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Establishment and Stability of the Murine Oral Microbiome.

ABSTRACT: Commensal microbiomes exert critical functions at barrier sites. In particular, establishment of the commensal microbiome after birth dictates immune functionality and tissue homeostasis at mucosal surfaces. To investigate the establishment and stability of the oral mucosal microbiome in mice, we evaluated oral microbiome communities shortly after birth, through adulthood, and up to 1 y of life in a controlled manner, using sequential oral samples from the same mice over time. We further evaluated transmissibility of oral microbiomes from parents and during cohousing experiments and evaluated susceptibility to oral inflammatory disease in mice harboring distinct microbiomes. Our work reveals basic principles in the establishment and stability of a health-associated oral microbiome after birth and provides insights that may be important for host-microbiome experimentation in animal models.

SUBMITTER: Abusleme L

PROVIDER: S-EPMC7243417 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Abstract Early life exposures to antibiotics negatively impact respiratory health and are associated with an increased risk of childhood asthma. It is explained that the lung is inclined to develop chronic inflammatory phenotypes due to early antibiotic alteration in the gut microbiome. We investigated whether a gut‐targeted antibiotic has an impact on the lung microbiome and on pulmonary immunity. Fourteen‐day old C57BL/6 mice were administered with vancomycin via oral gavage for 3 days (1 time/day). Control groups were treated with clarithromycin and phosphate‐buffered saline (PBS), respectively. Five days after treatment, the cecum and lung microbiome, and pulmonary immune response were analyzed. Vancomycin treatment decreased the relative abundance of the genera Clostridium XIVa and Alistipes and the family Lachnospiraceae in the cecum. Furthermore, the relative abundance of the family Parabacteroidetes and the genus Lactobacillus were increased, whereas the abundance of the phylum Firmicutes was decreased. In the lung, vancomycin treatment reduced bacteria belonging to Clostridium XIVa and the family Lachnospiraceae as compared to those in the clarithromycin treated group. Lung cells from the vancomycin‐treated mice released higher levels of interleukin (IL)‐4 and IL‐13 compared to those from the PBS group, and increased levels of IL‐6, IFN‐γ, and TNFα compared to lung cells from the clarithromycin and PBS treated mice. Our pilot study suggests that alteration in the gut microbiome could affect bacterial composition and immunity of the lung hence proposes a gut–lung microbiome axis in early life. Early life exposures to antibiotics negatively impact respiratory health and are associated with an increased risk of childhood asthma. We investigated whether a gut‐targeted antibiotic has an impact on the lung microbiome and on pulmonary immunity. Our pilot study suggests that alteration in the gut microbiome could affect bacterial composition and immunity of the lung hence proposing a gut–lung microbiome axis in early life.

Project description:Significant evidence supports a relationship between the gut microbiome, inflammation, host response, and health, including the finding that a number of disorders are associated with disruption of the microbiome. In these disorders, a number of dietary interventions (including prebiotics, live probiotics, or heat-killed microbes) have been proposed to be curative or preventative agents. The use of heat-killed microbes has a number of benefits over living organisms, including reduced infection risk in vulnerable individuals, extended shelf life and the potential for use in combination with antimicrobial agents. We previously reported that murine chow supplemented with 5% ADR-159, a heat-treated fermentate generated by two Lactobacillus strains, altered both behavior and the microbiome of male mice. Now we show that ADR-159 fed female mice also display a similar microbiome shift as determined by 16S rDNA analysis. In particular, we observed a reduction of levels of Turicibacter and Clostridium sensu stricto. These subtle changes in the bacterial component of the microbiome were mirrored by changes in the virome. Extended consumption of the ADR-159 diet had no negative effect on general health and lipocalin 2 levels (LCN2; a proxy for inflammation), but we observed increased IL-17f and decreased IL-12α expression in the colon and decreased short chain fatty acid levels in the ADR-159 fed animals. Four weeks into the diet, half of the animals were dosed with Citrobacter to determine the effect of ADR-159 on infection and on pathogen induced colitis. Overall, our results suggest that while the ADR-159 diet does not prevent Citrobacter infection, it had an effect on Citrobacter-induced inflammation. In contrast to animals fed standard chow, ADR-159 fed animals did not show a reduction of small intestine length and increase of colon crypt depth, which occurred in control mice. These microbiological, histological, and immunological results provide evidence to support the impact of heat-treated microorganisms and their metabolites on the murine microbiome and health.

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Establishment and Stability of the Murine Oral Microbiome.

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