View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Springer - Publisher Connector Antonie van Leeuwenhoek (2014) 106:141–156 DOI 10.1007/s10482-014-0171-y INVITED REVIEW Antonie van Leeuwenhoek 80th Anniversary Issue Impact of genomics on the field of probiotic research: historical perspectives to modern paradigms Brant R. Johnson • Todd R. Klaenhammer Received: 22 January 2014 / Accepted: 4 April 2014 / Published online: 20 April 2014 Ó The Author(s) 2014. This article is published with open access at Springerlink.com Abstract For thousands of years, humans have Introduction safely consumed microorganisms through fermented foods. Many of these bacteria are considered probi- History of probiotic bacteria and the probiotic otics, which act through diverse mechanisms to concept confer a health benefit to the host. However, it was not until the availability of whole-genome sequen- A multitude of autochthonous (naturally occurring) cing and the era of genomics that mechanisms of commensal bacterial species inhabit the mucosal probiotic efficacy could be discovered. In this review, surfaces of the gastro-intestinal tract (GIT), as well we explore the history of the probiotic concept and the as those of the nose, mouth and vagina. It has long current standard of integrated genomic techniques to been held that the consumption of allochthonous discern the complex, beneficial relationships between (transient) beneficial bacteria, either through food probiotic microbes and their hosts. products or supplements, has a positive influence on general health and well-being of the host via com- Keywords Probiotic Á Lactic acid bacteria Á mensal interactions with the GIT immune system and Fermentation Á Genomics Á Lactobacilli Á resident microbiota. These beneficial microorganisms, Bifidobacteria known as probiotics, are defined by the World Health Organization as ‘‘live microorganisms, which when administered in adequate amounts, confer a health benefit upon the host’’ (FAO/WHO 2002). Over the past four decades, there has been substantial research in the field of probiotics and, more specifically, into the mechanism of probiotic action within the host. However, the probiotic concept is not novel to the twentieth century and twenty-first centuries. & B. R. Johnson Á T. R. Klaenhammer ( ) For millennia, humans have consumed microor- Department of Microbiology, North Carolina State University, Raleigh, NC, USA ganisms via fermented foods, which served to prevent e-mail: [email protected] putrefaction as well as increase sensory aspects in the food. Some of the first fermentations were likely the T. R. Klaenhammer result of serendipitous contaminations in favourable Department of Food, Bioprocessing, and Nutrition Science, North Carolina State University, Raleigh, NC, environments resulting in soured milk products such USA as kefir, leben, koumiss, yogurt and sour cream— 123 142 Antonie van Leeuwenhoek (2014) 106:141–156 products that are still consumed worldwide (Hosono microorganisms may act as anti-putrefactive agents 1992). Furthermore, through the continued practice of in the gastrointestinal tract when consumed. In fact, he milk souring along with back slopping techniques, hypothesized that by transforming the ‘‘wild popula- humans inadvertently aided in the domestication of tion of the intestine into a cultured population… the certain microorganisms to diverse food environments pathological symptoms may be removed from old age, over time (Douglas and Klaenhammer 2010). Not only and… in all probability, the duration of the life of man were these products safe to consume, fermented dairy may be considerably increased’’ (Metchnikoff 1907). foods were culturally significant, as evidenced by their His theory was bolstered upon observing a higher mention in the Bible and early sacred Hindu texts, as prevalence of centenarians in Bulgaria, a region well as therapeutically consumed (Hosono 1992; Bibel known for the consumption of soured milk. Michel 1988; Shortt 1999). Cohendy, a colleague at the Pasteur Institute, provided In the late nineteenth century, French biochemist experimental data to support Metchnikoff’s hypothe- Louis Pasteur premiered significant discoveries lead- sis. In two feeding trials of human subjects, Cohendy ing to a greater scientific understanding of fermenta- found that the Bulgarian bacillus (now known as tion (Fig. 1). Upon studying wine and beer Lactobacillus delbrueckii subsp. bulgaricus) was fermentations, Pasteur demonstrated that fermentation recoverable from faeces; reduced the prevalence of reactions are carried out by microorganisms. Further- putrefactive toxins; and aided in the treatment of more, he established that the growth of these microbes colitis following transplantation to the