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pigs in mud

The gut-brain axis in livestock animals: Is there a place for biotics in changing pig behavior?

/in ISAPP Science Blog /by KC

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

When pigs are kept as livestock, ‘manipulative behaviour’ is relatively common and it most often consists of biting, touching, or close contact with ears or tails of pen mates, without always resulting in visible wounds. Such pig behavior can cause stress and sometimes results in physical injuries. Chronic stress, nutritional deprivation, diet formulation, health problems, environmental discomfort, high stocking density and competition over resources are among the reported risk factors for tail biting in pigs. However, the precise factors behind behavioral problems in domesticated pigs remain poorly understood. It has been suggested that manipulative behavior may be associated with gut microbiota composition and activity via the gut-brain axis, with potential influence from the metabolites produced by gut microbes.

A multidisciplinary team of researchers recently assessed manipulative pig behaviour and gut microbiota interrelations (König et al. 2024). The aim was to identify pigs performing tail and/or ear manipulation (manipulator pigs) and to compare their fecal microbiota with that of control pigs not manifesting such behaviour. The study was conducted by analyzing video recordings of 45-day-old pigs. Altogether 15 manipulator-control pairs were identified (n = 30). Controls did not receive nor perform manipulative behaviour.

Rectal fecal samples of manipulators and controls were compared on two parameters: (1) culturable lactobacilli, and (2) microbiota composition. 16S PCR was used to identify Lactobacillaceae species after culture isolation, and 16S amplicon sequencing was used to determine fecal microbiota composition. The researchers found fewer culturable Lactobacillaceae species in fecal samples of pigs performing manipulative behaviour, with seven culturable Lactobacillaceae species identified in control pigs and four in manipulator pigs. Manipulators (p = 0.02) and female pigs (p = 0.005), however, expressed higher overall counts of Lactobacillus amylovorus, and the researchers found a significant interaction (sex * status: p = 0.005) with this sex difference being more marked in controls. Manipulator pigs tended to express higher total abundance of Lactobacillaceae but lower alpha diversity. A tendency for an interaction was seen in Limosilactobacillus reuteri (sex * status: p = 0.09). The results add to the findings of an earlier study reporting that intestinal microbiota was changed and lactobacilli were more abundant in a negative control group compared with biting pigs (Rabhi et al. 2020). Taken together, these studies suggest that specific lactobacilli  as well as low diversity of Lactobacillaceae may be factors impacting manipulative behavior.

Manipulative behavior is an important challenge in swine production as it impacts animal welfare and health and the economics and safety of the pork meat supply chain. With emerging information on the gut-brain axis in various animals, scientists are exploring the potential contributions of intestinal microbiota to such behaviors. With recent studies suggesting that there may be a link between observed low diversity in species of Lactobacillaceae and the development of manipulative behaviour, perhaps specific biotics could be used to increase and modulate lactobacilli (selected species and diversity) to control tail and ear biting in pigs. Studies in the future may investigate this possibility.

References

König E, Heponiemi P, Kivinen S et al. Fewer culturable Lactobacillaceae species identified in faecal samples of pigs performing manipulative behaviour. Sci Rep. 2024;14:132. doi: 10.1038/s41598-023-50791-0.

Rabhi N, Thibodeau A, Côté JC, Devillers N, Laplante B, Fravalo P, Larivière-Gauthier G, Thériault WP, Faucitano L, Beauchamp G, Quessy S. Association Between Tail-Biting and Intestinal Microbiota Composition in Pigs. Front Vet Sci. 2020 Dec 9;7:563762. doi: 10.3389/fvets.2020.563762.

Episode 28: Lactobacilli in the microbiomes of the gut, skin, reproductive tract and more

/in Podcast, Season Two /by Laura

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The Science, Microbes & Health Podcast 

This podcast covers emerging topics and challenges in the science of probiotics, prebiotics, synbiotics, postbiotics and fermented foods. This is the podcast of The International Scientific Association for Probiotics and Prebiotics (ISAPP), a nonprofit scientific organization dedicated to advancing the science of these fields.

Lactobacilli in the microbiomes of the gut, skin, reproductive tract and more, with Prof. Kingsley Anukam PhD

Episode summary:

In this episode, the ISAPP podcast hosts cover a range of topics related to lactobacilli and health with Prof. Kingsley Anukam PhD from Nnamdi Azikiwe University in Nigeria. Prof. Anukam has a special interest in lactobacilli, and studies lactobacilli in microbiomes across many different contexts: fermented foods, skin, gut, and reproductive tract sites. He talks about the wide range of research he has led in Nigeria using diverse sources of funding.

