Dataset Information

Temporospatial shifts within commercial laboratory mouse gut microbiota impact experimental reproducibility.

ABSTRACT: BACKGROUND:Experimental reproducibility in mouse models is impacted by both genetics and environment. The generation of reproducible data is critical for the biomedical enterprise and has become a major concern for the scientific community and funding agencies alike. Among the factors that impact reproducibility in experimental mouse models is the variable composition of the microbiota in mice supplied by different commercial vendors. Less attention has been paid to how the microbiota of mice supplied by a particular vendor might change over time. RESULTS:In the course of conducting a series of experiments in a mouse model of malaria, we observed a profound and lasting change in the severity of malaria in mice infected with Plasmodium yoelii; while for several years mice obtained from a specific production suite of a specific commercial vendor were able to clear the parasites effectively in a relatively short time, mice subsequently shipped from the same unit suffered much more severe disease. Gut microbiota analysis of frozen cecal samples identified a distinct and lasting shift in bacteria populations that coincided with the altered response of the later shipments of mice to infection with malaria parasites. Germ-free mice colonized with cecal microbiota from mice within the same production suite before and after this change followed by Plasmodium infection provided a direct demonstration that the change in gut microbiota profoundly impacted the severity of malaria. Moreover, spatial changes in gut microbiota composition were also shown to alter the acute bacterial burden following Salmonella infection, and tumor burden in a lung tumorigenesis model. CONCLUSION:These changes in gut bacteria may have impacted the experimental reproducibility of diverse research groups and highlight the need for both laboratory animal providers and researchers to collaborate in determining the methods and criteria needed to stabilize the gut microbiota of animal breeding colonies and research cohorts, and to develop a microbiota solution to increase experimental rigor and reproducibility.

SUBMITTER: Mandal RK

PROVIDER: S-EPMC7334859 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Temporospatial shifts within commercial laboratory mouse gut microbiota impact experimental reproducibility.

Mandal Rabindra K RK Denny Joshua E JE Waide Morgan L ML Li Qingsheng Q Bhutiani Neal N Anderson Charles D CD Baby Becca V BV Jala Venkatakrishna R VR Egilmez Nejat K NK Schmidt Nathan W NW

BMC biology 20200703 1

<h4>Background</h4>Experimental reproducibility in mouse models is impacted by both genetics and environment. The generation of reproducible data is critical for the biomedical enterprise and has become a major concern for the scientific community and funding agencies alike. Among the factors that impact reproducibility in experimental mouse models is the variable composition of the microbiota in mice supplied by different commercial vendors. Less attention has been paid to how the microbiota of ...[more]

PMID: 32620114

Similar Datasets

Project description:BackgroundThe changes that occur in the microbiome of aging individuals are unclear, especially in light of the imperfect correlation of frailty with age. Studies in older human subjects have reported subtle effects, but these results may be confounded by other variables that often change with age such as diet and place of residence. To test these associations in a more controlled model system, we examined the relationship between age, frailty, and the gut microbiome of female C57BL/6 J mice.ResultsThe frailty index, which is based on the evaluation of 31 clinical signs of deterioration in mice, showed a near-perfect correlation with age. We observed a statistically significant relationship between age and the taxonomic composition of the corresponding microbiome. Consistent with previous human studies, the Rikenellaceae family, which includes the Alistipes genus, was the most significantly overrepresented taxon within middle-aged and older mice. The functional profile of the mouse gut microbiome also varied with host age and frailty. Bacterial-encoded functions that were underrepresented in older mice included cobalamin (B12) and biotin (B7) biosynthesis, and bacterial SOS genes associated with DNA repair. Conversely, creatine degradation, associated with muscle wasting, was overrepresented within the gut microbiomes of the older mice, as were bacterial-encoded β-glucuronidases, which can influence drug-induced epithelial cell toxicity. Older mice also showed an overabundance of monosaccharide utilization genes relative to di-, oligo-, and polysaccharide utilization genes, which may have a substantial impact on gut homeostasis.ConclusionWe have identified taxonomic and functional patterns that correlate with age and frailty in the mouse microbiome. Differences in functions related to host nutrition and drug pharmacology vary in an age-dependent manner, suggesting that the availability and timing of essential functions may differ significantly with age and frailty. Future work with larger cohorts of mice will aim to separate the effects of age and frailty, and other factors.

