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New names for important probiotic Lactobacillus species

/in ISAPP Science Blog, News /by KC

By Mary Ellen Sanders, PhD, and Sarah Lebeer, PhD

The genus Lactobacillus was listed as the fifth most important category of living organism to have influenced the planet throughout its evolutionary history in a 2009 book, What on Earth Evolved?. From their central role in food fermentations around the globe to their ability to benefit health in their human and animal hosts, species of Lactobacillus have great importance in our lives.

But for the past several decades there’s been a problem brewing with this genus. Using the research tools available at the time, researchers through history who discovered new bacteria grouped many diverse species under the “umbrella” of the genus Lactobacillus. Since the naming of the first Lactobacillus species, Lactobacillus delbrueckii, in 1901, microbial taxonomists assigned over 250 species to this genus.

These species were a diverse group, and when DNA analysis tools became more sophisticated, many were found to be only loosely related. A consensus grew among scientific experts that, given the genetic makeup of these bacteria, the current Lactobacillus genus was too diverse and did not conform to nomenclature conventions. Moreover, it was important to split the genus into functionally relevant groups that shared certain physiological, metabolic properties and lifestyles in order to facilitate functional and ecological studies on bacteria from this genus.

To tackle this problem, 15 scientists (see below) from 12 different institutions and 7 different countries came together, applying whole genome analysis to analyze each Lactobacillus species. Their proposal, which was accepted for publication in the official journal of record for bacterial names, is that the species once contained within the Lactobacillus genus should now spread over 25 genera, including 23 novel genera (see paper link here).

Based on this polyphasic approach, the authors reclassified the genus Lactobacillus into 25 genera including the emended genus Lactobacillus, which includes host-adapted organisms that have been referred to as the L. delbrueckii group; Paralactobacillus; as well as 23 novel genera: Acetilactobacillus, Agrilactobacillus, Amylolactobacillus, Apilactobacillus, Bombilactobacillus, Companilactobacillus, Dellaglioa, Fructilactobacillus, Furfurilactobacillus, Holzapfelia, Lacticaseibacillus, Lactiplantibacillus, Lapidilactobacillus, Latilactobacillus, Lentilactobacillus, Levilactobacillus, Ligilactobacillus, Limosilactobacillus, Liquorilactobacillus, Loigolactobacilus, Paucilactobacillus, Schleiferilactobacillus, and Secundilactobacillus.

While genus names have changed in some cases, the parts of the names that indicate species were not changed. See the table below for some examples of how names of important probiotic lactobacilli have changed. Note that all new genera proposed for this group begin with the letter “L”. Thus, the ‘L.’ genus abbreviation may still be used.

Because of the importance of this genus and the implications of the name change for both science and industry, the researchers involved in this project have developed a web-based tool that makes it very easy to determine the new names of all Lactobacillus species.

Scientifically, one exciting outcome of these new taxonomic groupings is that species that are more closely related, and therefore are more likely to share physiological traits, are grouped into the same genus. This may facilitate our understanding of common mechanisms that may mediate health benefits, as described in an ISAPP consensus paper and a publication entitled “Shared mechanisms among probiotic taxa: implications for general probiotic claims”.

To date, bacteria in the group Bifidobacterium have not changed, but nomenclature changes are expected soon for this genus, too.

The Lactobacillus taxonomy changes are summarized in this ISAPP infographic for scientists and in this ISAPP infographic for consumers.

Names of important Lactobacillus probiotic species

The following chart lists the new names for some prominent Lactobacillus probiotic species. (Note: All new genera proposed for this group begin with the letter “L”, so abbreviated genus/species – such as L. rhamnosus – remain unchanged.)

 

Current name New name
Lactobacillus casei Lacticaseibacillus casei
Lactobacillus paracasei Lacticaseibacillus paracasei
Lactobacillus rhamnosus Lacticaseibacillus rhamnosus
Lactobacillus plantarum Lactiplantibacillus plantarum
Lactobacillus brevis Levilactobacillus brevis
Lactobacillus salivarius Ligilactobacillus salivarius
Lactobacillus fermentum Limosilactobacillus fermentum
Lactobacillus reuteri Limosilactobacillus reuteri
Lactobacillus acidophilus Unchanged
Lactobacillus delbrueckii subsp. bulgaricus

(aka Lactobacillus bulgaricus)

 Unchanged
Lactobacillus crispatus Unchanged
Lactobacillus gasseri Unchanged
Lactobacillus johnsonii Unchanged
Lactobacillus helveticus Unchanged