Key topics from this episode:

  • Prof. Anukam describes his collaboration with Prof. Gregor Reid PhD early in his career, prompted by a paper claiming that African women did not have vaginal microbiomes dominated by lactobacilli. Subsequent work showed this was not the case – confounding factors contributed to the initial result.
  • He cautions researchers against making conclusions about race or ethnicity when geographical variations or other factors could better account for the differences between groups. In studies it’s important to specify the geography as well as the other factors (dietary, cultural) that may impact the gut microbiome in these populations.
  • There is a long history of fermented foods in Africa but not a lot of research has been done on them. In a 2009 paper with Prof. Reid, Prof. Anukam reported isolated lactic acid species from a fermented food called okpeye produced in Eastern Nigeria. The isolates showed potential for industrial applications.
  • Most of his research studies are funded from outside Nigeria, with different sources of funding.
  • ‘Parachute’ science is common in Africa, where researchers come into an African country, obtain samples and leave. He encourages researchers to involve local scientists to build capacity and allow them to do the analysis.
  • Prof. Anukam describes a clinical trial he led on the skin microbiome and malodor in Nigerian youth. He found the skin microbiome in the armpit was altered if individuals used deodorants and antiperspirants; and these individuals kept having the same malodor issues. Individuals with less odor were found to have more lactobacilli on the skin, with differences in composition between men and women. They developed a topical cream to use as an intervention for 14 days, and found that lactobacilli on the skin increased and less odor was reported.
  • The microbiome(s) of the male reproductive organs have not been studied very much. Semen has a microbiome, and this is shown by both culture and non-culture methods. It is dominated by lactobacilli, and this corresponds with semen quality. The evidence is mixed on the existence of testes and prostate microbiomes. A gut-testes connection may exist, however, as shown in mouse studies.
  • Prof. Anukam says in a study of subjects seeking reproductive healthcare, different microbiomes were observed both in males and females having difficulty conceiving.
  • The semen microbiome could play a significant role in reproduction – for example, it may produce metabolites that could affect the female reproductive tract and influence the environment for conception to take place. When doing in vitro fertilization, evidence has shown that if the samples are contaminated by pathogens, it can be difficult to achieve conception.

Episode links:

About Prof. Kingsley Anukam PhD:

Kingsley C Anukam is a research scientist in human microbiome and biotherapeutics with over 20 years experience. He shares his time between Canada and Nigeria as an adjunct professor at Nnamdi Azikiwe University where he assists in the training and supervision of post graduate students working in the area of probiotics, fermented foods, human microbiome, infectious diseases, laboratory diagnostics, human genomics and forensic DNA analysis. He had his graduate education in Nigeria and post doctorate training in Dr. Gregor Reid’s Lab at Lawson Health Research Institute and Department of Microbiology and Immunology, Western University, Canada. He is the first from Africa to show that vaginal microbiome of healthy Nigerian women is similar to women from other populations irrespective of geographical location. He has sequenced and annotated the full genome of over 10 Lactobacillus species of African origin mainly from the reproductive tract and African fermented foods in collaboration with Prof. Sarah Lebeer. He played a significant role in the formation of the DORA project, an ISALA-inspired citizen science for vaginal health in Nigeria. He has over 80 scientific research publications in peer-reviewed journals and listed among first 10 most cited researcher at Nnamdi Azikiwe University by Google Scholar. He is currently the Chief Editor, Journal of Medical Laboratory Science, and a peer-reviewer of several international journals.

Bacterial genes lead researchers to discover a new way that lactic acid bacteria can make energy and thrive in their environments

/in ISAPP Science Blog /by KC

Lactic acid bacteria are an important group of bacteria associated with the human microbiome. Notably, they are also responsible for creating fermented foods such as sauerkraut, yogurt, and kefir. In the past two decades, culture-independent techniques have allowed scientists to sequence the genomes of these bacteria and discover more about their capabilities.

Researchers studying a type of lactic acid bacteria called Lactiplantibacillus plantarum found something unexpected: they contained genes for making energy in a way that had not been previously documented. Generally, living organisms obtain energy from their surroundings either by fermentation or respiration. L. plantarum have long been understood to obtain energy using fermentation, but the new genetic analysis found they had additional genes that were suited to respiration. Could they be using both fermentation and respiration?

ISAPP board member Prof. Maria Marco is a leading expert on lactic acid bacteria and their role in fermented foods and in human health. In her lab at University of California Davis, she decided to investigate why L. plantarum had genes equipping it for respiration. Her group recently published findings that show a new type of “hybrid” metabolism used by these lactobacilli.

Here is a Q&A with Prof. Marco about these exciting new findings.

What indicated to you that some of the genes in L. plantarum didn’t ‘belong’?

Organisms that use respiration normally require an external molecule that can accept electrons, such as oxygen. Interestingly, some microorganisms can also use solid electron acceptors located outside the cell, such as iron. This ability, called extracellular electron transfer, has been linked to proteins encoded by specific genes. L. plantarum had these genes, even though this species is known to use fermentation. We first learned about their potential function from Dr. Sam Light, now at the University of Chicago. Sam discovered a related pathway in the foodborne pathogen Listeria monocytogenes. Sam came across our research on L. plantarum because we previously published a paper showing that a couple of genes in this pathway are switched on in the mammalian digestive tract. We wondered what the proteins encoded by these genes were doing.

How did you set out to investigate the metabolism of these bacteria?

We investigated this hybrid metabolism in a variety of ways. Using genetic and biochemical approaches we studied the extent to which L. plantarum and other lactic acid bacteria are able to use terminal electron acceptors like iron. Our collaborators at Lawrence Berkeley National Lab and Rice University contributed vital expertise with their electrochemistry experiments, including making fermented kale juice in a bioelectrochemical reactor.

What did you find out?

We discovered a previously unknown method of energy metabolism in Lactiplantibacillus plantarum. This hybrid strategy blends features of respiration (a high NAD+/NADH ratio and use of a respiratory protein) with features of fermentation (use of endogenous electron acceptors and substrate-level phosphorylation).

