WHAT ARE PROBIOTICS ?
Probiotics are nowadays defined as live bacteria that may confer a health benefit on the host. Since the term was first introduced in 1953 and defined as microbial derived factors that stimulate the growth of other microorganisms, its definition has been constantly adjusted in regards to latest scientific findings. At the beginning of the 20th century, Russian scientist and Nobel laureate Elie Metchnikoff, professor at the Pasteur Institute in Paris, first observed the beneficial role played by certain bacteria and hence suggested that useful microbes might be able to modify the gut flora by replacing harmful ones. At the same time, another researcher from the Pasteur Institute, Henry Tissier, first isolated Bifidobacteria and clinically observed benefits of their administration in the treatment of diarrhea in infants.
Since the discovery of probiotics, many assumptions have been made on their beneficial effects on health, triggering the development and marketing of numerous dairy products enriched with probiotics. However, those effects have been put into question lately, leading to many controversies about safety and evidence-based health claims on probiotics.
So far, all health claims submitted to the European Food Safety Authority (EFSA) were considered as lacking sufficient scientific evidence to prove a cause and effect relationship between consumption of probiotic products and any health benefit. However, the rapidly growing interest that researchers have lately been showing toward microbiota has been boosting a series of new studies.
MICROBIOTA AND NUTRIGENOMICS RESARCH
The importance of the role played by microbiota (read our expert opinion article) in genome-nutrients interactions has recently been discussed by Kang J.X., researcher at the Massachusetts General Hospital and Harvard Medical School of Boston, USA, in the editorial of the latest issue of the Journal of Nutrigenetics and Nutrigenomics (1).
The latest findings about the interplay between gut bacteria and effects of dietary nutrients on gene expression “illustrate a new interface for the regulation of gene expression by dietary nutrients, and also reveal an alternative pathway for regulating gene expression through the manipulation of the gut microbiota, “ says Dr. Kang.
“Specifically, we need to understand which nutrients can increase the beneficial bacteria and which can suppress the harmful bacteria, so that we can formulate dietary regimens and food products that can be used to normalize gut microbial composition,” he added.
STATE OF RESEARCH ON PROBIOTICS
Alterations in the gut microbiota as a result of probiotics are widely acknowledged but evidence showing that probiotic administration directly affects health in human is still lacking consistency. There are some reports in the literature indicating possible anti-obesity effects of probiotic bacteria, although the underlying mechanisms have not been revealed. Studies in humans suggest a decrease in adiposity in obese individuals. However it is mostly in animal studies that the administration of specific probiotics has been shown to reduce obesity, insulin resistance, and glucose intolerance (reviewed in (2)).
Obesity is now recognized as a mild or low-grade chronic inflammation state. In this regard, there are some recent studies that provided evidence of a direct effect of probiotic administration on inflammatory states (3, 4). One possible mechanism of action involves alteration of gut epithelium permeability, a key mechanism in immunity and inflammation. Indeed, in a recent study, alteration of the population of bifidobacteria through prebiotics (non-digestible food ingredients able to specifically stimulate the growth or activity of some gut bacteria) was able to modulate inflammatory response (5). Still, the authors warned that « whether the oral application of exogenous bifidobacteria could help improve symptoms of the metabolic syndrome needs to be investigated”.
Moreover, a series of animal studies described antidiabetic effects of probiotic administration (reviewed in (6)). These interesting studies, however, do not predict what might happen in humans and failed to directly assess the relationship between the observed metabolic changes and the gut microbiota composition.
During the first half of 2013, interesting studies about beneficial effect of probiotics in different areas have been published. One of them, published in Neuroscience, suggests that probiotics may improve the cognitive functions of animals with diabetes (7). Their ability to ease diarrhea and other problems associated with antibiotic use in some patients has also gained strength through systematic review and meta-analysis conducted by researchers of the University of Toronto (8). Furthermore, another study published in the Journal of Clinical Investigation showed that probiotic/prebiotic supplementation of antiretrovirals improves gastrointestinal immunity in SIV-infected macaques, suggesting that pre- and probiotics might provide an exciting, well tolerated and cost-effective adjunctive therapeutic approach for HIV infection by enhancing gastrointestinal immune function (9).
