Alimentary Pharmabiotic Centre, University College Cork, Western Road, Cork, Ireland.
Gut Pathog. 2009 Nov 23;1(1):19. doi: 10.1186/1757-4749-1-19.
Gastrointestinal disease is a major cause of morbidity and mortality worldwide each year. Treatment of chronic inflammatory gastrointestinal conditions such as ulcerative colitis and Crohn's disease is difficult due to the ambiguity surrounding their precise aetiology. Infectious gastrointestinal diseases, such as various types of diarrheal disease are also becoming increasingly difficult to treat due to the increasing dissemination of antibiotic resistance among microorganisms and the emergence of the so-called 'superbugs'. Taking into consideration these problems, the need for novel therapeutics is essential. Although described for over a century probiotics have only been extensively researched in recent years. Their use in the treatment and prevention of disease, particularly gastrointestinal disease, has yielded many successful results, some of which we outline in this review. Although promising, many probiotics are hindered by inherent physiological and technological weaknesses and often the most clinically promising strains are unusable. Consequently we discuss various strategies whereby probiotics may be engineered to create designer probiotics. Such innovative approaches include; a receptor mimicry strategy to create probiotics that target specific pathogens and toxins, a patho-biotechnology approach using pathogen-derived genes to create more robust probiotic stains with increased host and processing-associated stress tolerance profiles and meta-biotechnology, whereby, functional metagenomics may be used to identify novel genes from diverse and vastly unexplored environments, such as the human gut, for use in biotechnology and medicine.
胃肠道疾病每年在全球范围内都是导致发病率和死亡率的主要原因。由于慢性炎症性胃肠道疾病（如溃疡性结肠炎和克罗恩病）的确切病因尚不清楚，因此治疗这些疾病具有一定难度。由于微生物对抗生素耐药性的传播不断增加以及所谓的“超级细菌”的出现，各种类型的腹泻病等传染性胃肠道疾病也越来越难以治疗。考虑到这些问题，新型疗法的需求至关重要。尽管益生菌已经被描述了一个多世纪，但直到近年来才对其进行了广泛的研究。它们在治疗和预防疾病（尤其是胃肠道疾病）方面的应用取得了许多成功的结果，其中一些我们在本综述中概述。尽管前景广阔，但许多益生菌受到固有生理和技术弱点的限制，而且通常最具临床应用前景的菌株无法使用。因此，我们讨论了各种策略，通过这些策略可以对益生菌进行工程改造，从而创造出设计益生菌。这些创新方法包括：受体模拟策略，用于针对特定病原体和毒素的益生菌；利用病原体衍生基因的病理生物技术方法，用于创建具有更高宿主和处理相关压力耐受性的更稳健益生菌菌株；元生物技术，通过功能宏基因组学可以从各种广泛未开发的环境（如人类肠道）中鉴定出用于生物技术和医学的新型基因。