We verified that this hybrid metabolism happens in different laboratory media and in kale juice fermentations. We also found that, in the complex nutritive environment of a kale juice fermentation, this hybrid metabolism increases the rate and extent of fermentation and increases acidification. Within the ecological context of the fermented food, this could give L. plantarum a fitness advantage in outcompeting other microorganisms. This could potentially be used to change the flavor and texture of fermented foods.

This discovery gives us a new understanding of the physiology and ecology of lactic acid bacteria.

Are there any indications about whether this energy-making strategy is shared by other lactic acid bacteria?

Some other fermentative lactic acid bacteria also contain the same genetic pathway. It is likely that we are just at the tip of the iceberg learning about the extent of this hybrid metabolism in lactobacilli and related bacteria.

Your finding means there is electron transfer during lactic acid bacteria metabolism. What does this add to previous knowledge about bacterially-produced ‘electricity’?

Certain soil and aquatic microbes have been the focus of research on bacterially-produced electricity. We found that by giving L. plantarum the right nutritive environment, it can produce current to the same level as some of those microbes. We believe there is potential to apply the findings from our studies to better inform food fermentation processes and to guide fermentations to generate new or improved products. Because strains of L. plantarum and related bacteria are also used as probiotics, this information may also be useful for understanding their molecular mechanisms of action in the human digestive tract.

How might this knowledge be applied in practice?

Our findings can lead to new technologies which use lactic acid bacteria to produce healthier and tastier fermented foods and beverages. Because this hybrid metabolism leads to efficient fermentation and a larger yield, it could also help minimize food waste. We plan to continue studying the diversity, expression, and regulation of this hybrid metabolism in the environments in which these bacteria are found.

Lactobacilli dominate the vagina in Belgian women

/in ISAPP Science Blog /by KC

By Prof. Sarah Lebeer, Research Professor in Microbiology and Molecular Biology, Department of Bioscience Engineering, University of Antwerp, Belgium

A little over a year ago, I wrote an ISAPP blog post about the setup of our Isala citizen science project on women’s health. Now, I can proudly say that we have the first results. Last year, more than 3300 women sent vaginal samples back to our lab, not only from the big cities but also from the smallest villages all over Flanders, Belgium (Figure 1). While Prof. Jack Ravel and many other colleagues have already done pioneering work in the US (e.g., Ravel et al. PNAS & Valencia study), Estonia and Africa, the vaginal microbiome of healthy women was less well mapped in the region where we live in Western Europe (Flanders, Belgium).

Figure 1: Map of Flanders (Belgium) showing regions from which the Isala participants sent their samples, with a gradient for the number of participants.

Last year, we managed to inspire women from a wide age range to donate two vaginal self-sampled swabs: the youngest participants were 18 years old, while a woman of 98 years old even participated. Each participant of Isala showed a unique vaginal microbiome (Figure 2).

Figure 2. Bar chart showing that each Isala participant had a unique vaginal microbiome composition, but also that lots of parallels could be drawn based on the most dominant bacterium.

Through various analyses, we were able to find parallels between the vaginal profiles of the Isala participants. We decided to divide the women in eight groups based on their most dominant microbe. Lactobacillus crispatus was found in 43% of all Isala women as most dominant bacterium, Lactobacillus iners in 28%, Lactobacillus jensenii in 4%, Lactobacillus gasseri in 3%, Gardnerella vaginalis in 12%, Prevotella in 6%, Bifidobacterium in 2% and Streptococcus in 2% of all Isala participants (Figure 3). Last June 2021, all women received this information, with a nice drawing for each bacterium and some interesting facts about these bacteria, as well as the relative abundance of this top 8. (See here.)

Figure 3. Chart showing the proportion of women participating in the Isala project that have a vaginal microbiota dominated by different bacterial genera or species.

Our work has only just begun. My team (see photo below) is now analyzing all the metadata collected via the detailed questionnaires and associating them with these microbiome profiles. The impact of the menstrual cycle, hormonal fluctuations, diet, smoking, sexual activity and other relevant factors is currently being explored. Hopefully, this will allow us to better understand for the vaginal tract what a ‘healthy microbiome’ really is and what action women can take to obtain or preserve  a ‘healthy’ or resilient microbiome. This is challenging to define with our current state of knowledge, but one characteristic of health of the microbiome may be its resilience. At the next annual ISAPP meeting, Karen Scott and I will co-chair a discussion group on ‘What do we really know about the microbiome and health?’. Now, I think it is fair to say that, compared to the gut, associations between specific microbiome members, such as lactobacilli, and health are quite strong for the vaginal tract. These lactobacilli form a protective barrier, are able to keep pathogens out, and prevent overt inflammation, so we could define lactobacilli-dominated vaginal communities as being resilient to many infections and disorders and thus probably ‘healthy’.

However, there is still much we do not know. Can women make certain changes in their lifestyle, diet, anticonception, underwear material etc. to promote lactobacilli such as L. crispatus in their vagina? What are the consequences of normal events in live such as pregnancy and menopause on these lactobacilli? Is a vaginal community with less lactobacilli always less healthy or resilient? On this page, you can get an overview of the different aspects we want to investigate. We hope to submit the first big Isala manuscript by the end of this year and will inform you as soon as possible about the results.

