Department of Kinesiology and Physical Education, University of Lethbridge, 4401 University Drive, Lethbridge, AB, T1K 3M4, Canada.
Faculty of Kinesiology, University of Calgary, 2500 University Drive NW, Calgary, AB, T2N 1N4, Canada.
Eur J Nutr. 2019 Jun;58(4):1735-1745. doi: 10.1007/s00394-018-1721-2. Epub 2018 May 19.
In obesity and diabetes the liver is highly susceptible to abnormal uptake and storage of fat. In certain individuals hepatic steatosis predisposes to the development of non-alcoholic steatohepatitis (NASH), a disease marked by hepatic inflammation and fibrosis. Although the precise pathophysiology of NASH is unknown, it is believed that the gut microbiota-liver axis influences the development of this disease. With few treatment strategies available for NASH, exploration of gut microbiota-targeted interventions is warranted. We investigated the therapeutic potential of a prebiotic supplement to improve histological parameters of NASH.
In a placebo-controlled, randomized pilot trial, 14 individuals with liver-biopsy-confirmed NASH [non-alcoholic fatty liver activity score (NAS) ≥ 5] were randomized to receive oligofructose (8 g/day for 12 weeks followed by 16 g/day for 24 weeks) or isocaloric placebo for 9 months. The primary outcome measure was the change in liver biopsy NAS score and the secondary outcomes included changes in body weight, body composition, glucose tolerance, inflammatory markers, and gut microbiota.
Independent of weight loss, oligofructose improved liver steatosis relative to placebo and improved overall NAS score (P = 0.016). Bifidobacterium was enhanced by oligofructose, whereas bacteria within Clostridium cluster XI and I were reduced with oligofructose (P < 0.05). There were no adverse side effects that deterred individuals from consuming oligofructose for treatment of this disease.
Independent of other lifestyle changes, prebiotic supplementation reduced histologically-confirmed steatosis in patients with NASH. Larger follow-up studies are warranted.
This trial was registered at Clinicaltrials.com as NCT03184376.
在肥胖和糖尿病患者中，肝脏极易异常摄取和储存脂肪。在某些个体中，肝脂肪变性会导致非酒精性脂肪性肝炎（NASH）的发生，这是一种以肝炎症和纤维化为特征的疾病。尽管 NASH 的确切病理生理学机制尚不清楚，但人们认为肠道微生物群-肝脏轴会影响这种疾病的发展。由于目前针对 NASH 的治疗策略有限，因此有必要探索针对肠道微生物群的干预措施。我们研究了一种益生元补充剂改善 NASH 组织学参数的治疗潜力。
在一项安慰剂对照、随机临床试验中，14 名经肝活检证实患有 NASH 的患者（非酒精性脂肪肝活动评分 [NAS] ≥ 5）被随机分为接受低聚果糖（8g/天，持续 12 周，然后 16g/天，持续 24 周）或等热量安慰剂治疗 9 个月。主要终点是肝活检 NAS 评分的变化，次要终点包括体重、身体成分、葡萄糖耐量、炎症标志物和肠道微生物群的变化。
独立于体重减轻，低聚果糖改善了肝脏脂肪变性，相对于安慰剂改善了总体 NAS 评分（P=0.016）。双歧杆菌因低聚果糖而增加，而梭菌簇 XI 和 I 内的细菌则因低聚果糖而减少（P<0.05）。低聚果糖没有不良的副作用，不会阻止个体用它来治疗这种疾病。
在不进行其他生活方式改变的情况下，益生元补充剂可减少 NASH 患者经组织学证实的脂肪变性。需要更大规模的随访研究。
这项试验在 Clinicaltrials.com 上注册为 NCT03184376。
