Vigsnaes Louise Kristine, Ghyselinck Jonas, Van den Abbeele Pieter, McConnell Bruce, Moens Frédéric, Marzorati Massimo, Bajic Danica
Glycom A/S-DSM Nutritional Products Ltd., Kogle Allé 4, DK-2970 Hørsholm, Denmark.
Department of Technology, Faculty of Health, University College Copenhagen, DK-2200 Copenhagen, Denmark.
Pathogens. 2021 Jul 22;10(8):927. doi: 10.3390/pathogens10080927.
(formerly ) infection (CDI) is one of the most common hospital-acquired infections, which is often triggered by a dysbiosed indigenous gut microbiota (e.g., upon antibiotic therapy). Symptoms can be as severe as life-threatening colitis. The current study assessed the antipathogenic potential of human milk oligosaccharides (HMOs), i.e., 2'-O-fucosyllactose (2'FL), lacto-N-neotetraose (LNnT), and a combination thereof (MIX), against ATCC 9689 using in vitro gut models that allowed the evaluation of both direct and, upon microbiota modulation, indirect effects. During a first 48 h fecal batch study, dysbiosis and CDI were induced by dilution of the fecal inoculum. For each of the three donors tested, levels strongly decreased (with >4 log CFU/mL) upon treatment with 2'FL, LNnT and MIX versus untreated blanks, coinciding with increased acetate/ levels. Interindividual differences among donors at an intermediate time point suggested that the antimicrobial effect was microbiota-mediated rather than being a direct effect of the HMOs. During a subsequent 11 week study with the Pathogut model (specific application of the Simulator of the Human Intestinal Microbial Ecosystem (SHIME)), dysbiosis and CDI were induced by clindamycin (CLI) treatment. Vancomycin (VNC) treatment cured CDI, but the further dysbiosis of the indigenous microbiota likely contributed to CDI recurrence. Upon co-supplementation with VNC, both 2'FL and MIX boosted microbial activity (acetate and to lesser extent propionate/butyrate). Moreover, 2'FL avoided CDI recurrence, potentially because of increased secondary bile acid production. Overall, while not elucidating the exact antipathogenic mechanisms-of-action, the current study highlights the potential of HMOs to combat CDI recurrence, help the gut microbial community recover after antibiotic treatment, and hence counteract the adverse effects of antibiotic therapies.
（以前称为）艰难梭菌感染（CDI）是最常见的医院获得性感染之一，通常由肠道微生物群失调（例如在抗生素治疗后）引发。症状可能严重到危及生命的结肠炎。当前研究使用体外肠道模型评估了人乳寡糖（HMOs），即2'-O-岩藻糖基乳糖（2'FL）、乳糖-N-新四糖（LNnT）及其组合（MIX）对ATCC 9689的抗致病潜力，该模型能够评估直接作用以及在微生物群调节后的间接作用。在第一个48小时的粪便批次研究中，通过稀释粪便接种物诱导微生物群失调和CDI。对于测试的三个供体中的每一个，与未处理的空白相比，用2'FL、LNnT和MIX处理后， 水平大幅下降（>4 log CFU/mL），同时乙酸盐/ 水平升高。供体在中间时间点的个体差异表明，抗菌作用是由微生物群介导的，而不是HMOs的直接作用。在随后使用Pathogut模型（人类肠道微生物生态系统模拟器（SHIME）的特定应用）进行的11周研究中，通过克林霉素（CLI）治疗诱导微生物群失调和CDI。万古霉素（VNC）治疗治愈了CDI，但本地微生物群的进一步失调可能导致CDI复发。与VNC共同补充时，2'FL和MIX均增强了微生物活性（乙酸盐以及程度较轻的丙酸盐/丁酸盐）。此外，2'FL避免了CDI复发，这可能是由于次级胆汁酸产量增加。总体而言，虽然目前的研究没有阐明确切的抗致病作用机制，但突出了HMOs对抗CDI复发、帮助肠道微生物群落抗生素治疗后恢复以及抵消抗生素治疗不良反应的潜力。