Lebeer lab, University of Antwerp

Can control of body malodor using probiotic topical cream be considered as a health benefit?

/in ISAPP Science Blog /by KC

By Victoria Onwuliri, Masters degree student, with Dr. Kingsley C. Anukam, Department of Medical Laboratory Science, Faculty of Health Sciences and Technology, College of Health Sciences, Nnamdi Azikiwe University, Nnewi Campus, Nnewi, Anambra State, Nigeria.

I recall years back as a teenager, axillary sweating and pubertal odor were one of the overwhelming challenges I experienced. It really affected how I related with the people around me, and I became socially withdrawn. I was introduced to the use of deodorants after a very attractive advertisement on television. Truthfully, though, these personal hygiene products were not a good match for my active teenage lifestyle because their effects waned easily and I was back to my sweaty self. This continued with all different products I used; they would wear off, leaving my axilla smelling stronger than before. Sharing my experience with other adolescents like me made me realize that we all were facing similar issues and were seeking a long-lasting solution. I am very certain many teenagers and young adults all over the world are currently experiencing same problem and are in need of a solution.

Later on, as a scientist, I wondered if I could explore a solution for this problem. First, what was causing the odor? Several fundamental studies have shown that the apocrine gland that is located in the hypodermis of the skin is responsible for secreting the odorless precursor molecules. These precursors are transformed by some bacteria residing on the skin into smelly molecules including but not limited to sulphanylalkanols, short volatile branched-chain fatty acids and some steroid derivatives. It should be noted that both males and females produce some levels of body odor, but the intensity varies as females have 75% more apocrine glands in their armpits than males but males have larger apocrine glands. The differences in the size and number of apocrine glands may explain why males tend to smell more than females. (I hope my male colleagues will not take offense for my sharing this fact). However, differences in hygiene habits such as regular shaving, use of antiseptic soap, use of deodorants and antiperspirants could also play a role.

I was involved in a study with Dr. Kingsley C. Anukam as my supervisor in 2019 on the effect of antiperspirants and deodorants on the axillary skin microbiome of adult male and female subjects. This study supported my teenage observation that I was worse off after using these products: the study showed that the resultant effect of the regular use of these personal hygiene products was an imbalance in the seemingly normal bacterial population of the axillary skin, thereby promoting the proliferation of malodor-producing organisms such as Corynebacterium, Cutibacterium, some Staphylococcus and Streptococcus species. Interestingly lactobacilli were also detected in the axilla of over 82% of female and over 81% of male subjects, though in low relative abundance which suggests that lactobacilli might be considered as part of the normal axillary bacterial community. From this work, an idea emerged on exploring the possible beneficial effect of probiotics in decreasing the relative abundance of malodor-producing bacteria in the axilla of healthy adult individuals.

Dr. Anukam and I set up a study and employed the use of oil-based topical cream, made from natural ingredients, fortified with a probiotic of Nigerian origin, Lactiplantibacillus pentosus KCA1 strain.

Since some species of Corynebacterium (particularly Corynebacterium striatum, and Corynebacterium jeikeium), and Staphylococcus haemolyticus, Staphylococcus hominis, and Staphylococcus lugdunensis isolated from human axilla have been implicated in the generation of malodour volatile substances 1,2, and the fact that we identified lactobacilli in low abundance in the axilla of healthy subjects compared with Corynebacterium and Staphylococcus species, Dr. Anukam, agreed that applying lactobacilli, (which are generally regarded as safe bacteria) to the skin might change the ecology to a state whereby some lactobacilli with probiotic characteristics can nestle on the axillary skin.

The data obtained from the study3 which has already been published in the Journal of Cosmetic Dermatology (https://doi.10.1111/jocd.13949) showed the positive impact of this probiotic-fortified topical cream on the human axillary skin microbiota, as a means of reducing axillary malodor. We drew this conclusion based on the fact that malodor-producing Staphylococcus and Corynebacterium species were significantly reduced in abundance after applying the probiotic cream. In addition, all the participants gave positive feedback as they reported not perceiving any malodor during the study period.  Another interesting in silico finding from the study was the down-regulation of the bacterial metabolic functional genes such as the PLP-dependent protein (K06997) and pyridoxal 5′-phosphate synthase pdxS subunit (K06215) after the application of the probiotic cream.

This appears much more desirable when compared to the effect of regular usage of antiperspirants and deodorants on the axillary skin microbiome.

However, some arguments have arisen whether reduction of body odor could be taken as a health benefit since probiotic definition stipulates that a probiotic must ‘confer a health benefit on the host’. We know that body malodor has some social and psychological implications to some people which might impact negatively on their mental health. We therefore suggest that using tested microorganisms to reduce body malodor may contribute to the wellbeing of individuals, so this would count as a probiotic intervention.

We are not saying that probiotic cream alone would completely solve the problem of axillary skin/body malodor, but we believe its positive effect outweighs that of the antiperspirants and deodorants. In addition, the potential beneficial effects of skin-based probiotics could be increasingly explored by the cosmetic and pharmaceutical industries. Regarding our work, further study involving a larger population and more insight on the functional malodor control attributes of lactobacilli are warranted. I know teenagers everywhere are waiting for this breakthrough.