Authors

  • Jinshui Zheng, Huazhong Agricultural University, State Key Laboratory of Agricultural Microbiology, Hubei Key Laboratory of Agricultural Bioinformatics, Wuhan, Hubei, P.R. China.
  • Stijn Wittouck, Research Group Environmental Ecology and Applied Microbiology, Department of Bioscience Engineering, University of Antwerp, Antwerp, Belgium
  • Elisa Salvetti, Dept. of Biotechnology, University of Verona, Verona, Italy
  • Charles M.A.P. Franz, Max Rubner-Institut, Department of Microbiology and Biotechnology, Kiel, Germany
  • Hugh M.B. Harris, School of Microbiology & APC Microbiome Ireland, University College Cork, Co. Cork, Ireland
  • Paola Mattarelli, University of Bologna, Dept. of Agricultural and Food Sciences, Bologna, Italy
  • Paul W. O’Toole, School of Microbiology & APC Microbiome Ireland, University College Cork, Co. Cork, Ireland
  • Bruno Pot, Research Group of Industrial Microbiology and Food Biotechnology (IMDO), Vrije Universiteit Brussel, Brussels, Belgium
  • Peter Vandamme, Laboratory of Microbiology, Department of Biochemistry and Microbiology, Ghent University, Ghent, Belgium
  • Jens Walter, Department of Agricultural, Food & Nutritional Science, University of Alberta, Edmonton, Canada; Department of Biological Sciences, University of Alberta, Edmonton, Canada
  • Koichi Watanabe, National Taiwan University, Dept. of Animal Science and Technology, Taipei, Taiwan R.O.C.; Food Industry Research and Development Institute, Bioresource Collection and Research Center, Hsinchu, Taiwan R.O.C.
  • Sander Wuyts, Research Group Environmental Ecology and Applied Microbiology, Department of Bioscience Engineering, University of Antwerp, Antwerp, Belgium
  • Giovanna E. Felis, Dept. of Biotechnology, University of Verona, Verona, Italy
  • Michael G. Gänzle, Department of Agricultural, Food & Nutritional Science, University of Alberta, Edmonton, Canada; Hubei University of Technology, College of Bioengineering and Food Science, Wuhan, Hubei, P.R. China.
  • Sarah Lebeer, Research Group Environmental Ecology and Applied Microbiology, Department of Bioscience Engineering, University of Antwerp, Antwerp, Belgium.

See ISAPP’s press release on the Lactobacillus name changes here.

Researchers submit recommendations for revised Lactobacillus taxonomy

/in ISAPP Science Blog, News /by KC

By Mary Ellen Sanders PhD, Executive Science Officer, ISAPP

A team of researchers has submitted their recommendations for new classification for the heterogeneous group of species currently considered to belong to the genus Lactobacillus. The paper is under review by the International Journal of Systematic and Evolutionary Microbiology, the premier journal for bacterial taxonomy.

Three research teams that were independently working on comparative genomics and taxonomic inconsistencies among lactobacilli (see here, here, here, here, here, and here) came together to openly collaborate on this publication. These teams included scientists from Italy, Canada, Belgium, Germany, China, Ireland, and Japan.

Several species important from a commercial perspective will be impacted, including Lactobacillus casei, Lactobacillus plantarum, Lactobacillus sakei, Lactobacillus salivarius, Lactobacillus reuteri and Lactobacillus brevis. New genus names are expected for these. Lactobacillus delbrueckii, Lactobacillus acidophilus, Lactobacillus gasseri, Lactobacillus johnsonii, Lactobacillus helveticus and Pediococcus are not expected to undergo name changes. Since L. delbrueckii (which includes the subspecies L. delbrueckii subspecies bulgaricus, the yogurt starter culture) was the first Lactobacillus named, convention in naming bacterial genera requires that species from this taxonomic clade will keep the Lactobacillus name.

Driving this effort is the pressing need to apply modern phylogenetic methods to establishing relationships among the many species of Lactobacillus (see previous post). The genus Lactobacillus currently comprises more than 240 species, and has been growing rapidly for decades. In 1980, 36 Lactobacillus species were recognized. By 2012, there were 152. Scientists recognized the need to reorganize the phylogenetic assignments of this genus; they are proposing splitting the Lactobacillus genus into more than 20 genera.

Once the paper is published, the task of disseminating the message about new genus names for commercially important species will begin.

See here for a detailed article on this topic.

