Pagnini Cristiano, Di Paolo Maria Carla, Urgesi Riccardo, Pallotta Lorella, Fanello Gianfranco, Graziani Maria Giovanna, Delle Fave Gianfranco
Department of Gastroenterology and Digestive Endoscopy, S. Giovanni Addolorata Hospital, Via dell'Amba Aradam 9, 00184 Rome, Italy.
Department of Gastroenterology, "Sapienza" University of Rome, 00185 Rome, Italy.
Microorganisms. 2023 May 24;11(6):1381. doi: 10.3390/microorganisms11061381.
Probiotics are microorganisms that confer benefits to the host, and, for this reason, they have been proposed in several pathologic states. Specifically, probiotic bacteria have been investigated as a therapeutic option in ulcerative colitis (UC) patients, but clinical results are dishomogeneous. In particular, many probiotic species with different therapeutic schemes have been proposed, but no study has investigated probiotics in monotherapy in adequate trials for the induction of remission. GG (LGG) is the more intensively studied probiotic and it has ideal characteristics for utilization in UC patients. The aim of the present study is to investigate the clinical efficacy and safety of LGG administration in an open trial, delivered in monotherapy at two different doses, in UC patients with mild-moderate disease. The UC patients with mild-moderate disease activity (Partial Mayo score ≥ 2) despite treatment with oral mesalamine were included. The patients stopped oral mesalamine and were followed up for one month, then were randomized to receive LGG supplement at dose of 1.2 or 2.4 × 10 CFU/day for one month. At the end of the study, the clinical activity was evaluated and compared to that at the study entrance (efficacy). Adverse events were recorded (safety). The primary end-point was clinical improvement (reduction in the Partial Mayo score) and no serious adverse events, while the secondary end-points were the evaluation of different efficacies and safeties between the two doses of LGG. The patients with disease flares dropped out of the study and went back to standard therapy. The efficacy data were analyzed in an intention-to-treat (ITT) and per-protocol (PP) analysis. Out of the 76 patients included in the study, 75 started the probiotic therapy ( = 38 and 37 per group). In the ITT analysis, 32/76 (42%) responded to treatment, 21/76 (28%) remained stable, and 23/76 (30%) had a worsening of their clinical condition; 55 (72%) completed the treatment and were analyzed in a PP analysis: 32/55 (58%) had a clinical response, 21 (38%) remained stable, and 2 (4%) had a light worsening of their clinical condition ( < 0.0001). Overall, 37% of the patients had a disease remission. No severe adverse event was recorded, and only one patient stopped therapy due to obstinate constipation. No difference in the clinical efficacy and safety has been recorded between groups treated with different doses of LGG. The present prospective clinical trial demonstrates, for the first time, that LGG in monotherapy is safe and effective for the induction of remission in UC patients with mild-moderate disease activity (ClinicalTrials.gov identifier: NCT04102852).
益生菌是对宿主有益的微生物，因此，它们已被应用于多种病理状态。具体而言，益生菌已被作为溃疡性结肠炎（UC）患者的一种治疗选择进行研究，但临床结果并不一致。特别是，已经提出了许多具有不同治疗方案的益生菌种类，但尚无研究在足够的诱导缓解试验中对单一疗法中的益生菌进行研究。鼠李糖乳杆菌GG（LGG）是研究最深入的益生菌，它具有在UC患者中使用的理想特性。本研究的目的是在一项开放试验中，以两种不同剂量的单一疗法，研究LGG给药对轻度至中度疾病的UC患者的临床疗效和安全性。纳入尽管接受口服美沙拉嗪治疗但疾病活动仍为轻度至中度（部分梅奥评分≥2）的UC患者。患者停用口服美沙拉嗪并随访1个月，然后随机接受剂量为1.2或2.4×10CFU/天的LGG补充剂治疗1个月。在研究结束时，评估临床活动并与研究开始时的情况进行比较（疗效）。记录不良事件（安全性）。主要终点是临床改善（部分梅奥评分降低）且无严重不良事件，次要终点是评估两种剂量LGG之间不同的疗效和安全性。疾病发作的患者退出研究并恢复标准治疗。疗效数据采用意向性分析（ITT）和符合方案分析（PP）进行分析。在纳入研究的76例患者中，75例开始了益生菌治疗（每组38例和37例）。在ITT分析中，32/76（42%）对治疗有反应，21/76（28%）病情稳定，23/76（30%）临床状况恶化；55例（72%）完成治疗并进行PP分析：32/55（58%）有临床反应，21例（38%）病情稳定，2例（4%）临床状况轻度恶化（P<0.0001）。总体而言，37%的患者病情缓解。未记录到严重不良事件，只有1例患者因顽固性便秘停止治疗。不同剂量LGG治疗组之间在临床疗效和安全性方面未记录到差异。本前瞻性临床试验首次证明，单一疗法中的LGG对轻度至中度疾病活动的UC患者诱导缓解是安全有效的（ClinicalTrials.gov标识符：NCT04102852）。