Preparation of topical cream fortified with Lactiplantibacillus pentosus KCA1

(GeneBank Accession # NZ_CM001538.1)

The study used natural ingredients that have already-known benefits on the skin, in the preparation of the topical cream. During the preparation, ingredients were heated and purified, in order to maintain sterility and keep them in their oil forms before the incorporation of the lyophilized Lactiplantibacillus pentosus KCA1.

Finished product:

 

 

Ingredients:

Cocoa butter, coconut oil, lavender oil, shea butter, lyophilized Lactiplantibacillus pentosus KCA1

 

 

References

  1. Natsch A, Schmid J, Flachsmann F. Identification of odoriferous sulfanylalkanols in human axilla secretions and their formation through cleavage of cysteine precursors by a C-S lyase isolated from axilla bacteria. Chem Biodivers. 2004;1(7):1058–72
  2. Bawdon D, Cox DS, Ashford D, James AG, Thomas GH. Identification of axillary Staphylococcus sp. involved in the production of the malodorous thioalcohol 3-methyl-3-sufanylhexan-1-ol. FEMS Microbiology Letters 2015; 362: fnv111. doi: 10.1093/femsle/fnv111
  3. Onwuliri V, Agbakoba NR, Anukam KC. Topical cream containing live lactobacilli decreases malodor-producing bacteria and downregulates genes encoding PLP-dependent enzymes on the axillary skin microbiome of healthy adult Nigerians. J Cosmet Dermatol. 2021;00:1–10. https://doi.org/10.1111/jocd.13949

 

 

 

Victoria Onwuliri is a Master degree student in the Department of Medical Laboratory Science, Faculty of Health Sciences and Technology, College of Health Sciences, Nnamdi Azikiwe University, Nnewi Campus, Nnewi, Anambra State, Nigeria.

In Memoriam: Todd Klaenhammer

/in ISAPP Science Blog, News /by KC

By Mary Ellen Sanders and Colin Hill

We all suffered a devastating loss this past Saturday with the death of Prof. Todd Klaenhammer, aged 69.

Todd was a larger-than-life figure in the scientific field of genetics of lactic acid bacteria. Todd’s 38-year career started at the age of 26, when he joined North Carolina State University as an assistant professor in 1978. His research and teaching awards are too numerous to count, as the phrase goes, but of special note was his election in 2001 to the U.S. National Academy of Sciences. Later he also received the O. Max Gardner award, given to one researcher in the North Carolina University system “who has made the greatest contribution to the welfare of the human race.”

Gregor Reid, Todd Klaenhammer, Colin Hill and Paul Ross in Tromso, Norway.

For those of us fortunate enough to work closely with him, it was a privilege to witness his mind at work, making those leaps in understanding in real time as he furiously forged ahead of the data while designing strategies to test his theories. He saw the potential for probiotics when few others were interested. He led the field in phage resistance, in bacteriocin research, and in basic lactic acid bacterial genetics. When many preferred to study the more genetically accessible lactococci he went with the much more recalcitrant lactobacilli. The discoveries he made were all the more notable because he always maintained a relatively small laboratory group, not moving to the large team-based approaches that are more common today. He was a fierce competitor, but was warm and generous when his friends and rivals made scientific advances. His willingness to take on challenges was truly inspirational, and his scientific intellect was the rock-solid foundation for everything he achieved in a legendary career.

As a founding board member for ISAPP, serving on the board from 2002 to 2016, Todd helped shape ISAPP’s development. He had a great influence on ISAPP leadership, nudging Prof. Colin Hill to serve as president and nominating Prof. Sarah Lebeer to the board. He, along with Prof. Jeff Gordon, organized the National Academy of Sciences Sackler Symposium “Microbes & Health” in conjunction with the 2009 ISAPP annual meeting at the Beckman Center in Irvine CA. Later, one of ISAPP’s finest moments was the gala dinner during the 2015 ISAPP meeting in Washington DC, which Todd hosted at the National Academy of Sciences Great Hall.

Colin Hill, Todd Klaenhammer, Dymphna Hill and Mary Ellen Sanders at dinner after the 2012 ISAPP annual meeting in Cork, Ireland.

Todd seemed especially happy when he was able to help young scientists succeed in science. His “work hard, play hard” ethic and his fierce dedication made positions in his lab coveted. Competition for a space in his lab became steeper as the years went by. The best and the brightest students and postdocs found their way to his lab over the years, and he was extremely proud of all that those in his lab accomplished.

Todd always welcomed the opportunity to connect with his many colleagues and friends. He was rarely without a story to share – watching his Ford Bronco start to sink into the lake with his cherished golden retriever paddling in the back was a favorite. The listening throng always radiated congeniality. He could work a crowd.

Saying goodbye to Todd will be hard for so many of us across the globe. We will miss his good humor, his friendship, his constant encouragement of others to excel, and his hustle to make sure they did.

Rest in peace, Todd. We will try to continue to make you proud.

Mary Ellen Sanders was a graduate student in the Klaenhnammer lab from 1978-1983. Colin Hill was a postdoc in the Klaenhammer lab from 1988-1990.

Todd Klaenhammer (second from left) with other participants in the 2010 ISAPP meeting in Barcelona.

