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Inbred Mouse Populations Exhibit Intergenerational Changes in Intestinal Microbiota Composition and Function Following Introduction to a Facility.

ABSTRACT: Inbred mice are used to investigate many aspects of human physiology, including susceptibility to disease and response to therapies. Despite increasing evidence that the composition and function of the murine intestinal microbiota can substantially influence a broad range of experimental outcomes, relatively little is known about microbiome dynamics within experimental mouse populations. We investigated changes in the intestinal microbiome between C57BL/6J mice spanning six generations (assessed at generations 1, 2, 3, and 6), following their introduction to a stringently controlled facility. Fecal microbiota composition and function were assessed by 16S rRNA gene amplicon sequencing and liquid chromatography mass spectrometry, respectively. Significant divergence of the intestinal microbiota between founder and second generation mice, as well as continuing inter-generational variance, was observed. Bacterial taxa whose relative abundance changed significantly through time included Akkermansia, Turicibacter, and Bifidobacterium (p < 0.05), all of which are recognized as having the potential to substantially influence host physiology. Shifts in microbiota composition were mirrored by corresponding differences in the fecal metabolome (r = 0.57, p = 0.0001), with notable differences in levels of tryptophan pathway metabolites and amino acids, including glutamine, glutamate and aspartate. We related the magnitude of changes in the intestinal microbiota and metabolome characteristics during acclimation to those observed between populations housed in separate facilities, which differed in regards to husbandry, barrier conditions and dietary intake. The microbiome variance reported here has implications for experimental reproducibility, and as a consequence, experimental design and the interpretation of research outcomes across wide range of contexts.

SUBMITTER: Choo JM

PROVIDER: S-EPMC5387074 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Inbred Mouse Populations Exhibit Intergenerational Changes in Intestinal Microbiota Composition and Function Following Introduction to a Facility.

Choo Jocelyn M JM Trim Paul J PJ Leong Lex E X LEX Abell Guy C J GCJ Brune Carly C Jeffries Nicole N Wesselingh Steve S Dear T N TN Snel Marten F MF Rogers Geraint B GB

Frontiers in microbiology 20170411

Inbred mice are used to investigate many aspects of human physiology, including susceptibility to disease and response to therapies. Despite increasing evidence that the composition and function of the murine intestinal microbiota can substantially influence a broad range of experimental outcomes, relatively little is known about microbiome dynamics within experimental mouse populations. We investigated changes in the intestinal microbiome between C57BL/6J mice spanning six generations (assessed ...[more]

PMID: 28443082

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Project description:Sex hormone secretion difference is one of the main reasons for sexually dimorphic traits in animals, which affects the dimorphism of the intestinal microbiota; however, their interaction is still unknown. Intestinal mucosa-associated microbiota (MAM) and intestinal luminal content microbiota (LM) belong to two different habitats according to the difference in interactions between bacteria and host intestinal epithelium/nutrients. To clarify the sexually dimorphic characteristics of MAM and LM and their correlation with sex hormones, 12 specific pathogen-free (SPF) Kunming mice from the same nest were fed separately according to sex. After 8 weeks, samples from the male intestinal mucosa group (MM group), the female intestinal mucosa group (FM group), the male intestinal content group (MC group), and the female intestinal content group (FC group) were collected and then, the next-generation sequencing of 16S ribosomal ribonucleic acid (rRNA) gene was performed. Our results showed that the sexual dimorphism of MAM was more obvious than that of LM and the relative abundance of Muribaculaceae, Turicibacter, and Parasutterella was significantly higher in the FM group than in the MM group (p < 0.001, p < 0.05, p < 0.05). Next, we measured the level of serum sex hormones in mice and calculated the correlation coefficient between major bacteria and sex hormones. The results showed that the correlation between MAM and sex hormones was more prominent, and finally, three bacterial genera (Muribaculaceae, Turicibacter, and Parasutterella) were obtained, which could better represent the relationship between sexual dimorphism and sex hormones. The abundance of Parasutterella is positively and negatively correlated with estradiol and testosterone (T), respectively, which may be related to the differences in the metabolism of bile acid and glucose. A decrease in the abundance of Turicibacter is closely related to autism. Our results show that the abundance of Turicibacter is negatively and positively correlated with T and estradiol, respectively, which can provide a hint for the prevalence of male autism. In conclusion, it is proposed in our study that intestinal microbiota is probably the biological basis of physiological and pathological differences due to sex, and intestinal MAM can better represent the sexual dimorphism of mice.

