益生菌對過重與肥胖者腸道健康促進與血脂調節之功效：一項隨機、雙盲與安慰劑對照之人體試食試驗

全球肥胖盛行率持續攀升，肥胖與許多高死亡率及發病率的慢性疾病有關，異常增生及肥大的脂肪細胞在代謝過程中，會使得游離脂肪酸濃度升高，導致葡萄糖使用及儲存異常，並引發脂質代謝紊亂。另外，腸道菌群的結構及功能變化調控著多種代謝反應，因此腸道菌群失衡同樣會導致代謝紊亂，與肥胖病程密切相關，然而異常的脂質代謝會生成過量的活性氧物質、氧化壓力與促發炎因子，容易誘發身體的慢性發炎反應，同時腸道的發炎作用可能會進一步導致腸道通透性增加，最終引發腸漏症。先前有研究指出，益生菌有抑制病原體、改變腸道菌群與調節宿主免疫系統之功能，也可以減少低密度脂蛋白的氧化及改善血脂。因此本研究旨在探討在過重與肥胖個體中，補充益生菌對於促進腸道健康與調節血脂的功效。本研究為一項隨機、雙盲與安慰劑對照之臨床試驗，招募50位受試者，年齡為20-65歲，身體質量指數 (body mass index, BMI) 介於25-27 kg/m2，男生體脂率 > 25%或女生體脂率 > 30%的受試者，隨機分配至益生菌組 (25人) 與安慰劑組 (25人)，持續服用4週，於每日早上空腹服用一顆安慰劑或益生菌膠囊，在試驗樣品服用前與服用4週後，進行血液常規檢查、體組成檢測、皮下脂肪厚度量測、腰圍與臀圍測量、腸道健康與排便評估問卷，以及尿液與糞便檢體之收集與分析。研究結果顯示，在服用益生菌4週後，可顯著降低受試者之體重、BMI、身體總水量、骨骼肌質量、除脂體重、體脂肪重、內臟脂肪級別、腰圍、二頭肌皮下脂肪厚度、三頭肌皮下脂肪厚度與總皮下脂肪厚度。為進一步探討益生菌對過重與肥胖者，以及不同性別受試者之影響，本研究進行獨立分層分析。分析結果顯示，在過重者與女性受試者中，在服用益生菌4週後，對體重與BMI具有更顯著之改善效果，顯示益生菌具有改善肥胖相關指標之作用。另外，有部分血脂較高的受試者 (三酸甘油酯大於100 mg/dL或總膽固醇大於200 mg/dL)，在服用益生菌4週後，可以顯著改善三酸甘油酯或總膽固醇濃度，顯示益生菌亦具有調節血脂作用。此外，腸道菌群分析結果顯示，在服用益生菌4週後，可顯著增加ACE指數 (Abundance-based coverage estimator)，也可以顯著增加Blautia的相對豐富度，而顯著減少Erysipelotrichales與Peptostreptococcaceae的相對豐富度，糞便中丁酸含量亦較服用前顯著增加，顯示出益生菌具有調節腸道菌相與促進腸道健康，且本產品之安全性指標皆無不良反應。綜上述結果得知，益生菌具有改善體重、調節血脂、調節腸道菌相與促進腸道健康等功效，因此，益生菌具有開發成調節血脂與促進腸道健康功效的膳食補充劑之潛力。

The global prevalence of obesity has been increasing, and it is highly associated with numerous chronic diseases with high mortality and morbidity. The unregulated proliferation and hypertrophy of adipocytes during the metabolism lead to elevated free fatty acid levels, causing impaired glucose utilization and storage, and inducing dyslipidemia. Additionally, alterations in the structure and function of gut microbiota regulate various metabolic mechanisms. Obesity progression is closely correlated with metabolic disorders, which are caused by gut microbiota dysbiosis. Excessive reactive oxygen species (ROS), oxidative stress, and pro-inflammatory factors were generated via abnormal lipid metabolism, which may trigger chronic inflammation. Furthermore, the gut inflammation may increase intestinal permeability, which can lead to leaky gut syndrome. Previous studies have suggested that probiotics may exert beneficial effects by inhibiting pathogens, modulating the gut microbiota, and regulating the host immune system. They may also reduce the oxidation of low-density lipoproteins and improve lipid profiles. This study aimed to investigate the effects of probiotic supplementation on promoting gut health and improving blood lipids in overweight and obese subjects. A randomized, double-blind, placebo-controlled clinical trial was conducted, recruiting 50 participants aged 20 to 65 years with a body mass index (BMI) between 25 and 27 kg/m², body fat percentage >25% in men or >30% in women. Participants were randomly assigned to the probiotic group (n = 25) or the placebo group (n = 25). They received one capsule (probiotic or placebo) every morning on an empty stomach for 4 weeks. Blood parameter analysis, anthropometric measurements, subcutaneous fat thickness measurements, waist and hip circumferences measurements, gastrointestinal health and defecation questionnaires, as well as urine and fecal sample collections were performed before and after the intervention. The results demonstrated that 4 weeks of probiotic supplementation significantly reduced body weight, BMI, total body water, skeletal muscle mass, fat-free mass, fat mass, visceral fat level, waist circumference, biceps and triceps subcutaneous fat thickness, and total subcutaneous fat thickness. To further explore the effects of probiotics on overweight and obese individuals, as well as potential differences between sexes, independent stratified analyses were conducted. The results indicated that among overweight and female subjects, probiotic supplementation for four weeks resulted in more significant improvements in body weight and BMI. These findings indicate the potential of probiotics in improving obesity-related parameters. Additionally, in a subset of participants with elevated lipid levels (triglycerides >100 mg/dL or total cholesterol >200 mg/dL), 4 weeks of probiotic intervention significantly improved triglycerides or total cholesterol levels that suggested the probiotic can reverse abnormal lipid levels. Moreover, gut microbiota analysis revealed that probiotic supplementation significantly increased the relative abundance of Blautia, while significantly decreasing Erysipelotrichales and Peptostreptococcaceae. A notable increase in the ACE diversity index and fecal butyrate contents was also observed that indicated promoted gut microbiota balance and intestinal health. Fecal lipid excretion was reduced, and no adverse effects were reported in relation to safety indicators of the product. In conclusion, the findings suggest that probiotics can effectively improve body weight, regulate blood lipids, regulate the gut microbiota, and promote intestinal health. Therefore, probiotics hold promising potential as dietary supplements for lipid regulation and gut health enhancement.