Read more about Todd Klaenhammer’s life and career:

The Passing of Todd Klaenhammer. Annual Review of Food Science and Technology

Beloved Dairy Researcher Klaenhammer Dies

OBITUARY. Todd Robert Klaenhammer

Biography of Todd R. Klaenhammer

A Lasting Legacy: Probiotics Pioneer Todd Klaenhammer Retires

New endowments created honoring Klaenhammer’s legacy in probiotics research

From the Japan Society of Lactic Acid Bacteria: Memory of Prof. Todd R. Klaenhammer (Prof. Todd R. Klaenhammerを偲ぶ), Dr. Mariko Shimizu-Kadota and A legend of LAB is gone (Todd R. Klaenhammer先生を偲んで), Dr. Akinobu Kajikawa. Japan Society of Lactic Acid Bacteria Journal.

Citizen scientists step up for a research project on women’s health

/in ISAPP Science Blog /by KC

By Prof. Sarah Lebeer, Research Professor in Microbiology and Molecular Biology, Department of Bioscience Engineering, University of Antwerp, Belgium

Lactobacilli are a very important group of bacteria that live on the human body and in many other environments on Earth. They have been linked to human health for more than 100 years already, but mainly in the context of digestive health and dairy-based fermented foods. Knowledge about other habitats and applications of lactobacilli is lagging behind, and surprisingly, we know little about where lactobacilli come from in the life of an individual or even in the evolution of humans. Studying the genetic capabilities of lactobacilli and their interactions with the host will give us a clearer picture of how these bacteria help us stay healthy.

This knowledge gap inspired me to apply for a European Research Council (ERC) grant. Last year I was awarded with this prestigious grant, which provides funding to explore novel aspects about the ecology and evolutionary history of lactobacilli.

Lactobacilli are dominant colonizers of the human vagina, where they play a key role in women’s health. Among the lactobacilli, I consider the vaginal lactobacilli as ‘mother lactobacilli’. As you might have noticed from our recent reclassification of the Lactobacillus genus complex, the vaginal type strains Lactobacillus crispatus, Lactobacillus gasseri, Lactobacillus jensenii and Lactobacillus iners all belong to the Lactobacillus genus strictu sensu, because they are closely related to the first Lactobacillus species ever described: Lactobacillus delbrueckii subsp. bulgaricus, originating from yogurt. So, the study of vaginal lactobacilli could also be seen as a study on the basics of the genus Lactobacillus and what makes this group so important for human health.

At present, it is not well understood why lactobacilli dominate the human vagina under healthy conditions. Interestingly, this appears to be the case only in humans and not in other mammals. We speculate that it is because lactobacilli have beneficial functions and, when transmitted from mother to infant in early life, have a peculiar capacity to inhibit dangerous pathogens for our offspring, including group B streptococci, Enterobacteriaceae, fungi and various viruses. Lactobacilli also have interesting immune modulatory capacities. A rather unique feature in humans is the menstrual cycle and the estrogen-stimulated production of glycogen being a major sugar source for the lactobacilli in the vagina, resulting in high production of lactic acid, an excellent antimicrobial molecule against numerous pathogens. But the short answer is that we have no really clear answer to these fundamental questions of human biology.

Because the ERC funding allows us to be a bit more aspirational than in our usual research endeavors, we decided to address some of these questions by engaging women as citizen scientists. So we launched an ambitious citizen science project on vaginal lactobacilli and women’s health, named the Isala Project (see www.isala.be — it’s only in Dutch, but easily translatable with Google Translate 😊). The project is named after Isala Van Diest (1842-1916), the very first female physician in Belgium.

Our initial ambition was to ask 200 healthy women at different points in their menstrual cycle to provide vaginal swabs for microbiome sequencing and culture of lactobacilli. Our plan was to launch the call for volunteers on International Women’s Day (March 8, 2020), but COVID-19 made us revise our plans. We postponed our call until March 24, realizing that most women were at home during the lockdown. We assumed that since the national news was dominated by the SARS-CoV-2 virus, it was going to be difficult to reach out with traditional news channels. However, within two weeks, more than 5500 women registered for Isala on our website and we even had to restrict sign-ups!

We thought many women would still drop out if they found out they had to fill in an extensive questionnaire with intimate and lifestyle-related questions, but this was not the case. Almost 4700 women filled out the extensive questionnaire, demonstrating strong enthusiasm, commitment, and engagement. We decided to send a self-sampling kit to all the women who had filled in the entire questionnaire and supplied their postal address. Over the summer, we sent 4100 self-sampling kits, and of these, 80% of the women have already sent back their swabs to us. Our lab members are overjoyed with the citizen science enthusiasm!

Even though managing the logistics of the postal packages was a huge administrative challenge, we managed to keep everything straight. Thanks to an amazing team of dedicated and super-organized PhD students, lab techs, postdocs, master students, clinicians, bio-informaticians, statisticians, and communication partners, we can now say that we are around halfway through the project. We have been able to process all swabs that arrived to DNA extracts (for microbiome sequencing) and glycerol stocks (for the lactobacilli biobank and metabolomics later). Within the next months, these samples will be run on our MiSeq for 16S rRNA amplicon sequencing; the functional, genetic, and metabolomic characterization will of course take much more time. Making vaginal microbiome profiles for all these citizen scientists by next spring is now our priority, as we want to send all participants a personal update by then.

