Mice were injected with K/BxN serum (50 μL per mouse, i.p.; days 0 and 2) and inoculated with P. gingivalis (10⁹ CFU per mouse) or given vehicle (PBS) on days –1, 1, and 3. In addition, mice were injected i.p. on days 3 and 5 with 200 ng per mouse of RvD5_{n-3 DPA} (K/BxN + P. gingivalis + RvD5_{n-3 DPA}) or vehicle (saline plus 0.1% ethanol; K/BxN + P. gingivalis). Tissues were harvested on day 8. (A) 16S rRNA gene levels were measured by 16S qPCR in mesenteric lymph nodes (MLNs) to assess bacterial translocation across the gut barrier. Results are mean ± SEM and representative of n = 4 mice per group from 2 independent experiments; ***P ≤ 0.001 using Kruskall-Wallis test followed by Dunn’s post hoc test. (B) Representative images of 16S FISH using an Alexa Fluor 488–labeled 16S rRNA gene probe (green) to visualize bacteria and DAPI (blue) to visualize host cells in colons of arthritic vehicle-gavaged control mice and P. gingivalis–inoculated mice injected with vehicle or RvD5_{n-3 DPA}. Dotted lines outline mucus layer; arrows denote bacterial invasion into the gut epithelium (scale bars: 25 μm). Results are representative of n = 4 mice per group from 2 independent experiments. Gene expression of (C) cytokines Tgfb, Il6, Il10, and Il17a , (D) the tight junction protein Tjp1, and the antimicrobial Lyz1 was assessed in ileal mucosal tissue from arthritic mice gavaged with vehicle, inoculated with P. gingivalis, and injected i.p. with RvD5_{n-3 DPA} or controls. Results for C and D are mean ± SEM for n = 3–4 mice per group from 2 independent experiments; Kruskall-Wallis followed by Dunn’s post hoc test; *P ≤ 0.05, **P ≤ 0.01. (E) Immunofluorescence analysis of E-cadherin in small intestines from arthritic mice; scale bars: 25 μm. Results are representative of n = 4 mice per group from 2 independent experiments. (F) Ilea were harvested on day 8, and lipid mediators were identified and quantified using lipid mediator profiling in 7–8 mice per group from 2 independent experiments. (G and H) Mice were inoculated, challenged, and treated as above. (G) Clinical arthritis scores were recorded over time. Results are mean ± SEM for n = 4 mice/time point/group from 2 independent experiments; 2-way ANOVA followed by Bonferroni’s post hoc test; *P ≤ 0.05, K/BxN-injected, P. gingivalis–inoculated, vehicle-injected group (K/BxN + P. gingivalis) versus K/BxN-injected, vehicle-gavaged, vehicle-injected control group (K/BxN); ^#P ≤ 0.05, ^##P ≤ 0.01, K/BxN-injected, P. gingivalis–inoculated, RvD5_{n-3 DPA}–injected group (K/BxN + P. gingivalis + RvD5_{n-3 DPA}) versus K/BxN + P. gingivalis. (H) Swelling indices of edema formation on day 8 in paws and ankles of 8 mice per group from 2 independent experiments; *P ≤0.05 using Kruskall-Wallis followed by Dunn’s post hoc test.