Abstract

The oral microbiota is associated with oral diseases and digestive systemic diseases. Nevertheless, the causal relationship between them has not been completely elucidated, and colonisation of the gut by oral bacteria is not clear due to the limitations of existing research models. The aim of this study was to develop a human oral microbiota-associated (HOMA) mouse model and to investigate the ecological invasion into the gut. By transplanting human saliva into germ-free (GF) mice, a HOMA mouse model was first constructed. 16S rRNA gene sequencing was used to reveal the biogeography of oral bacteria along the cephalocaudal axis of the digestive tract. In the HOMA mice, 84.78% of the detected genus-level taxa were specific to the donor. Principal component analysis (PCA) revealed that the donor oral microbiota clustered with those of the HOMA mice and were distinct from those of specific pathogen-free (SPF) mice. In HOMA mice, OTU counts decreased from the stomach and small intestine to the distal gut. The distal gut was dominated by Streptococcus, Veillonella, Haemophilus, Fusobacterium, Trichococcus and Actinomyces. HOMA mice and human microbiota-associated (HMA) mice along with the GF mice were then cohoused. Microbial communities of cohoused mice clustered together and were significantly separated from those of HOMA mice and HMA mice. The Source Tracker analysis and network analysis revealed more significant ecological invasion from oral bacteria in the small intestines, compared to the distal gut, of cohoused mice. In conclusion, a HOMA mouse model was successfully established. By overcoming the physical and microbial barrier, oral bacteria colonised the gut and profiled the gut microbiota, especially in the small intestine.

Highlights

  • Clinical trials have indicated that the oral microbiota is associated with dental caries and periodontitis,[1,2,3,4] both of which give rise to an extensive loss of natural teeth in older people and are identified as public health problems worldwide.[5]

  • We studied the competition of oral microbiota with the native gut microbiota in various regions of the gut and identified key bacteria during the ecological invasion, by cohousing human oral microbiota-associated (HOMA) mice, human microbiota-associated (HMA) mice and GF mice (Fig. 1)

  • The oral microbiota of the HOMA mouse model The surveys of oral samples revealed the engraftment of the human oral microbiota: all bacterial phyla, classes, orders, 27 of 28 bacterial families, and 84.78% (39 of 46) of genus-level taxa were detected among the recipient mice

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Summary

Introduction

Clinical trials have indicated that the oral microbiota is associated with dental caries and periodontitis,[1,2,3,4] both of which give rise to an extensive loss of natural teeth in older people and are identified as public health problems worldwide.[5]. Regardless, a prospective cohort clinical study[9] found that shifts in the microbiota preceded the manifestation of clinical symptoms of ECC. Most of the other studies were cross-sectional and could barely address whether the oral microbiota was the cause or effect in the development of oral diseases. In-vitro models have limitations due to the abundant uncultivated phylotypes in the mouth.[10] Animal models would have been considered a good choice to study the oral microbiota; the oral microbiota of mice, the most common experiment animal model, differs from that of humans

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