Defining emerging ‘biotics’

/in featured, ISAPP Science Blog /by ISAPP

By Mary Ellen Sanders PhD

From its inception, ISAPP has been committed to clarity in both the definitions and the contextual use of terms in the fields of probiotics and prebiotics fields. This is reflected in the FAO/WHO probiotic guidelines working group conducted immediately prior to the first ISAPP meeting in 2002, as well as our more recent consensus panels convened on probiotics (2013), and prebiotics (2016). We also have additional panels in progress on synbiotics (convened in May 2019 in Antwerp), fermented foods (scheduled for September) and postbiotics (scheduled for December).

A recently published paper, Emerging Health Concepts in the Probiotics Field: Streamlining the Definitions, addresses definitions of many newer terms in the ‘biotics’ arena, including probiotics, prebiotics, synbiotic, pharmabiotics, postbiotics, probioceuticals, paraprobiotics, oncobiotics, psychobiotics, and live biotherapeutic products. In my opinion, although this paper provides useful discussion of issues surrounding the proliferation of terms in the ‘biotics’ area, it falls short of providing clear direction for the field and indeed may well add to confusion by introducing unnecessary, new and poorly defined terms.

For example, the term ‘symbiotics’ is perpetuated, presumably as a synonym to synbiotic. It was a missed opportunity to clarify that the term ‘synbiotic’ is derived from the Greek root ‘syn’ meaning ‘with’ or ‘together.’ The term ‘symbiotic’ is simply incorrect, adds nothing and should be eliminated altogether.

This paper fails to advance the ISAPP consensus definition of prebiotic, published in 2017, by lead author Glenn Gibson, co-inventor of the terms ‘prebiotic’ and ‘synbiotic’. It is not clear whether the authors disagree with the ISAPP consensus definition, and if so, on what basis. They state that the ISAPP consensus definition is “the most actual definition”, the meaning of which is not clear to me, but then use an outdated definition in their summary box.

Further is the failure to acknowledge the broad scope of the definition of probiotics. Live biotherapeutic products (LBPs), which the paper states is a term that was “recently” introduced by the FDA, has been in use for over at least 15 years by the FDA’s Center for Biologics Evaluation and Research. The authors equate LBPs (which are defined as drugs) with next generation probiotics, yet these do not have to fall under the drug category any more than traditional probiotics are necessarily foods. Next generation probiotics, traditional probiotics or just probiotics can fall under numerous regulatory categories including foods, infant formulas, drugs, supplements, animal feeds, medical foods, foods for special dietary uses, and perhaps even cosmetics or medical devices. Thus, regulatory category is not stipulated by the definition, which is appropriate.

One of the difficulties with sorting through these terms is the lack of any consistent basis for defining them. Some terms, such as pharmabiotics and LBPs, are linked to specific regulatory categories. Others are defined by the nature of how they are comprised: live cells, cell components, or fermentation endproducts. Others are defined by their physiological benefit: psychobiotic, oncobiotic, immunobiotic. Even still, others are defined by their state of innovation: traditional vs. next generation probiotics. This state of affairs makes is impossible to develop a logical framework for categorizing them. Instead, we are left with a long list of substances that might be related, but have little real value. Where does it all stop? Next we will have to sift through thera/metabo/gen/retro/plas/func-biotics or any other pointless terms that can be arbitrarily slapped in front of ‘biotic.’

Certainly, there is nothing to prevent any person from coining a new term for a niche development. The many stakeholders in the broader ‘biotics’ field will, I suppose, determine any given term’s utility. I believe it would have been worthwhile for this paper to make an appeal to scientists to refrain from muddying the water by proposing new terms, and instead use existing terms with appropriate modifiers. For example, use ‘immune-active probiotic’ instead of ‘immunobiotic’, or ‘probiotic drug’ instead of ‘live biotherapeutic product.’ This approach is clearer to regulators and international organizations such as Codex Alimentarius, the US Food and Drug Administration and European Food Safety Authority. To the extent that the definitions of terms need to be clarified, I believe that the ISAPP approach, using groups of 10 or more well-known academic experts in the field reaching a consensus after extensive background search, is preferred over unilateral proclamations as delivered by this paper.

Effects of the food matrix on probiotic’s efficacy: how much should we care?

/in featured, ISAPP Science Blog /by ISAPP

By Gabriel Vinderola PhD, Researcher at the Dairy Products Institute (National Scientific and Technical Research Council – CONICET) and Associate Professor at the Food Technology and Biotechnology Department, Faculty of Chemical Engineering, National University of Litoral, Santa Fe, Argentina.

