Pathogen Molecular Genetics Section, Laboratory of Bacteriology, National Institute of Allergy and Infectious Diseases, US National Institutes of Health, Bethesda, MD, USA.
Faculty of Veterinary Science, Rajamangala University of Technology Srivijaya, Nakhon Si Thammarat, Thailand.
Lancet Microbe. 2023 Feb;4(2):e75-e83. doi: 10.1016/S2666-5247(22)00322-6. Epub 2023 Jan 13.
Decolonisation is considered a valuable means to reduce Staphylococcus aureus infection rates. However, previous topical strategies targeting the nose or skin had little success, and oral antibiotic-based decolonisation is ill advised because of eradication of the microbiota and development of antibiotic resistance. We previously showed that the probiotic Bacillus subtilis significantly diminished S aureus at the main intestinal colonisation site via specific bacterial interaction in mice; in this study, we tested this probiotic approach to control S aureus colonisation in humans.
We did a single-centre, phase 2, double-blind, randomised, placebo-controlled trial in adults from the Songkhla region of Thailand who were colonised by S aureus. Eligible participants were adults (aged ≥18 years) without history of intestinal disease, antibiotic treatment, or hospital admission within the previous 90 days. Participants were excluded if they were pregnant, breastfeeding, taking probiotics, or had diarrhoea. Participants were allocated (1:1) to groups by computer randomisation in blocks of four, and research coordinators were masked to group allocation. Participants received 250 mg of probiotic B subtilis MB40 or placebo once per day for 30 days and S aureus colonisation was determined after the last dose was received. The primary outcome was colonisation by S aureus (continuous, mean decrease in colony-forming-unit count) in the intestine (by faecal counts) and nares (by nasal swabs) after intervention (30-day regimen of B subtilis probiotic). This trial is registered with the Thai Clinical Trials Registry, TCTR20210128003.
The trial was done between Jan 29 and June 30, 2021, with enrolment taking place from Jan 29 to April 6, 2021. 115 participants were colonised by S aureus, either in the intestine (n=84), nose (n=50), or both (n=19), and were randomly assigned to treatment (n=55) and placebo groups (n=60). Oral probiotic B subtilis resulted in significant reduction of S aureus in stool (96·8%; p<0·0001) and nose (65·4%; p=0·0002). There were no differences in adverse effects or significant microbiome changes between the intervention and placebo groups.
B subtilis probiotic eliminated more than 95% of the total S aureus colonising the human body without altering the microbiota. This probiotic strategy offers several key advantages over presently used decolonisation strategies for potential use in people with chronic or long-term risk of S aureus infection. Furthermore, by establishing a defining role of the intestinal colonisation site, our findings call for revisiting fundamental notions about S aureus colonisation.
National Research Council of Thailand and US National Institutes of Health.
去殖民化被认为是降低金黄色葡萄球菌感染率的一种有效手段。然而，之前针对鼻子或皮肤的局部策略收效甚微，而基于口服抗生素的去殖民化方法也不可取，因为这会消灭微生物群并导致抗生素耐药性的产生。我们之前的研究表明，枯草芽孢杆菌通过在小鼠的主要肠道定植部位进行特定的细菌相互作用，显著降低了金黄色葡萄球菌的定植；在这项研究中，我们测试了这种益生菌方法来控制人类金黄色葡萄球菌的定植。
我们在泰国 Songkhla 地区进行了一项单中心、2 期、双盲、随机、安慰剂对照试验，纳入了金黄色葡萄球菌定植的成年人。符合条件的参与者为年龄≥18 岁、无肠道疾病史、抗生素治疗史或入院史（90 天内）的成年人。排除标准包括孕妇、哺乳期妇女、服用益生菌或腹泻的参与者。参与者按 1:1 比例通过计算机随机分组，分为 4 个块，研究协调员对分组情况设盲。参与者每天接受 250mg 枯草芽孢杆菌 MB40 或安慰剂，共 30 天，在最后一次给药后确定金黄色葡萄球菌定植情况。主要结局为肠道（通过粪便计数）和鼻腔（通过鼻拭子）金黄色葡萄球菌定植（连续，菌落形成单位计数的平均减少）在干预后（枯草芽孢杆菌益生菌 30 天疗程）。该试验在泰国临床试验注册中心注册，注册号为 TCTR20210128003。
试验于 2021 年 1 月 29 日至 6 月 30 日进行，入组时间为 2021 年 1 月 29 日至 4 月 6 日。共有 115 名参与者的肠道（n=84）、鼻腔（n=50）或两者（n=19）被金黄色葡萄球菌定植，他们被随机分配到治疗组（n=55）和安慰剂组（n=60）。口服枯草芽孢杆菌导致粪便中金黄色葡萄球菌的显著减少（96.8%；p<0.0001）和鼻腔（65.4%；p=0.0002）。干预组和安慰剂组之间在不良反应或显著的微生物组变化方面无差异。
枯草芽孢杆菌益生菌消除了超过 95%定植于人体的金黄色葡萄球菌，而不会改变微生物群。与目前用于慢性或长期金黄色葡萄球菌感染风险人群的去殖民化策略相比，这种益生菌策略具有几个关键优势。此外，通过确定肠道定植部位的定义作用，我们的研究结果呼吁重新审视关于金黄色葡萄球菌定植的基本概念。
泰国国家研究理事会和美国国立卫生研究院。
