Abstract

Teichoic acid (TA) derived from different Gram-positive bacteria exhibit distinct effects on host inflammatory responses. In this study, we investigated the inflammation modulation of TAs from Lactiplantibacillus plantarum ( L. plantarum ) AR113 by AR113 key TA-synthesizing gene knockout strains. Our findings show that the presence of TAs attenuated the anti-inflammatory activity of AR113 by diminished pro-inflammatory signaling pathway triggered by TLR2 (MyD88/MAPK axis) in macrophages. And ultimately manifested in vitro with AR113Δ ltas stimulated cells to produce nitric oxide (NO) at 15.8% lower, AR113Δ dlt at 48.5% lower, and AR113ΔtagO at 51.2% lower levels compared to AR113 ( p < 0.05). In addition, whether in vitro or in vivo , AR113Δ tagO effectively could reduce pro-inflammatory cytokine production, while AR113Δ ltas and AR113Δ dlt could promoted the production of anti-inflammatory cytokine than AR113. Notably, D-Ala branch chain appears to be a key factor in the inflammatory response to TAs produced by AR113, since only the cytotoxic effect of AR113Δ dlt on macrophages was significantly reduced compare to AR113 ( p < 0.01); and that AR113Δ dlt demonstrated the most effective relief of colitis symptoms, reducing the disease activity index (DAI) better than the AR113 intervention group (4.45±1.73 vs 5.30±1.85). However, further studies on the intestinal barrier in mice shown that TAs produced by AR113 had no significant effect on barrier-related genes, indicates that the TAs does not cause damage to the intestinal barrier of mice, they primarily target immune responses. Overall, this study identifies potential targets for enhancing the anti-inflammatory properties of probiotics.