The issue of to what extent food components may affect probiotic efficacy when compared to the strain delivered as supplement has lately been the subject of debate. This is especially so in the context of the Codex Alimentarius guidelines on probiotics, presently under development.

When considering the importance of the food formulation delivering the probiotic, it’s worthwhile to keep in mind that people may get their daily probiotic together with an enormous variety of foods. For instance, one person may get the probiotic at breakfast along with a yoghurt or with cereal, whereas another person may choose to consumer a fruit juice, while a third may get the probiotic dose before a meal consisting of pasta, meat and vegetables. In those cases, the same strain can undergo gastrointestinal passage in the context of very different food exposures. Does this suggest that perhaps the specific food format is not so critical? What does research tell us?

An interesting, however in vitro, study was conducted by Grześkowiak et al. (2011). In this work, Lactobacillus rhamnosus GG was recovered from more than 12 foods and supplements and its ability to inhibit food pathogens was assessed in vitro. Authors showed that even when the inhibitory capacity was quantitatively different among isolates, the qualitative probiotic capacity of inhibiting pathogens was present in all of them. That is to say, the probiotic capacity had been retained to a somewhat greater or lesser degree, regardless the matrix.

Few human studies have measured to what extent a health endpoint changes when a probiotic is delivered in different food matrixes. For instance, Saxelin et al. (2010) showed that the administration matrix (capsules, yogurt or cheese) did not influence the faecal quantity of lactobacilli, but affected faecal counts of propionibacteria and bifidobacteria. However no health endpoint was considered in this study. Several studies demonstrate that dairy products are able to confer enhanced protection during gastrointestinal transit in in vitro settings (Vinderola et al., 2000; Sagheddu et al., 2018; da Cruz Rodrigues et al., 2019), suggesting that dairy products may be better at delivering an efficacious dose of probiotic. But again, no clinical endpoint was measured in these studies.

The first comparative study on the probiotic capacity of a strain delivered in food or supplement was reported by Isolauri et al. (1991). Authors demonstrated that Lactobacillus GG either in fermented milk or freeze-dried powder was effective in shortening the course of acute diarrhea. Later on, Meng et al. (2016) found similar patterns of immune stimulation when studying the impact of Bifidobacterium animalis subsp. lactis BB12 administration in yoghurt or capsules on the upper respiratory tract of healthy adults.

As these kinds of studies are scarce, we can look to meta-analysis where the same strain is compared for the same clinical endpoint, but in studies conducted by different groups in different matrixes. For instance, Szajewska et al. (2013) concluded that Lactobacillus GG delivered in capsules or fermented milk significantly reduced the duration of diarrhea and Urbańska et al. (2016) reported that L. reuteri DSM 17938 delivered in either capsules or infant formula reduced the duration of diarrhoea and increased the chance of cure.

In vitro studies find that survival of the probiotic delivered in different food matrices through a (simulated) gastrointestinal transit may quantitatively differ, but no matrix completely eliminates probiotic capacity. Human clinical trials comparing different matrices with a clear health endpoint are scarce, but a general conclusion seems to emerge: regardless of the food matrix, the probiotic effect is achieved.  When the data are assessed through meta-analysis, the top of the “levels of evidence” in the pyramid of evidence-based studies, the probiotic capacity exists for the same strain among different studies, conducted by different research groups, using different food matrices.

In many countries regulators require that the probiotic effect be demonstrated in the same food or supplement that will be offered to consumers. This is a conservative approach in the lack of other evidence, but it may be challenging at the same time for probiotic food development, as any new food, even similar to one already existing, may require new human clinical studies to demonstrate efficacy. This approach may raise economic and ethical concerns too, and be discouraging for the future of probiotics.

Surely additional clinical trials directly comparing effects among different delivery matrices would provide clarity on the importance of this factor to probiotic functionality. Until that time, regulators should enable probiotic food manufacturers to offer a sound scientific rationale that bio-equivalency of different matrices could be expected, and thereby circumvent the requirement need to re-conduct human clinical trials on probiotics delivered in new matrices.

 

References

da Cruz Rodrigues VC, Salvino da Silva LG, Moreira Simabuco, F, Venema K, Costa Antunes AE. Survival, metabolic status and cellular morphology of probiotics in dairy products and dietary supplement after simulated digestion. J Funct. Foods, 2019, 55, 126-134.

Grześkowiak Ł, Isolauri E, Salminen S, Gueimonde M. Manufacturing process influences properties of probiotic bacteria. Br J Nutr. 2011, 105(6):887-94.