Project description:BackgroundSalmonella Enteritidis (SE) is one of the major causes of human foodborne intoxication resulting from consumption of contaminated poultry products. Genetic selection of animals that are more resistant to Salmonella carriage and modulation of the gut microbiota are two promising ways to decrease individual Salmonella carriage. The aims of this study were to identify the main genetic and microbial factors that control the level of Salmonella carriage in chickens (Gallus gallus) under controlled experimental conditions. Two-hundred and forty animals from the White Leghorn inbred lines N and 61 were infected by SE at 7 days of age. After infection, animals were kept in isolators to reduce recontamination of birds by Salmonella. Caecal contents were sampled at 12 days post-infection and used for DNA extraction. Microbiota DNA was used to measure individual counts of SE by digital PCR and to determine the bacterial taxonomic composition, using a 16S rRNA gene high-throughput sequencing approach.ResultsOur results confirmed that the N line is more resistant to Salmonella carriage than the 61 line, and that intra-line variability is higher for the 61 line. Furthermore, the 16S analysis showed strong significant differences in microbiota taxonomic composition between the two lines. Among the 617 operational taxonomic units (OTU) observed, more than 390 were differentially abundant between the two lines. Furthermore, within the 61 line, we found a difference in the microbiota taxonomic composition between the high and low Salmonella carriers, with 39 differentially abundant OTU. Using metagenome functional prediction based on 16S data, several metabolic pathways that are potentially associated to microbiota taxonomic differences (e.g. short chain fatty acids pathways) were identified between high and low carriers.ConclusionsOverall, our findings demonstrate that the caecal microbiota composition differs between genetic lines of chickens. This could be one of the reasons why the investigated lines differed in Salmonella carriage levels under experimental infection conditions.

Project description:Tail-biting (TB) in pigs is a serious behavioral disorder. It is an important challenge in swine production as it impacts animal welfare and health and the economics and safety of the pork meat supply chain. To prevent TB, approaches including enrichment material and tail docking are proposed but none are optimal. Nutrition appears to be an important factor in TB behavior, perhaps by modulating the intestinal microbiota (IM). Our aim was to assess the association between TB behavior and IM in pigs through comparisons of IM in groups of biter, bitten and non-biter/non-bitten pigs. Each group composed of 12 pigs was formed at the beginning of the growing/finishing phase based on a target behavior analysis centered on TB behavior for the biter group and a score of damages caused to the tail for the bitten group. Blood and fecal samples were collected from each pig during a TB episode, at time 0, t0, and when the TB episode was considered finished, 4 weeks later, at time 1, t1. Serum cortisol level was determined by ELISA and used as an indicator of stress. The pig's fecal microbiota was analyzed from DNA extracted from freshly collected fecal matter using amplicon sequencing of the V4 hypervariable region of the 16S rRNA gene. Serum cortisol levels were significantly higher in either the biter or bitten pig groups compared to the negative control group (p = 0.02 and p = 0.01, respectively). The microbiota alpha-diversity was not significantly different between all groups, biter, bitten and negative control. Analyses of beta-diversity, however, revealed a significant difference between either the biter or the bitten group in comparison to the non-biter/non-bitten negative control group in terms of structure and composition of the microbiota. Lactobacillus were significantly more abundant in the negative control group compared to the two other groups (p = 0.001). No significant difference was revealed between the biter and bitten groups. Quantitative real-time PCR (qPCR) confirmed that lactobacilli were more abundant in the negative control group. Our study indicates that TB behavior is associated with the IM composition in pigs.

Dataset Information

Inbred Mouse Populations Exhibit Intergenerational Changes in Intestinal Microbiota Composition and Function Following Introduction to a Facility.

Publications

Inbred Mouse Populations Exhibit Intergenerational Changes in Intestinal Microbiota Composition and Function Following Introduction to a Facility.

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