Pharmacokinetics of Probiotics and Biotherapeutic Agents in Humans

Abstract

Probiotics or biotherapeutic agents can influence physiology through direct or indirect effects occurring in the gastrointestinal tract. Knowledge on their pharmacokinetics is needed 1) to answer the questions how much probiotic should be consumed?, how often?, how long?; 2) to correlate the effects with the concentration of the probiotic at the target site; 3) to validate hypotheses such as "a probiotic should be of human origin, ... have a high survival capacity, ... adhere to the intestinal epithelium" ...; 4) to anticipate the effects of other probiotics; 5) to establish what concentrations should be present in the commercial preparations; 6) for safety. Some in vitro models have been developed to predict the survival of probiotics in vivo or their adherence to the intestinal epithelium, however, the best way to establish the pharmacokinetics of a probiotic is to measure it in vivo. Three techniques can be used: collection of feces, pixigraphy, and intestinal intubation. The use of transit markers such as spores of Bacillus stearothermophilus is necessary to study the potential for probiotics to colonize (i.e. to persist for longer period than the inert marker). Knowledge on the pharmacokinetics of probiotics is reviewed. Some strains can adhere to cell lines such as CaCo2 or HT29. The survival of ingested probiotics differs greatly between genus and strains. Some strains are rapidly destroyed in the stomach while others such as some Bifidobacterium sp. or Lactobacillus sp. survive till feces.

Pharmacokinetics of Lactobacillus plantarum NCIMB 8826, Lactobacillus fermentum KLD, and Lactococcus lactis MG 1363 in the human gastrointestinal tract

“…It did not colonize the gut, but persisted throughout the 1‐week period of administration. Studies assessing the survival of ingested microorganisms in the gastrointestinal tract are important in the development of oral vaccines or probiotics 6 . Comparisons of strains may sometimes be difficult because of slight differences in the recovery from the chyme, which may be partly influenced by culture techniques.…”

“…Peyer’s patches, which are mainly located in the terminal ileum. Few lactic acid bacteria strains have been studied for their pharmacokinetics in the gastrointestinal tract, which is known to vary from strain to strain 6 . In vitro techniques have been proposed for this purpose, 7 –9 but the most relevant information is that obtained in vivo .…”

Kinetics ofLactobacillus plantarum44a in the faeces of tilapia (Oreochromis niloticus) after its intake in feed

“…As a constraint, the pulse signal should be above the detection level to quantify the viability of the bacteria ingested within the host. In general, most of probiotic bacteria are excreted after ingestion (Marteau and Vesa 1998). The indigenous gastrointestinal microbiota acts as an integral defense against the colonization of orally introduced microbes.…”

Probiotics in clinical conditions

“…A pharmacological approach was used to assess the positive effects and potential side effects of the products as well as their pharmacokinetics (2,4). The level of evidence for efficacy can be assessed with the rules of evidence-based medicine.…”

“…The level of evidence for efficacy can be assessed with the rules of evidence-based medicine. We now know that the stability of many products (but not all) is good (5), that many strains (but not all) survive in the gastrointestinal tract (4), and that many double-blind randomized controlled trials (RCT) reported that some probiotics were more efficient than a placebo or a control treatment in specific clinical situations. The effects can be direct or indirect through modulation of the endogenous flora or of the immune system (2).…”