Isolauri E, Juntunen M, Rautanen T, Sillanaukee P, Koivula T. A human Lactobacillus strain (Lactobacillus casei sp strain GG) promotes recovery from acute diarrhea in children.

Meng H, Lee Y, Ba Z, Peng J, Lin J, Boyer AS, Fleming JA, Furumoto EJ, Roberts RF, Kris-Etherton PM, Rogers CJ. Consumption of Bifidobacterium animalis subsp. lactis BB-12 impacts upper respiratory tract infection and the function of NK and T cells in healthy adults. Mol Nutr Food Res. 2016, 60(5):1161-71.

Pediatrics. 1991 , 88(1):90-7.

Sagheddu V, Elli M, Biolchi C, Lucido J, Morelli L. Impact of mode of assumption and food matrix on probiotic viability. J Food Microbiol. 2018, 2.

Saxelin M, Lassig A, Karjalainen H, Tynkkynen S, Surakka A, Vapaatalo H, Järvenpää S, Korpela R, Mutanen M, Hatakka K. Persistence of probiotic strains in the gastrointestinal tract when administered as capsules, yoghurt, or cheese. Int J Food Microbiol. 2010, 144(2): 293-300.

Szajewska H, Skórka A, Ruszczyński M, Gieruszczak-Białek D. Meta-analysis: Lactobacillus GG for treating acute gastroenteritis in children-updated analysis of randomised controlled trials. Aliment Pharmacol Ther. 2013 Sep;38(5):467-76.

Urbańska M, Gieruszczak-Białek D, Szajewska H. Systematic review with meta-analysis: Lactobacillus reuteri DSM 17938 for diarrhoeal diseases in children. Aliment Pharmacol Ther. 2016, 43(10):1025-34.

Vinderola G, Prosello W, Ghiberto D, Reinheimer J. Viability of  probiotic- (Bifidobacterium, Lactobacillus acidophilus and Lactobacillus casei) and non probiotic microflora in Argentinian Fresco Cheese (2000). J Dairy Sci. 2000, 83 (9), 1905-1911.

ISAPP recognizes Prof. Michael Cabana’s contributions during his board of directors tenure

/in featured, News /by Mary Ellen Sanders

Prof. Michael Cabana’s service on ISAPP’s board of directors has come to an end in 2018—and the remaining board members wish to affirm his rich legacy of contributions, which furthered ISAPP’s mission of advancing the science of probiotics and prebiotics.

Dr. Cabana, Professor of Pediatrics, Epidemiology and Biostatistics and the Director of the Division of General Pediatrics at the University of California, San Francisco (UCSF), joined the ISAPP board in 2008. He served as secretary for five years and treasurer for one year, and was local host for the 2011 ISAPP annual meeting in Berkeley, USA. He chaired discussion groups at eight different annual meetings:

  • 2009: Designing human clinical trials for probiotics
  • 2010: Prebiotics and probiotics in perinatal nutrition
  • 2012: From clinical trials to clinical guidelines:  Reconciling the evidence
  • 2013: Use of probiotics and/or prebiotics to program fetal and newborn health / first 1000 days of life
  • 2014: Infant colic:  Is there enough clinical evidence to support probiotic interventions?
  • 2015: Technology transfer and academic-industry partnerships
  • 2016: Colic update:  IPDMA and mechanisms
  • 2019: Prebiotic applications in children

 

Dr. Cabana was proactive in developing ISAPP responses to media misrepresentations of research by co-authoring letters to the editor in the New England Journal of Medicine (under review) and JAMA Internal Medicine (in press):

  • Guarner F, Cabana MD, Sanders ME. Late initiation of probiotic therapy for acute pediatric gastroenteritis may account for null results. New England J Med. Submitted.
  • Cabana MD, Salminen S, Sanders, ME. Probiotic safety – reasonable certainty of no harm. JAMA Internal Med. In Press.

As outcomes of ISAPP discussion groups or as part of other ISAPP initiatives, Dr. Cabana coauthored several papers, including:

 

Always a congenial and collaborative colleague, Dr. Cabana will be missed by the ISAPP board as he now turns his focus to other professional activities. Dr. Cabana’s UCSF lab has several ongoing trials related to the microbiome and probiotics in pediatric populations.