With this project, we are also changing up the traditional publication timeline: we are communicating about the process while not having all the results yet. We will inform the participants about their microbiome profiles before we submit or publish the related peer-reviewed manuscripts. This is because we want to actively communicate with our participants, opening discussions on the topic — and empowering women, without delay, to think about their vaginal health. We even have suggested conversation starters on our website and in the sampling boxes.

Time will tell whether these efforts will pay off for women’s health! Citizen Science can sometimes be surprising, but so far, we are very happy with the contact we’ve made with our committed and enthusiastic participants. We even have a hashtag, ‘#LetsSwab for the future’. I highly encourage my fellow scientists to consider organizing citizen science projects on topics related to the human microbiome, probiotics and prebiotics, because it is a unique way to get inspired and to do research on a large scale.

 

EFSA’s QPS committee issues latest updates

/in ISAPP Science Blog /by KC

By Bruno Pot, PhD, Vrije Universiteit Brussel and Mary Ellen Sanders, PhD, Executive Science Officer, ISAPP

On July 2nd, the European Food Safety Authority (EFSA) published the 12th update of the qualified presumption of safety (QPS) list, a list of safe biological agents, recommended for intentional addition to food or feed, covering notifications from October 2019-March 2020. It was good news to all stakeholders to see that EFSA discussed the recent taxonomic changes within the genus Lactobacillus (see ISAPP blog here) as well as addressed some microbes being considered as potential, novel probiotics.

What is QPS?

In 2005 EFSA established a generic approach to the safety assessment of microorganisms used in food and feed, prepared by a working group of the former Scientific Committee on Animal Nutrition, the Scientific Committee on Food and the Scientific Committee on Plants of the European Commission. This group introduced the concept of “Qualified Presumption of Safety” (QPS), which described the general safety profile of selected microorganisms. The QPS process was mainly developed to provide a generic pre‐evaluation procedure harmonized across the EU to support safety risk assessments of biological agents performed by EFSA’s scientific panels and units. A QPS assessment is performed by EFSA following a market authorisation request of a regulated product requiring a safety assessment. Importantly, in the QPS concept, a safety assessment of a defined taxonomic unit is performed independently of the legal framework under which the application is made in the course of an authorisation process.

QPS status is granted to a taxonomic unit (most commonly a species), based on reasonable evidence. A microorganism must meet the following four criteria:

1.       Its taxonomic identity must be well defined.

2.       The available body of knowledge must be sufficient to establish its safety.

3.       The lack of pathogenic properties must be established and substantiated (safety).

4.       Its intended use must be clearly described.

Any safety issues, noted as ‘qualifications’, that are identified for a species assessed under QPS must be addressed at the strain or product level. Microorganisms that are not well defined, for which some safety concerns are identified or for which it is not possible to conclude whether they pose a safety concern to humans, animals or the environment, are not considered suitable for QPS status and must undergo a full safety assessment. One generic qualification for all QPS bacterial taxonomic units is the need to establish the absence of acquired genes conferring resistance to clinically relevant antimicrobials (EFSA, 2008).

If an assessment concludes that a species does not raise safety concerns, it is granted “QPS status”. Once EFSA grants a microorganism QPS status, it is included on the “QPS list” and no microorganism belonging to that group needs to undergo a full safety assessment in the European Union.

The QPS list is re‐evaluated every 6 months by the EFSA Panel on Biological Hazards based on three “Terms of Reference” (ToR)*. This evaluation is based on an extensive literature survey covering the four criteria mentioned above.

What happened to the genus Lactobacillus?

In April 2020, based on a polyphasic approach involving whole genome sequencing of more than 260 species of the former genus Lactobacillus, the genus was reclassified into 25 genera including the emended genus Lactobacillus, which includes host-adapted organisms that have been referred to as the L. delbrueckii group, the earlier described genus Paralactobacillus as well as 23 novel genera, named Acetilactobacillus, Agrilactobacillus, Amylolactobacillus, Apilactobacillus, Bombilactobacillus, Companilactobacillus, Dellaglioa, Fructilactobacillus, Furfurilactobacillus, Holzapfelia, Lacticaseibacillus, Lactiplantibacillus, Lapidilactobacillus, Latilactobacillus, Lentilactobacillus, Levilactobacillus, Ligilactobacillus, Limosilactobacillus, Liquorilactobacillus, Loigolactobacilus, Paucilactobacillus, Schleiferilactobacillus, and Secundilactobacillus. Read more in the original paper here or on the ISAPP blog here).

These name changes could have considerable economic, scientific and regulatory consequences, as discussed during an expert workshop organised by the Lactic Acid Bacteria Industrial Platform (LABIP). One of the points discussed during this workshop was the possible implication of the name change on the QPS list in Europe and the FDA’s GRAS list in the USA.

What did EFSA do?

In a 42-page document, which can be found here, amongst others, the species of the former genus Lactobacillus that were already listed on the QPS list, have been formally renamed at the genus level. The species names remained the same, as the taxonomic revision from April 2020 only affected the genus name. As a result, the genus names of 37 former Lactobacillus species on the QPS were updated, and now span 13 different genera. Table 1 delineates these nomenclature updates.

Table 1: Taxonomic revision of the 37 species formerly of the Lactobacillus genus present on the QPS list (published here).

