Amuc_1100

Alterations in the intestinal microbiota contribute to the pathogenesis of various cardiovascular disorders, but how they affect the development of Kawasaki disease (KD) an acute pediatric vasculitis, remains unclear.

We used the Lactobacillus casei cell wall extract (LCWE) murine model of KD vasculitis to assess the contribution of the intestinal microbiota to the development of vascular inflammation. We evaluated the severity of vasculitis in microbiota-depleted mice. 16S rRNA gene sequencing was used to characterize the fecal microbiome composition of LCWE-injected mice. Some groups of mice were orally treated with selected live or pasteurized bacteria, short-chain fatty acids, or Amuc_1100, the Toll-like receptor 2 signaling outer membrane protein from Akkermansia muciniphila , and their impact on vasculitis development was assessed.

We report that depleting the gut microbiota reduces the development of cardiovascular inflammation in a murine model mimicking KD vasculitis. The development of cardiovascular lesions was associated with alterations in the intestinal microbiota composition and, notably, a decreased abundance of Akkermansia muciniphila and Faecalibacterium prausnitzii . Oral supplementation with either of these live or pasteurized individual bacteria or with short-chain fatty acids produced by them attenuated cardiovascular inflammation, as reflected by decreased local immune cell infiltrations. Treatment with Amuc_1100 also reduced the severity of vascular inflammation.

This study reveals an underappreciated gut microbiota-cardiovascular inflammation axis in KD vasculitis pathogenesis and identifies specific intestinal commensals that regulate vasculitis in mice by producing metabolites or via extracellular proteins capable of enhancing and supporting gut barrier function.

Lung adenocarcinoma (LUAD) stands out as a prevalent malignant tumor necessitating innovative strategies to enhance therapeutic outcomes. Akkermansia muciniphila (AKK) has emerged as intricately linked to tumor immunotherapy, yet its impact on natural killer (NK) cells, which play a crucial role in immunotherapy, remains unclear. This study aims to investigate the effects of AKK outer membrane proteins on NK cells in LUAD and elucidate potential associated molecular mechanisms. 16S rRNA sequencing was employed to analyze bacterial genera and their abundance in fecal samples from LUAD patients. Co-culturing of NK-92 cells with LUAD cells, with or without treatment of AKK outer membrane protein Amuc_1100, was conducted to investigate the mechanisms of AKK on LUAD. Additionally, a xenograft mouse model was established to validate the effects of AKK in an in vivo setting. The experimental findings indicated that LUAD patients with elevated AKK levels in their fecal samples demonstrated increased NK cell infiltration and reduced TGF-β levels. Treatment with Amuc_1100 elevated TNF-α and IL-15 cytokine levels, decreased TGF-β levels and proteins associated with TGF-β pathway, enhanced NK cell cytotoxicity, upregulated perforin and granzyme B expression, induced apoptosis and cell cycle arrest, thereby inhibiting cancer cell proliferation. Amuc_1100 also impeded tumor growth in vivo. In summary, these results suggest that AKK activates NK cells to target tumor cells by suppressing the TGF-β signaling pathway in LUAD cells, underscoring the potential of Akk as an effective immunotherapeutic agent in LUAD NK cell-directed therapies.