International Dairy Summit 2018 in Daejeon in South Korea

/in featured, ISAPP Science Blog /by Mary Ellen Sanders

By Prof. Seppo Salminen PhD, University of Turku, Finland

The International Dairy Federation (IDF) convenes annual meetings that bring together scientists and industry professionals to discuss issues foremost to the production of safe and nutritious dairy products globally. Since probiotics find a home in so many dairy foods worldwide, ISAPP and IDF have some overlapping interests.

ISAPP president, Prof. Seppo Salminen of University of Turku, spoke at IDF’s International Dairy Summit 2018 on the potential for fermented foods to fight diseases and improve nutrition. He emphasized that many fermented foods contain a diverse collection of live microorganisms, which likely support our gut microbiota, perhaps even promoting gut microbiota resilience. Further, he stated, “Fermented dairy products, especially yoghurt, which combines milk, microbial starter cultures and pre-digested nutrients for human use, can be considered for future food-based dietary guidelines or recommendations focusing on beneficial microbe intake for gastrointestinal and other health effects.”

Another speaker, Prof Bruno Pot, discussed the global situation with regard to health claims for fermented dairy products. He focused on the situation in the European Union, where the only allowed health claim for probiotics is the benefit from live bacteria (Lactobacillus bulgaricus and Streptococcus thermophilus) in yoghurt reducing symptoms of lactose maldigestion. He reported that yoghurt is becoming a mainstream food in Asia. Key growth drivers in Asia are the perceptions that yoghurt is a healthy product with its beneficial impact on the digestive and immune systems, and they offer a good source of protein and calcium. The symposium also explored ways to enrich food through product development and innovation, particularly to provide nourishment for vulnerable populations. The potential for new ingredients such as milk protein hydrolysate-calcium complexes as calcium sources in yoghurt production was recognized.

David Everett, Chair of IDF’s Standing Committee on Dairy Science and Technology, reported: “Holding the 6th edition of the Symposium on Fermented Milks in Asia is of tremendous value as the scientific research on fermented dairy and the interest in these products is growing in the region.”

Forthcoming changes in Lactobacillus taxonomy

/in featured, ISAPP Science Blog /by Mary Ellen Sanders

Mary Ellen Sanders PhD, Executive Science Officer, ISAPP

I was privileged to be included in a small meeting of scientists, both academic and industry, who met last week in Verona to discuss changes in Lactobacillus taxonomy. The first objectives of the meeting were to clarify with industry the need for the proposed changes and to clarify the methodology that will be used. The second objectives were to discuss at large potential consequences and approaches to address them.

Changes to the Lactobacillus genus

Experts from the Taxonomic Subcommittee for Lactobacilli, Bifidobacteria and Related Organisms agreed that the genus Lactobacillus is too heterogeneous and dividing this genus into several genera is inevitable. The need for this taxonomic ‘correction’ has been known for a long time, but until recently, the methodologies needed to reliably group the current Lactobacillus species into new genera were not available. But earlier this year, a paper by Salvetti et al (2018) analyzed 269 Lactobacillus and related (e.g., Pediococcus, Leuconostoc, Fructobacillus, Oenococcus) species and showed that the Lactobacillus genus comprises 10 phylogroups (see box). Each of these phylogroups represents at least one new genus. These same 10 phylogroups were observed using three separate approaches [phylogenetic analysis of 16S ribosomal DNA sequences, whole genome sequence analysis, leading to the comparison of 72 shared housekeeping genes (the core genome), and the comparison of average amino acid identity and percentage of conserved proteins], providing strong evidence that these groupings are robust. Commercially important Lactobacillus probiotic strains span at least 7 of those newly defined phylogroups; food fermentation lactobacilli cover even more.

lactobacillus_info

Although these 10 phylogroups were identified by this study, the current genus Lactobacillus could ultimately be resolved into 10 or up to 23 genera, depending on the cut-off values used for the different approaches. If researchers choose to split the genus into fewer new genera, it increases the chance that taxonomic changes will be needed in the nearer future. If they split the genus into more genera, it increases the chance that nomenclature will remain stable.

The names of the new genera are not decided. New names must be published (or validated) in the International Journal of Systematic and Evolutionary Microbiology. The authors of the publication will propose the new genus names. All species will be retained and their species names will not change. To minimize disruption, researchers will try to propose new genera names that begin with the letter “L”. Because “Lactobacillus” is a masculine Latin noun, the new genus names must be masculine for the species names to be retained.

