과민성 장증후군에서 복합 생균제의 효과와 장내 세균총의 변화

Abstract

서론: 최근 과민성 장증후군 치료에 생균제가 많이 사용되고 있다. 본 연구는 과민성 장증후군에서 여러 종류의 균이 포함된 복합 생균제 제재의 치료 효과 및 생균제 제재 투여에 의한 장내 세균총 변화와 증상 호전과의 연관성에 대해 알아보고자 하였다. 방법: ROME III 진단기준에 부합하는 49명의 과민성 장증후군 환자를 대상으로 이중 맹검 무작위 위약-대조군 임상연구를 시행하였다. 연구 대상자는 무작위 배정으로 4주 동안 복합 생균제 제재(락크린 골드 S: Bifidobacterium longum, Bifidobacterium bifidum, Bifidobacterium lactis, Lactobacillus acidophilus, Lactobacillus rhamnosus, Streptococcus thermophilus) 또는 위약을 복용하였다. 1차 유효성 평가변수로 4주 치료 후 과민성 장증후군 증상의 전반적인 호전 여부를 알아보았다. 2차 유효성 평가변수로 4주 치료 후 복통, 복부 불편감, 복부 팽만감, 대변 횟수, 대변 성상의 호전 정도, 그리고 장내 세균총 변화와 증상 호전과의 연관성을 알아보았다. 대변 세균총은 34명에서(생균제 군: 17명, 위약 군: 17명) 검사하였고 실시간 유전자증폭 정량분석을 이용하였다. 결과: 총 49명의 환자(생균제 군: 25명, 위약 군: 24명)에서 Intention-to-treat 분석을 시행하였다. 4주 후 과민성 장증후군 증상의 전반적인 호전은 생균제 군에서 위약 군보다 통계학적으로 유의하게 높았다: 68%(17/25) vs. 37.5% (9/24) (p < 0.05). 2차 유효성 평가변수인 복통, 복부 불편감, 복부 팽만감도 생균제 군에서 위약 군보다 유의한 호전을 보였다. 대변 세균총 분석 결과 생균제 군에서는 B. lactis, L. rhamnosus, S. thermophilus가 통계학적으로 유의하게 증가한 반면 위약 군에서는 B. lactis만 통계학적으로 유의한 증가를 보였다. B. lactis가 증가한 군에서 그렇지 않은 군에 비해 복통의 의미있는 호전을 보였다(p < 0.05). 결론: 복합 생균제 제재는 과민성 장증후군 증상을 통계학적으로 유의하게 개선시켰다. 복합 생균제 투여 후 대변 세균총의 변화를 보였으며 대변 세균총 변화와 과민성 장증후군의 증상 개선은 연관성을 보였다.|Background: Probiotics are commonly prescribed for treating the patients with irritable bowel syndrome (IBS) because recent studies showed that intestinal microbiota was altered in IBS patients. We investigated the efficacy of multi-species probiotics on IBS symptoms and the relationship between the alterations of gut microbiota and symptomatic improvement of IBS symptoms after probiotics supplement. Methods: This randomized, double-blinded, and placebo-controlled trial was performed in 49 IBS patients diagnosed according to the Rome III criteria. Subjects were randomized to receive multi-species probiotics (mixture of Bifidobacterium longum, Bifidobacterium bifidum, Bifidobacterium lactis, Lactobacillus acidophilus, Lactobacillus rhamnosus, and Streptococcus thermophilus – twice a day) or placebo for 4 weeks. Primary efficacy endpoint was the proportion of participants who had a global relief of IBS symptoms at week 4. Secondary endpoints were the intensity of abdominal pain/discomfort, bloating, stool frequency/consistency, the alterations of fecal microflora during 4 weeks, and the relationship between the alterations of gut microbiota and the improvement of IBS symptoms. Fecal microflora was analyzed in 34 patients (probiotics: 17, placebo: 17) by quantitative real-time PCR assays. Results: A total of 49 patients (probiotics: 25, placebo: 24) were analyzed by the intention-to-treat approach. The proportion of patients who had received global relief of IBS symptoms at week 4 was significantly higher in probiotics group than placebo group: 68.0% (17/25) vs. 37.5% (9/24) (p < 0.05). The secondary endpoints such as improvement of abdominal pain/discomfort and bloating were achieved in probiotics group rather than placebo group. In fecal analysis, B. lactis, L. rhamnosus, and S. thermophilus were significantly increased in the probiotics group after 4 weeks while B. lactis was increased in placebo group. Abdominal pain was significantly improved in the group showing the increase of B. lactis counts (p < 0.05). Conclusions: Multi-species probiotics are efficacious in IBS patients and the alterations of intestinal microbiota are associated with the symptomatic improvement.; Background: Probiotics are commonly prescribed for treating the patients with irritable bowel syndrome (IBS) because recent studies showed that intestinal microbiota was altered in IBS patients. We investigated the efficacy of multi-species probiotics on IBS symptoms and the relationship between the alterations of gut microbiota and symptomatic improvement of IBS symptoms after probiotics supplement. Methods: This randomized, double-blinded, and placebo-controlled trial was performed in 49 IBS patients diagnosed according to the Rome III criteria. Subjects were randomized to receive multi-species probiotics (mixture of Bifidobacterium longum, Bifidobacterium bifidum, Bifidobacterium lactis, Lactobacillus acidophilus, Lactobacillus rhamnosus, and Streptococcus thermophilus – twice a day) or placebo for 4 weeks. Primary efficacy endpoint was the proportion of participants who had a global relief of IBS symptoms at week 4. Secondary endpoints were the intensity of abdominal pain/discomfort, bloating, stool frequency/consistency, the alterations of fecal microflora during 4 weeks, and the relationship between the alterations of gut microbiota and the improvement of IBS symptoms. Fecal microflora was analyzed in 34 patients (probiotics: 17, placebo: 17) by quantitative real-time PCR assays. Results: A total of 49 patients (probiotics: 25, placebo: 24) were analyzed by the intention-to-treat approach. The proportion of patients who had received global relief of IBS symptoms at week 4 was significantly higher in probiotics group than placebo group: 68.0% (17/25) vs. 37.5% (9/24) (p < 0.05). The secondary endpoints such as improvement of abdominal pain/discomfort and bloating were achieved in probiotics group rather than placebo group. In fecal analysis, B. lactis, L. rhamnosus, and S. thermophilus were significantly increased in the probiotics group after 4 weeks while B. lactis was increased in placebo group. Abdominal pain was significantly improved in the group showing the increase of B. lactis counts (p < 0.05). Conclusions: Multi-species probiotics are efficacious in IBS patients and the alterations of intestinal microbiota are associated with the symptomatic improvement.