Efficacy of ETB-F01, Heat-Killed Akkermansia muciniphila Strain EB-AMDK19, in Patients with Respiratory Symptoms: A Multicenter Clinical Trial

Respiratory symptoms are prevalent in the general population, and they are associated with a decline in lung function and increased mortality. The gut-lung connection suggests intestinal dysbiosis may impact lung diseases, with <i>Akkermansia muciniphila</i> showing promise in regulating extraintestinal diseases. However, its application in patients with respiratory symptoms lacks clinical trial evidence. In this randomized, double-blind trial, ETB-F01, containing heat-killed <i>A. muciniphila</i> strain EB-AMDK19, was compared with a placebo in patients experiencing respiratory symptoms for 4 to 12 weeks. The primary outcome was improvement in Breathlessness, Cough, and Sputum Scale (BCSS) score over 12 weeks. Secondary outcomes included lung function, fractional exhaled nitric oxide (FeNO), modified Medical Research Council (mMRC) dyspnea scale, St. George's Respiratory Questionnaire (SGRQ), and Visual Analog Scale (VAS) score. The primary analysis was performed in the per-protocol set, with a sensitivity analysis in the full analysis set. In the per-protocol population, 68 participants were randomly assigned to the ETB-F01 group and 65 to the placebo group. ETB-F01 had a superior efficacy over placebo in improving BCSS total scores (between-group difference = -0.8 (95% confidence interval, -1.4--0.3), <i>p</i>-value = 0.004). Specifically, there was a significant reduction in BCSS breathlessness and cough domain scores with ETB-F01. While trends toward improvement in lung function were noted, statistical significance was not achieved. No significant differences were observed in FeNO and other symptom scores (mMRC, SGRQ, and VAS). In safety profile, ETB-F01 did not cause any serious adverse events. These results suggest that ETB-F01 is safe and effective for alleviating respiratory symptoms.