A silver lining

Critics of these changes may suppose that adhering to taxonomic convention is their only purpose. But a classification system that better reflects genetic relatedness of the species may reap other benefits. As evidence for clinical benefits accumulates (summarized in open access review “Probiotics for Human Use”, 2018) and investigations provide insight into probiotic mechanisms of action, a clearer image of mechanisms and functions associated with particular taxonomic groups may emerge. The concept of core, shared benefits that were not strain-specific but linked to higher taxonomic groupings was explored in two ISAPP publications [Hill et al. (2014) and more in depth in Sanders et al. (2018)]. Reconsideration of clinical evidence and its relationship to new genera might prove enlightening.

What can be done to minimize confusion?

The meeting attendees brainstormed potential complications that might result from changing genus names. Company representatives in general considered that internal changes could be managed, although resources would be required to update names on all different paperwork and labels associated with commercial products (for example, marketing materials, product information, certificates of analysis, labeling, import/export certificates). The 2002 WHO/FAO probiotic guidelines, as well as the 2017 CRN/IPA guidelines, indicate that the genus, species and strain designation should be included on product labels. Further, the name used should reflect current nomenclature. This requirement is reflected in some national regulations. Therefore, genus name changes will necessitate label changes.

Further, it was emphasized that a clear document should be prepared and endorsed by reputable organizations (EFSA, NIH, FDA, medical organizations, and others). The document should: (a) indicate the name changes, (b) provide a clear, concise statement of why the changes were needed, and (c) emphasize that only the names, not the strains, would be different. This could be leveraged by companies to communicate with all stakeholders. End-users of probiotic products would likely not be a significant communication challenge. Authorities involved with probiotic safety (FDA with GRAS and EFSA with QPS) likely will manage these changes, as they are science-based. More of a concern was communication with other regulators, both at the level of national agencies responsible for probiotic-specific regulations (including countries with positive lists of species that are acceptable as probiotics) as well as authorities involved in import/export of product. Some potential issue with intellectual property may be envisaged, especially in a transition period during which the new names are not routinely used yet.

The bottom line: Name will change but the strains will stay the same 

The current Lactobacillus genus will be split into at least 10, and perhaps as many as 23, genera. No species names will change, but many species – including commercially important ones – will have a different genus names, hopefully beginning with the letter “L”.  Because of the tremendous heterogeneity of the current Lactobacillus genus, Prof. Paul O’Toole concluded his presentation saying “the status quo is not an option.” Some disruptions can be expected from this massive change, but the probiotic field would benefit from embracing these changes and developing strategies to minimize any difficulties resulting from them.

 

Additional information:

The International Committee on Systematics of Prokaryotes (ICSP) and the International Code of Nomenclature of Bacteria are responsible for the naming of bacteria. The subcommittee of the ICSP responsible for naming lactobacilli is the Taxonomic Subcommittee for Lactobacilli, Bifidobacteria and Related Organisms.

The meeting was convened by the Lactic Acid Bacteria Industrial Platform and chaired by Esben Laulund of Chr Hansens, who also chairs IPA Europe. A full report of meeting conclusions is expected to be published in a scientific journal by the end of 2018. Abstracts and program will to be posted on the LABIP website in due time.

The taxonomic hierarchy for Lactobacillus currently is: Domain: Bacteria; Division/Phylum: Firmicutes; Class: Bacilli; Order Lactobacillales; Family: Lactobacillaceae; Genus: Lactobacillus. The lowest order of taxonomy is the subspecies; the strain designation has no official standing in nomenclature. There are currently over 230 recognized species of Lactobacillus, and approximately 10 new species are added each year.

‘Brain fogginess’ and D-lactic acidosis: probiotics are not the cause

/in featured, News /by Mary Ellen Sanders

Mary Ellen Sanders PhD, Executive Science Officer, International Scientific Association for Probiotics and Prebiotics

Bruno Pot PhD, Research Group of Industrial Microbiology and Food Biotechnology, Faculty of Sciences and Bioengineering Sciences, Vrije Universiteit Brussel, Pleinlaan 2, B-1050 Brussels, Belgium

See here for ISAPP letter to the Clinical and Translational Gastroenterology editor regarding this paper.

See related post Probiotics and D-Lactic Acid Acidosis in Children

Rao and colleagues incriminated probiotics in the induction of D-lactic acidosis in their paper titled “Brain fogginess, gas and bloating: a link between small intestinal bacterial overgrowth (SIBO), probiotics and metabolic acidosis” (Rao et al. 2018). Eamonn Quigley MD, Bruno Pot, microbiologist and I on behalf of ISAPP authored a letter to the editor of Clinical and Translational Gastroenterology (currently In Press), summarizing many medical and other concerns with the study design, execution and conclusions.