large intestine is not a product of spontaneous generation, as was the (Cohendy 1906a, b). The aforementioned studies on L. prevailing scientific and cultural consensus, but is bulgaricus enthralled the health-conscious society of instead due to biogenesis, which posits that all living Europe in the early 20th century and soon the Pasteur things come only from other living things. On the Institute of Paris began selling the Lactobacillus under foundation of Pasteur’s research, Russian Nobel the label of ‘‘Le Ferment’’ (Shortt 1999; Bibel 1988). laureate, E´ lie Metchnikoff first popularized the con- Despite the promising observations made by cept of probiotics around the turn of the twentieth Metchnikoff and colleagues at the genesis of the century. In his book, The Prolongation of Life: probiotic concept, there was still meager scientific Optimistic Studies, Metchnikoff (1907) proposed that evidence suggesting any definitive probiotic strains or putrefaction in the intestines correlated with shortened their purported effector mechanisms. In fact, Leo life expectancy. Reconciling long-held observations Rettger and coworkers at Yale University found that L. involving lactic acid food fermentations with micro- bulgaricus could not survive gastric passage to bial feeding studies in animals and humans, Metch- colonize the small intestine (Rettger 1915). This study nikoff proposed that lactic acid-producing called into question which strain(s) may have been 1864 1915 1953 1995 2010 Louis Pasteur Leo Rettger proves that disproves spontaneous L. bulgaricus cannot The structure of DNA is First complete genome Human gut microbiome generation. First survive gastric transit. resolved. sequenced – catalogued. observes LAB in Proposes L. acidophilus Haemophilus influenzae spoiled beer. as a suitable probiotic. 1907 1930 1974 1999 – Élie Metchnikoff publishes Minoru Shirota isolates The prolongation of life: L. casei from human Introduction of Sanger Genome sequencing of Optimistic studies based on faeces. Develops and Sequencing LAB and probiotic observations of Bulgarian commercializes one of bacteria commence, peasants. Bulgarian bacillus the first fermented milk allowing for integrated sold as ‘Le ferment’ by the products, Yakult, based genomic analysis Pasteur Institute. on this isolate. Fig. 1 Seminal milestones contributing to the functional characterization of probiotic lactic acid bacteria 123 Antonie van Leeuwenhoek (2014) 106:141–156 143 present in the original therapeutic administration of scientific questions to explore concerning probiotic studies performed by Cohendy, and subsequently sold activities and interactions in the GIT, there remains a as ‘‘Le Ferment.’’ Instead, Lactobacillus acidophilus bright future for the field of probiotic research and the was touted to be a more suitable candidate for market thereof. therapeutic applications because of its ability to survive gastric passage and transform the intestinal Modern use of probiotic bacteria flora in conditions of lactose and dextrin supplemen- tation (Rettger and Cheplin 1921). It is based on these Despite the long, storied history of probiotic discovery seminal studies that the foundation of therapeutic and therapeutic application, resounding clinical and treatment with L. acidophilus originated. However, experimental evidence for the use of probiotic bacteria even rigorous studies such as these were limited by the has only recently come to a head (Table 1). One techniques and technologies of their time. L. acidoph- prominent example is the use of probiotics to treat ilus could not be distinguished from other aciduric functional gastrointestinal disorders (FGID). For commensal lactobacilli, such as Lactobacillus gasseri, many FGID, such as irritable bowel syndrome (IBS), until electrophoretic DNA–DNA hybridization studies there are few pharmacological treatment options due on Lactobacillus lactate dehydrogenase enzymes were to low efficacy and serious side effects (Shen and performed in the 1970s (Gasser 1970; Gasser et al. Nahas 2009). Furthermore, IBS is quite common and 1970). Therefore, it is unknown whether the cultures is thought to be caused by changes in the gastrointes- administered during these studies were indeed pure L. tinal microbiome (Porter et al. 2011). Recently, a acidophilus, or mixed culture with L. acidophilus, L. systematic review of successful clinical interventions gasseri and other aciduric lactobacilli. using probiotics to treat various FGID has been After examining the burgeoning experimental evi- compiled as a reference for clinicians to make dence of probiotic bacteria, a Japanese physician evidence-based treatment decisions (Hungin et al. named Minoru Shirota sought to isolate a human- 2013). This systematic analysis