Human Microbiome Research Program, Faculty of Medicine, University of Helsinki, 00290 Helsinki, Finland.
Translational Genomics Research Institute, Pathogen and Microbiome Division, Flagstaff, AZ 86001, USA.
Nutrients. 2020 Mar 27;12(4):935. doi: 10.3390/nu12040935.
Altered intestinal microbiota is associated with systemic and intestinal diseases, such as inflammatory bowel disease (IBD). Dysbiotic microbiota with enhanced proinflammatory capacity is characterized by depletion of anaerobic commensals, increased proportion of facultatively anaerobic bacteria, as well as reduced diversity and stability. In this study, we developed a high-throughput in vitro screening assay to isolate intestinal commensal bacteria with anti-inflammatory capacity from a healthy fecal microbiota transplantation donor. Freshly isolated gut bacteria were screened for their capacity to attenuate lipopolysaccharide (LPS)-induced interleukin 8 (IL-8) release from HT-29 cells. The screen yielded a number of and isolates, which were identified as , , , , , and using whole genome sequencing. We observed that a cell-cell contact with the epithelium was not necessary to alleviate in vitro inflammation as spent culture media from the isolates were also effective and the anti-inflammatory action did not correlate with the enterocyte adherence capacity of the isolates. The anti-inflammatory isolates also exerted enterocyte monolayer reinforcing action and lacked essential genes to synthetize hexa-acylated, proinflammatory lipid A, part of LPS. Yet, the anti-inflammatory effector molecules remain to be identified. The strains isolated and characterized in this study have potential to be used as so-called next-generation probiotics.
肠道微生物群的改变与全身性和肠道疾病有关，如炎症性肠病（IBD）。具有增强促炎能力的失调微生物群的特征是厌氧共生菌减少，兼性厌氧菌比例增加，以及多样性和稳定性降低。在这项研究中，我们开发了一种高通量的体外筛选检测方法，从健康的粪便微生物群移植供体中分离具有抗炎能力的肠道共生细菌。从新鲜分离的肠道细菌中筛选其减弱脂多糖（LPS）诱导 HT-29 细胞白细胞介素 8（IL-8）释放的能力。筛选产生了许多和 分离株，通过全基因组测序鉴定为 、 、 、 、 、 和 。我们观察到，与上皮细胞的细胞间接触对于减轻体外炎症并不是必需的，因为分离株的废弃培养物也有效，抗炎作用与分离株的肠上皮细胞黏附能力无关。抗炎分离株还发挥肠上皮细胞单层强化作用，并且缺乏合成六酰化、促炎脂质 A 的必需基因，脂质 A 是 LPS 的一部分。然而，抗炎效应分子仍有待确定。本研究中分离和表征的 菌株具有作为所谓的下一代益生菌的潜力。