It is regrettable that one poorly controlled paper can lead to such negative backlash on the probiotic field. Respectable media outlets including Newsweek, Science Daily, Psychology Today, the Daily Mail, MSN.com, and others blindly reported the results of this study without critical analysis of the paper. These stories advance the opinion that probiotics are potentially harmful and should be sold only as drugs. This flies in the face of many scientific studies that document safety compounded with safe, worldwide consumption for decades of probiotic foods and supplements.

Bifidobacterium as a genus does not yield D-lactate as a metabolic end product. Some Lactobacillus species do (Table 19.1 in Pot 2014). Among common probiotic Lactobacillus species, the following are classified as species that can produce D-lactic acid: L. acidophilus, L. gasseri, L. delbrueckii subsp. bulgaricus (one of the 2 yogurt starter culture bacteria), L. fermentum, L. lactis, L. brevis, L. helveticus, L. plantarum and L. reuteri.  Individual strains within each species may vary with regard to levels of D-lactic acid produced.

The observational nature of the Rao et al. paper precludes any conclusive link between probiotic consumption and symptoms observed.  The authors acknowledge that they have only established an association between probiotic use and the symptoms, but the misleading paper title suggests an intention to indict probiotics, even in the absence of evidence.  It is much more likely that the patient population with underlying SIBO in this study sought relief from their gut symptoms by use of probiotics rather than the probiotics being the cause of their symptoms.

D-lactic acidosis is a rare but serious condition, typically occurring in people with short bowel syndrome. These patients should know that D-lactate-producing probiotics are not recommended for them. In people with a normal gut, D-lactate produced by members of the gut microbiota – including some probiotics – is metabolized by other members of the gut microbiota and does not accumulate. Thus, under normal circumstances, D-lactic acidosis does not result from consumption of D-lactic acid-producing probiotics. The patients in the Rao et al. study showed very low levels of D-lactic acid, calling into question if these SIBO patients were even acidotic.  Moreover, the D-lactic acid that was present was not proven to be a result of probiotic growth. This is important, as intestinal bacteria including Escherichia coli also produce D-lactic acid. In cases of SIBO, numerous metabolites are produced in the small intestine (including alcohol), leading to a variety of SIBO symptoms, possibly including the poorly defined phenomenon of “brain fogginess”.  Many issues that should have been were not addressed in the Rao et al. paper.

The real tragedy with the publication of this paper is that – similar to many such media scares in the past – it is may cause harm.  The sensationalist headlines may dissuade safe probiotic use in people who can truly benefit from them. Scientists and clinical researchers – both academic and from industry – must remain diligent in assessment and reporting of any probiotic harms. However, the Rao et al. paper is not an example of this.

Reference:

Pot B. 2014. The genus Lactobacillus. Chapter 19. In Lactic Acid Bacteria: Biodiversity and Taxonomy, First Edition. Edited by Wilhelm H. Holzapfel and Brian J.B. Wood. 2014 John Wiley & Sons, Ltd.

Other reading:

Mack D. 2004. D(-)-lactic acid producing probiotics, d(-)-lactic acidosis and infants. Canadian J Gastroenterol. 18:671-5. (ISAPP-commissioned paper)

Łukasik J, Salminen S, Szajewska H. Rapid review shows that probiotics and fermented infant formulas do not cause d-lactic acidosis in  healthy children. Acta Paediatr. 2018 Aug;107(8):1322-1326. doi: 10.1111/apa.14338. Epub 2018 Apr 24.

definition

ISAPP conducts webinar on definitions in microbiome space for ILSI-North America Gut Microbiome Committee

/in featured, News /by Mary Ellen Sanders

Dr. Mary Ellen Sanders presented a webinar July 23, 2018 – covering basic definitions of microbiota-mediated terminology – to the ILSI-North America Gut Microbiome Committee, which you can listen to here. The objective was to update the committee about terms with clear and actionable consensus definitions in the microbiome space. ISAPP is committed to proper use of terms such as ‘probiotics’ and ‘prebiotics’, as evidenced by the consensus panels it has convened (see here and here) on these topics. Definitions of some newly emerging terms such as postbiotic, abiotic, and probioceuticals are less clear.

Some issues covered in this webinar include comparison with historic definitions, minimum criteria for commercial probiotic and prebiotic products, contrasting probiotic food with fermented food, and a brief discussion of imminent taxonomy changes for the genus, Lactobacillus.

The webinar is now available here.