Probiotics
The Role of Probiotics in Intestinal Inflammation Henri Braat, MD, PhD,1
Ernst J Kuipers, MD, PhD2
and Maikel P Peppelenbosch, PhD3
1. Gastroenterologist; 2. Professor of Gastroenterology and Hepatology; 3. Professor of Experimental Gastroenterology and Hepatology, Department of Gastroenterology and Hepatology, Erasmus Medical Center, Rotterdam
Abstract
Probiotics are frequently used food supplements and are tested in clinical trials for various diseases. Positive results from these trials are scarce while many biologic effects of probiotics on the intestinal microbiome, barrier, and immune function have been described. Apparently, a discrepancy exists between the biologic effects of probiotics and their efficacy in inflammatory bowel disease, irritable bowel syndrome, and pancreatitis. Several modifying factors, such as the use of prebiotics, microbiome composition, host immunity, and quorum effects, might negatively influence the biologic effects of probiotics. Besides, some of these probiotic effects are insignificant in terms of the entire host– microbiome interactions present in the intestinal system and not unique to probiotics alone. Still, the use of probiotics in chronic disease remains attractive due to their negligible toxicity profile. Different probiotics have been used as expression vectors for recombinant proteins and antibodies. A clinical trial has been performed with interleukin-10-producing Lactococcus lactis to prove containment of the introduced gene. Other strategies to modulate intestinal barrier and immune function have been described and genetic modification of probiotics is a promising strategy to treat intestinal inflammation.
Keywords
Intestinal inflammation, probiotics, genetic modification, intestinal barrier function, irritable bowel syndrome, inflammatory bowel disease, pancreatitis
Disclosure: The authors have no conflicts of interest to declare. Received: March 24, 2011 Accepted: June 14, 2011 Citation: US Gastroenterology & Hepatology Review, 2011;7(1):38–42 Correspondence: Henri Braat, MD, PhD, Department of Gastroenterology and Hepatology, Erasmus Medical Center, Room Hs-510, PO Box 2040, 3000 CA Rotterdam, The Netherlands. E:
h.braat@
erasmusmc.nl
Probiotics are defined as viable, non-pathogenic micro-organisms that are able to reach the intestine in sufficient viable numbers to confer benefit to the host. Although frequently used, the term probiotics is misleading as it suggests that one probiotic strain can induce multiple biologic effects that lead to a general health benefit. Besides, many of the biologic effects are not exclusive to probiotics, as commensal and/or pathogenic bacteria can have comparable effects.
A major pitfall in clinical studies with probiotics is the focus on measuring a clinical effect without studying the biologic effect of the administered probiotic strain. There is a large discordance between biologic effects and clinical effects in probiotic research due to several reasons (see Figure 1). First, a probiotic strain has limited biologic effects which might, in view of the complexity of the gastrointestinal immune system, be too insignificant to exert a robust clinical effect. Second, there is a huge diversity in gastrointestinal microbiome between individuals. Comparison of the microbiome between individuals has shown that family members have functionally more similar gut microbiome than do unrelated individuals. Consequently, the microbial environment in which a probiotic strain has to exert its effect is significantly different between unrelated individuals. As a result, probiotic effects are not universal, due to the fact that metabolic activity and biologic behavior
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of probiotic strains are dependent on the host and its microbiome. Therefore, probiotic research would benefit from genetic description of the strains used, strain selection, and controlling for the pursued biologic effect in vivo.
In this article we will describe possible biologic effects provoked by probiotic strains in health and gastrointestinal inflammatory diseases. We will discuss the possibility of improving clinical efficacy by genetic manipulation of probiotics.
The Role of Probiotics in Intestinal Biology Probiotics and the Intestinal Microbiome Probiotics are an integral part of the human microbiome, which displays a remarkable functional stability although its composition is dynamic, containing native species that occupy a continuous niche but also a variable set of transient species that only temporarily fill an empty niche.1 The human microbiome is able to influence epithelial physiology and to perform a set of biochemical processes that have evolutionarily relieved the host from evolving such functions.2
In return, the gastrointestinal
microbiome is provided with a nutrient-rich environment allowing it to inhabit a particular niche (symbiosis). The functions of the microbiome include the conversion of indigestible food constituents into, for example,
© TOUCH BRIEFINGS 2011
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