Are Probiotic Effects Dose-Related?

Abstract

Probiotics are increasingly used in order to help prevent or treat a growing number of conditions, especially gastrointestinal tract disorders. Indeed, a large number of clinical trials, many properly randomized and controlled, have shown significant efficacy in a number of gastrointestinal conditions. However, studies have been very heterogeneous and conclusions are often hard to draw. An issue which has been grossly neglected appears to be that of pharmacokinetics. In fact, studies addressing any type of dose-effect relationship are extremely limited, and drawing conclusions on the relationship between dose and effect for any probiotic species in the context of any specific disorder is close to impossible. This chapter analyzes the available evidence on this aspect, looking at areas such as acute infectious diarrhea, prevention of antibiotic-associated diarrhea, necrotizing enterocolitis, and irritable bowel syndrome. As we acknowledge the paucity of data available on the pharmacokinetics of probiotics and aim to understand more about their mechanisms of action, caution must also be exerted on possible unsafe levels. It is evident that much more solid evidence needs to be provided on the dose-effect relationship of probiotics by analyzing single preparations in rigorously controlled studies that must also aim at establishing possible unsafe or risky levels.A recent survey among physicians in the UK [1] showed that 70% of respondents recommended or prescribed probiotics to their patients, including 53% of surgeons and 80% of gastroenterologists. The most popular indications were irritable bowel syndrome (IBS; 70% of prescribers) and pouchitis (67% of prescribers). Yet, this enthusiasm for probiotics, which is likely to be worldwide and in large part based on the vast amount of data that has accumulated over the past decade or two, does not appear to be based on a sound understanding of their pharmacokinetics, which remains poorly understood.In 2001, an expert group of the WHO/FAO defined probiotics as 'live microorganisms that when administered in adequate amounts confer a health benefit on the host' [2]. Thus, it is already apparent that in such a definition, which is currently widely accepted by experts in the field, the existence of a dose-effect relationship ('in adequate amounts') is implied as relevant to the health benefit. In spite of this, very scanty data are available that investigate such a relationship, notwithstanding an enormous

Side Effects Associated with Probiotic Use in Adult Patients with Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

“…In the two previous studies probiotics were taken for years, whereas in the RCTs included in our meta-analysis they were taken for a maximum of one year [32,33]. In general, it is an increasingly accepted concept that probiotic benefits may be dose-dependent, only manifesting themselves upon achievement of a threshold dosage [42]. Probiotic amounts in currently used formulations show a wide variability, ranging from 10 7 to 10 11 CFU/g, which likely implies a high variability in the number of viable cells included in the products.…”

“…Probiotic amounts in currently used formulations show a wide variability, ranging from 10 7 to 10 11 CFU/g, which likely implies a high variability in the number of viable cells included in the products. It has been ascertained that the percentage of live cells capable of driving an effective change in fecal microbiota can vary from 1% to 92% [42]. We can assume that only formulations with a high bacterial load may exert a positive effect, while those with a low bacterial content have no effect or are even contrary to expectation.…”