Finally, a study published last April in The Journal of Clinical Endocrinology & Metabolism reported the first human study demonstrating that an oral probiotic supplement significantly increased Vitamin D gut absorption, and thus resulted in increased circulating levels in the blood (10). Vitamin D, also called the sunshine vitamin, plays a role in calcium fixation in the bones and is an important signaling molecule involved in inflammation, immune, and neuromuscular functions. It counts among the top 5 most popular food supplements. Leader author of the study, Dr Mitchell Jones, is Scientific Chief Officer of Micropharma, a Canadian biotechnology company that discovers and commercializes novel products based on the human microbiome for the diagnosis and treatment of metabolic diseases. The company, which is partly owned by the French diary giant Groupe Danone, has already published data on the cholesterol lowering activity of the same probiotic strain (11).
Newest outbreak in the field is Spanish firm Biosearch Life patent application for the tumor treating potential of Bifidobacterium probiotics infused with magnetic nano metals (see article in Nutraingredients.com). This technology, which has been developed since 2011 in collaboration with the University of Granada, enables the incorporation of nano particles into bacteria, thus making them visible by Nuclear Magnetic Resonance Imaging. Applications concerns tumor detection and treatment, as well as increased intake of supplemented minerals, such as zinc, selenium, iron and calcium.
1. Kang JX (2013) Gut microbiota and personalized nutrition. J Nutrigenet Nutrigenomics 6: I-II 2. Krznaric Z, Vranesic Bender D, Kunovic A, Kekez D and Stimac D (2012) Gut microbiota and obesity. Dig Dis 30: 196-200 3. Konstantinov SR, Smidt H, de Vos WM, Bruijns SC, Singh SK, Valence F, Molle D, Lortal S, Altermann E, Klaenhammer TR and van Kooyk Y (2008) S layer protein A of Lactobacillus acidophilus NCFM regulates immature dendritic cell and T cell functions. Proceedings of the National Academy of Sciences of the United States of America 105: 19474-9 4. van Baarlen P, Troost FJ, van Hemert S, van der Meer C, de Vos WM, de Groot PJ, Hooiveld GJ, Brummer RJ and Kleerebezem M (2009) Differential NF-kappaB pathways induction by Lactobacillus plantarum in the duodenum of healthy humans correlating with immune tolerance. Proceedings of the National Academy of Sciences of the United States of America 106: 2371-6 5. Blaut M and Bischoff SC (2010) Probiotics and obesity. Ann Nutr Metab 57 Suppl: 20-3 6. Kootte RS, Vrieze A, Holleman F, Dallinga-Thie GM, Zoetendal EG, de Vos WM, Groen AK, Hoekstra JB, Stroes ES and Nieuwdorp M (2012) The therapeutic potential of manipulating gut microbiota in obesity and type 2 diabetes mellitus. Diabetes Obes Metab 14: 112-20 7. Davari S, Talaei SA, Alaei H and Salami M (2013) Probiotics treatment improves diabetes-induced impairment of synaptic activity and cognitive function: behavioral and electrophysiological proofs for microbiome-gut-brain axis. Neuroscience 240: 287-96 8. Pattani R, Palda, V.A., Hwang, S. W., Prakeshkumar S.S. (2013) Probiotics for the prevention of antibiotic-associated diarrhea and Clostridium difficile infection among hospitalized patients: systematic review and meta-analysis Open Medicine 7: 9. Klatt NR, Canary LA, Sun X, Vinton CL, Funderburg NT, Morcock DR, Quinones M, Deming CB, Perkins M, Hazuda DJ, Miller MD, Lederman MM, Segre JA, Lifson JD, Haddad EK, Estes JD and Brenchley JM (2013) Probiotic/prebiotic supplementation of antiretrovirals improves gastrointestinal immunity in SIV-infected macaques. J Clin Invest 123: 903-7 10. Jones ML, Martoni CJ and Prakash S (2013) Oral supplementation with probiotic L. reuteri NCIMB 30242 increases mean circulating 25-hydroxyvitamin D: a post-hoc analysis of a randomized controlled trial. J Clin Endocrinol Metab 98: 2944-2951 11. Jones ML, Martoni CJ and Prakash S (2012) Cholesterol lowering and inhibition of sterol absorption by Lactobacillus reuteri NCIMB 30242: a randomized controlled trial. European journal of clinical nutrition 66: 1234-41