Oral bacteria colonize and compete with gut microbiota in gnotobiotic mice

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.

Carrageenan oligosaccharides and associated carrageenan-degrading bacteria induce intestinal inflammation in germ-free mice

Carrageenans(CGNs)are widely used in foods and pharmaceuticals although their safety remains controversial.To investigate the effects of CGNs and CGN-degrading bacteria in the human colon,we screened for CGN degradation by human fecal microbiota,and for inflammatory response to CGNs and/or CGN-degrading bacteria in germ free mice.Thin-layer chromatography indicated that high molecular weight(MW)CGNs(!100 kDa)remained undegraded in the presence of human fecal microbiota,whereas low MW CGNs,i.e.,k-carrageenan oligosaccharides(KCO,~4.5 kDa)were degraded when exposed to seven of eight human fecal samples,although sulfate groups were not removed during degradation.Bacteroides xylanisolvens and Escherichia coli isolates from fecal samples apparently degraded KCO synergistically,with B.xylanisolvens serving as the primary degrader.Combined treatment of KCO with KCO-degrading bacteria led to greater pro-inflammatory effects in the colon and rectum of germ-free mice than either KCO or bacteria alone.Similarly,p-p38-,CD3-,and CD79a-positive immune cells were more abundant in combined treatment group mice than in either single treatment group.Our study shows that KCO-degrading bacteria and the low MW products of KCO can promote proinflammatory effects in mice,and represent two key markers for evaluating CGN safety in foods or medicines.