Boyte Marie-Eve, Benkowski Andrzej, Pane Marco, Shehata Hanan R
NutraPharma Consulting Services Inc., Sainte-Anne-des-Plaines, QC, Canada.
Eurofins, Madison, WI, United States.
Front Microbiol. 2023 Dec 7;14:1304621. doi: 10.3389/fmicb.2023.1304621. eCollection 2023.
Probiotics are the largest non-herbal/traditional dietary supplements category worldwide. To be effective, a probiotic strain must be delivered viable at an adequate dose proven to deliver a health benefit. The objective of this article is to provide an overview of the various technologies available for probiotic enumeration, including a general description of each technology, their advantages and limitations, and their potential for the future of the probiotics industry. The current "gold standard" for analytical quantification of probiotics in the probiotic industry is the Plate Count method (PC). PC measures the bacterial cell's ability to proliferate into detectable colonies, thus PC relies on cultivability as a measure of viability. Although viability has widely been measured by cultivability, there has been agreement that the definition of viability is not limited to cultivability. For example, bacterial cells may exist in a state known as viable but not culturable (VBNC) where the cells lose cultivability but can maintain some of the characteristics of viable cells as well as probiotic properties. This led to questioning the association between viability and cultivability and the accuracy of PC in enumerating all the viable cells in probiotic products. PC has always been an estimate of the number of viable cells and not a true cell count. Additionally, newer probiotic categories such as Next Generation Probiotics (NGPs) are difficult to culture in routine laboratories as NGPs are often strict anaerobes with extreme sensitivity to atmospheric oxygen. Thus, accurate quantification using culture-based techniques will be complicated. Another emerging category of biotics is postbiotics, which are inanimate microorganisms, also often referred to as tyndallized or heat-killed bacteria. Obviously, culture dependent methods are not suitable for these products, and alternative methods are needed for their quantification. Different methodologies provide a more complete picture of a heterogeneous bacterial population versus PC focusing exclusively on the eventual multiplication of the cells. Alternative culture-independent techniques including real-time PCR, digital PCR and flow cytometry are discussed. These methods can measure viability beyond cultivability (i.e., by measuring cellular enzymatic activity, membrane integrity or membrane potential), and depending on how they are designed they can achieve strain-specific enumeration.
益生菌是全球最大的非草药/传统膳食补充剂类别。要发挥功效,益生菌菌株必须以经证实能带来健康益处的适当剂量活菌形式递送。本文的目的是概述可用于益生菌计数的各种技术,包括对每种技术的一般描述、其优点和局限性,以及它们对益生菌行业未来的潜力。益生菌行业中益生菌分析定量的当前“金标准”是平板计数法(PC)。PC测量细菌细胞增殖形成可检测菌落的能力,因此PC依赖可培养性作为活力的衡量标准。尽管活力广泛通过可培养性来衡量,但人们一致认为活力的定义不限于可培养性。例如,细菌细胞可能处于一种称为活但不可培养(VBNC)的状态,在这种状态下细胞失去可培养性,但仍能保持一些活细胞的特征以及益生菌特性。这引发了对活力与可培养性之间关联以及PC在枚举益生菌产品中所有活细胞时准确性的质疑。PC一直是对活细胞数量的估计,而非真正的细胞计数。此外,新型益生菌类别如新一代益生菌(NGP)在常规实验室中难以培养,因为NGP通常是严格厌氧菌,对大气中的氧气极其敏感。因此,使用基于培养的技术进行准确定量会很复杂。另一类新兴的生物制剂是后生元,它们是无生命的微生物,也常被称为加热灭活或热死细菌。显然,依赖培养的方法不适用于这些产品,需要替代方法对其进行定量。与仅专注于细胞最终增殖的PC相比,不同的方法能更全面地呈现异质细菌群体的情况。本文讨论了包括实时PCR、数字PCR和流式细胞术在内的替代非培养技术。这些方法可以测量超出可培养性的活力(即通过测量细胞酶活性、膜完整性或膜电位),并且根据其设计方式,它们可以实现菌株特异性计数。