AUTHOR=Huang Lan , Ge Song , Yang Kun , Duan Lian , Gao Li , Li Yu Zhen , Yi Yu Shi 

TITLE=Effects of oral gavage with periodontal pathogens and plaque biofilm on gut microbiota ecology and intestinal tissue architecture in mice: a mechanistic study

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=Volume 15 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2025.1589055

DOI=10.3389/fcimb.2025.1589055

ISSN=2235-2988

ABSTRACT=ObjectiveThis study aimed to establish an in vitro model simulating periodontal biofilm architecture with three representative periodontal pathogens and evaluate its systemic impact through oral gavage administration in C57BL/6 mice. The findings provide mechanistic insights into the oral-gut axis dysbiosis, elucidating potential pathways linking periodontal inflammation to gastrointestinal pathophysiology.MethodsFifty 7-week-old male C57BL/6 mice were randomized into five groups(n=10/group): control (H), F. nucleatum (F), P.gingivalis (P), S.sanguinis (S) and biofilm (BF, F.n + P.g + S.s) groups. Mice were gavaged twice weekly for 6 weeks with 1×109 CFU (F, P, BF groups) and 1×108 CFU (S group) of bacterial suspensions or PBS (H group). Post-intervention, fecal and colon tissues were collected for 16S rRNA sequencing, H&E staining, immunohistochemistry (Occludin expression), and qRT-PCR analysis of inflammatory markers(IL18, TNF-α, IL-1β, B220, F4/80, NOS2, ARG1).ResultsA stable in vitro three-species biofilm model was successfully established to mimic the ecology of periodontal plaque. Gavage with F.n, P.g or the biofilm consortium (BF group) induced intestinal barrier disruption and elevated pro-inflammatory cytokines levels. PCR indicated a significant increase in the expression of IL-1β, TNF-α, B220, F4/80, and NOS2 in the P group (P < 0.001), while Arg-1 expression exhibited a significant decrease (P < 0.01). In the BF group, only TNF-α expression demonstrated a significant increase (P < 0.01). The expression of occludin is significantly reduced in the F/P/BF group, with the most pronounced decrease observed in the P group (P < 0.01). Gut microbiota alterations occurred in all groups. At the phylum level, the Firmicutes/Bacteroidetes (F/B) ratio increased in all three groups (F/P/BF group). Proteobacteria abundance rose substantially in the P group, while Desulfovibrio increased and Verrucomicrobia decreased in the F/P/BF and F/S groups, respectively. Genus-level analysis showed reduced Muribaculaceae in the F/P/BF group, alongside elevated pro-inflammatory bacteria (e.g., Enterococcus, Acinetobacter) and diminished beneficial bacteria (e.g., Bifidobacterium, Parabacteroides).ConclusionThese findings demonstrate that periodontal pathogens induce gut barrier compromise through microbiome-driven immunomodulation, with P. gingivalis exhibiting predominant pro-inflammatory effects.