Project description:Gastric cancer (GC) is one of the common malignant tumors in China, with a high morbidity and mortality. With the development and application of high-throughput sequencing technologies and metagenomics, a great quantity of studies have shown that gastrointestinal microbiota is closely related to digestive system diseases. Although some studies have reported the effect of long-term follow-up after subtotal gastrectomy on intestinal flora changes in patients with GC. However, the features of gut microbiota and their shifts in patients with GC in perioperative period remain unclear.This study was designed to characterize fecal microbiota shifts of the patients with GC before and after the radical distal gastrectomy (RDG) during their hospital staying periods. Furthermore, fecal microbiota was also compared between the GC patients and healthy individuals.Patients who were diagnosed with advanced gastric adenocarcinoma at distal stomach were enrolled in the study. The bacterial burden within fecal samples was determined using quantitative polymerase chain reaction. To analyze the diversity and composition of gut microbiota from fecal DNA of 20 GC patients and 22 healthy controls, amplicons of the 16S rRNA gene from all subjects were pyrosequenced. To study gut microbiota shifts, the fecal microbiota from 6 GC patients before and after RDG was detected and subsequently analyzed. Short-chain fatty acids were also detected by chromatography spectrometer in these 6 GC patients.RDG had a moderate effect on bacterial richness and evenness, but had pronounced effects on the composition of postoperative gut microbiota compared with preoperative group. The relative abundances of genera Akkermansia, Esherichia/Shigella, Lactobacillus, and Dialister were significant changed in perioperative period. Remarkably, higher abundances of Escherichia/Shigella, Veillonella, and Clostridium XVIII and lower abundances of Bacteroides were observed in gut microbiota of overall GC patients compared to healthy controls.This study is the first study to characterize the altered gut microbiota within fecal samples from GC patients during perioperative period, and provide a new insights on such microbial perturbations as a potential effector of perioperative period phenotype. Further research must validate these discoveries and may evaluate targeted microbiota shifts to improve outcomes in GC patients.

Project description:BackgroundMicrobiota development is a critical aspect of turkey poult maturation, and the succession of microbes in the turkey gut has been shown to correlate with poult performance. The purpose of this study was to determine the fate of the microbiota in turkey poults after movement of birds first raised in an isolated hatch brood system into a more traditional commercial brood facility with pre-existing birds. Turkey poults were first divided into groups raised in conventional brood pens from day-of-hatch and those raised in an experimental hatch brood system. After 11 days of growth, hatch brood birds were moved into pens within the conventional brood barn and monitored for an additional 18 days. Sampling of both hatch brood and conventional pen birds was performed at multiple timepoints throughout the study, and cecal content was used to analyze the bacterial microbiota using 16S rRNA gene amplicon sequencing.ResultsAlpha diversity tended to be higher in samples from conventional pen birds compared to those from hatch brood birds prior to the day 11 move, but the difference between systems was not observed post-move. Using beta diversity metrics, bacterial community succession appeared delayed in the hatch brood system birds pre-move, but post-move community composition quickly converged with that of the conventional pen birds. This was validated through assessment of significantly different genera between hatch brood system and conventional pen birds, where numbers of significantly different taxa quickly decreased following the move. Some key taxa previously associated with poult performance were delayed in their appearance and relative abundance in hatch brood birds.ConclusionsOverall, this study demonstrates that the use of isolated hatch brood systems has an impact on the poult gut microbiota, but its impact is resolved quickly once the birds are introduced into a conventional brood environment. Therefore, the benefits of pathogen reduction with hatch brood systems may outweigh negative microbiota impacts due to isolation.

Dataset Information

Temporospatial shifts within commercial laboratory mouse gut microbiota impact experimental reproducibility.

Publications

Temporospatial shifts within commercial laboratory mouse gut microbiota impact experimental reproducibility.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets