implicates a causative role of GM dysbiosis in obesity development rather than a result of obesity. This study provides fundamental molecular information that elucidates how dysbiotic GM increases host inflammation and disturbs host lipid and glucose metabolism.

Project description:Microbiota transplant is becoming a popular process to restore or initiate "healthy" gut microbiota and immunity. But, the potential risks of the related practices need to be carefully evaluated. This study retrospectively examined the resistomes of donated fecal microbiota for treating intestinal disorders, vaginal microbiota of pregnant women, and infant fecal microbiota from rural and urban communities, as well as the impact of transplants on the fecal resistome of human and animal recipients. Antibiotic resistance (AR) genes were found to be abundant in all donor microbiota. An overall surge of resistomes with higher prevalence and abundance of AR genes was observed in the feces of all transplanted gnotobiotic pigs as well as in the feces of infant subjects, compared to those in donor fecal and maternal vaginal microbiota. Surprisingly, transplants using rural Amish microbiota led to more instead of less AR genes in the fecal microbiota of gnotobiotic pigs than did transplants using urban microbiota. New AR gene subtypes undetected originally also appeared in gnotobiotic pigs, in Crohn's Disease (CD) patients after transplant, and in feces of infant subjects. The data illustrated the key role of the host gastrointestinal tract system in amplifying the ever-increasing AR gene pool, even without antibiotic exposure. The data further suggest that the current approaches of microbiota transplant can introduce significant health risk factor(s) to the recipients, and newborn human and animal hosts with naïve gut microbiota were especially susceptible. Given the illustrated public health risks of microbiota transplant, minimizing massive and unnecessary damages to gut microbiota by oral antibiotics and other gut impacting drugs becomes important. Since eliminating risk factors including AR bacteria and opportunistic pathogens directly from donor microbiota is still difficult to achieve, developing microbial cocktails with defined organisms and functions has further become an urgent need, should microbiota transplantation become necessary.

Dataset Information

Establishment of murine gut microbiota in gnotobiotic mice.

Publications

Establishment of murine gut microbiota in gnotobiotic mice.

Similar Datasets

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