Fang Xin, Monk Jonathan M, Mih Nathan, Du Bin, Sastry Anand V, Kavvas Erol, Seif Yara, Smarr Larry, Palsson Bernhard O
Department of Bioengineering, University of California San Diego, 9500 Gilman Drive, La Jolla, 92093, CA, USA.
Department of Bioinformatics and Systems Biology, University of California San Diego, 9500 Gilman Drive, La Jolla, 92093, CA, USA.
BMC Syst Biol. 2018 Jun 11;12(1):66. doi: 10.1186/s12918-018-0587-5.
Escherichia coli is considered a leading bacterial trigger of inflammatory bowel disease (IBD). E. coli isolates from IBD patients primarily belong to phylogroup B2. Previous studies have focused on broad comparative genomic analysis of E. coli B2 isolates, and identified virulence factors that allow B2 strains to reside within human intestinal mucosa. Metabolic capabilities of E. coli strains have been shown to be related to their colonization site, but remain unexplored in IBD-associated strains.
In this study, we utilized pan-genome analysis and genome-scale models (GEMs) of metabolism to study metabolic capabilities of IBD-associated E. coli B2 strains. The study yielded three results: i) Pan-genome analysis of 110 E. coli strains (including 53 isolates from IBD studies) revealed discriminating metabolic genes between B2 strains and other strains; ii) Both comparative genomic analysis and GEMs suggested that B2 strains have an advantage in degrading and utilizing sugars derived from mucus glycan, and iii) GEMs revealed distinct metabolic features in B2 strains that potentially allow them to utilize energy more efficiently. For example, B2 strains lack the enzymes to degrade amadori products, but instead rely on neighboring bacteria to convert these substrates into a more readily usable and potentially less sought after product.
Taken together, these results suggest that the metabolic capabilities of B2 strains vary significantly from those of other strains, enabling B2 strains to colonize intestinal mucosa.The results from this study motivate a broad experimental assessment of the nutritional effects on E. coli B2 pathophysiology in IBD patients.
大肠杆菌被认为是炎症性肠病（IBD）的主要细菌诱因。来自IBD患者的大肠杆菌分离株主要属于B2系统发育群。先前的研究集中于对大肠杆菌B2分离株进行广泛的比较基因组分析，并确定了使B2菌株能够在人肠道黏膜中生存的毒力因子。已表明大肠杆菌菌株的代谢能力与其定殖位点有关，但在IBD相关菌株中尚未得到探索。
在本研究中，我们利用泛基因组分析和代谢的基因组规模模型（GEMs）来研究IBD相关大肠杆菌B2菌株的代谢能力。该研究产生了三个结果：i）对110株大肠杆菌（包括53株来自IBD研究的分离株）进行的泛基因组分析揭示了B2菌株与其他菌株之间有区别的代谢基因；ii）比较基因组分析和GEMs均表明，B2菌株在降解和利用源自黏液聚糖的糖类方面具有优势；iii）GEMs揭示了B2菌株中独特的代谢特征，这些特征可能使它们能够更有效地利用能量。例如，B2菌株缺乏降解阿马多里产物的酶，而是依赖邻近细菌将这些底物转化为更易于利用且可能不太受关注的产物。
综上所述，这些结果表明B2菌株的代谢能力与其他菌株有显著差异，使B2菌株能够在肠道黏膜定殖。本研究结果促使对营养对IBD患者大肠杆菌B2病理生理学的影响进行广泛的实验评估。
