Beyond the oral niche: <i>Lacticaseibacillus paracasei</i> LPC-37 unlocks oral-gastric-intestinal crosstalk for butyric acid-dependent oral inflammation alleviation

Oral inflammatory diseases are prevalent yet poorly understood in the context of systemic microbiota interactions along the oral-gastric-intestinal axis. Current interventions primarily target direct inflammation inhibition <i>in situ</i>, leaving the cross-compartmental microbial mechanisms underlying oral inflammation underexplored. Moreover, the therapeutic potential of probiotics in modulating multi-site microbiota dynamics to alleviate oral inflammation remains limited by insufficient mechanistic insights. Using an acetic acid-induced oral inflammatory mouse model, this study systematically tracked alterations in the digestive microbiota across distinct gastrointestinal compartments during oral inflammation progression, thereby elucidating the microbiota-driven mechanisms of oral inflammation through both holistic and site-specific analyses of the digestive tract. Additionally, the potent anti-inflammatory efficacy of the commercially utilized probiotic <i>Lacticaseibacillus paracasei</i> LPC-37 was evaluated. The anti-inflammatory mechanism of LPC-37 was deciphered through microbiota structural analysis, gastrointestinal survival assessment, co-culture characterization, and short-chain fatty acid profiling. LPC-37, exhibiting robust gastrointestinal resistance, demonstrated enhanced intestinal colonization. This promoted a synergistic interaction with same-family bacteria to elevate <i>Ligilactobacillus</i> abundance, enabling antagonism against the marker microbe <i>Aerococcus</i> while upregulating <i>Clostridium saccharolyticum</i> WM1, a butyrate-producing strain. These microbial shifts drove butyrate biosynthesis, ultimately alleviating oral inflammation. The findings unravel a systemic microbiota interplay along the oral-gastric-intestinal axis and propose a novel probiotic-based strategy for anti-oral-inflammatory therapy.