Earlier denomination                                                      Updated denomination
Lactobacillus acidophilus                     Lactobacillus acidophilus
Lactobacillus alimentarius Companilactobacillus alimentarius
Lactobacillus amylolyticus Lactobacillus amylolyticus
Lactobacillus amylovorus Lactobacillus amylovorous
Lactobacillus animalis Ligilactobacillus animalis
Lactobacillus aviarius Ligilactobacillus aviarius
Lactobacillus brevis Levilactobacillus brevis
Lactobacillus buchneri Lentilactobacillus buchneri
Lactobacillus casei Lacticaseibacillus casei
Lactobacillus collinoides Secundilactobacillus collinoides
Lactobacillus coryniformis Loigolactobacillus coryniformis
Lactobacillus crispatus Lactobacillus crispatus
Lactobacillus curvatus Latilactobacillus curvatus
Lactobacillus delbrueckii Lactobacillus delbrueckii
Lactobacillus dextrinicus Lapidilactobacillus dextrinicus
Lactobacillus diolivorans Lentilactobacillus dioliovorans
Lactobacillus farciminis Companilactobacillus farciminis
Lactobacillus fermentum Limosilactobacillus fermentum
Lactobacillus gallinarum Lactobacillus gallinarum
Lactobacillus gasseri Lactobacillus gasseri
Lactobacillus helveticus Lactobacillus helveticus
Lactobacillus hilgardii Lentilactobacillus hilgardii
Lactobacillus johnsonii Lactobacillus johnsonii
Lactobacillus kefiranofaciens Lactobacillus kefiranofaciens
Lactobacillus kefiri Lentilactobacillus kefiri
Lactobacillus mucosae Limosilactobacillus mucosae
Lactobacillus panis Limosilactobacillus panis
Lactobacillus paracasei Lacticaseibacillus paracasei
Lactobacillus paraplantarum Lactiplantibacillus paraplantarum
Lactobacillus pentosus Lactiplantibacillus pentosus
Lactobacillus plantarum Lactiplantibacillus plantarum
Lactobacillus pontis Limosilactobacillus pontis
Lactobacillus reuteri Limosilactobacillus reuteri
Lactobacillus rhamnosus Lacticaseibacillus rhamnosus
Lactobacillus sakei Latilactobacillus sakei
Lactobacillus salivarius Ligilactobacillus salivarius
Lactobacillus sanfranciscensis Fructilactobacillus sanfranciscensis

EFSA further specifies that “To maintain continuity within the QPS list, all the strains belonging to a previous designed Lactobacillus species will be transferred to the new species. Both the previous and new names will be retained”. (Emphasis added.)

Impact of the QPS update on the probiotic field

The probiotic field can also take note of this current update for its review of two ‘next generation’ probiotic species evaluated for possible QPS status, Akkermansia muciniphila and Clostridium butyricum.  Akkermansia muciniphila has been actively researched as a probiotic to help manage metabolic syndrome (Depommier et al. 2019). A probiotic preparation containing both Akkermansia muciniphila and Clostridium butyricum has been studied in a randomized controlled trial for postprandial glucose control in subjects with type 2 diabetes (Perraudeau et al 2020). The committee’s decisions:

  • Akkermansia muciniphila is not recommended for QPS status due to safety concerns;
  • Clostridium butyricum is not recommended for QPS status because some strains contain pathogenicity factors; this species is excluded for further QPS evaluation.

The publication of the next scientific opinion updating the QPS list is planned for December 2020, based on the 6-month assessments carried out by the BIOHAZ Panel.

Conclusion

Due to its scientific rigor and continuous updates, the EFSA QPS efforts provide useful perspective for the global scientific community on safety of candidate microbes for use in foods. Their embrace of the new taxonomic status of lactobacilli signals to other stakeholders that it is time to start the process of doing the same. Further, their assessment of species being proposed and studies as ‘next generation’ probiotics is an important reminder that a microbe’s status as a human commensal is not a guarantee of its safety for use in foods.

 

*QPS Terms of Reference (ToR) (quoted from here):

ToR 1: Keep updated the list of biological agents being notified in the context of a technical dossier to EFSA Units such as Feed, Pesticides, Food Ingredients and Packaging (FIP) and Nutrition, for intentional use directly or as sources of food and feed additives, food enzymes and plant protection products for safety assessment.

ToR 2: Review taxonomic units previously recommended for the QPS list and their qualifications when new information has become available. The latter is based on a review of the updated literature aiming at verifying if any new safety concern has arisen that could require the removal of the taxonomic unit from the list, and to verify if the qualifications still efficiently exclude safety concerns.

ToR 3: (Re)assess the suitability of new taxonomic units notified to EFSA for their inclusion in the QPS list. These microbiological agents are notified to EFSA and requested by the Feed Unit, the FIP Unit, the Nutrition Unit or by the Pesticides Unit.

 

How some probiotic scientists are working to address COVID-19

/in ISAPP Science Blog, News /by KC

By ISAPP board of directors

With the global spread of COVID-19, the scientific community has experienced an unusual interruption. Across every field, many laboratories are temporarily shuttered and research programs of all sizes are on hiatus. Principal investigators around the world are doing their part to keep their students and local communities safe, and many are donating lab safety equipment to medical first responders who urgently need it.

In this global circumstance of research being put on hold, it is enlightening to consider what some scientists in the fields of probiotics, prebiotics, and fermented foods are working on—or proposing—in the context of understanding ways to combat viral threats. These individuals are rising to the scientific challenge of finding effective ways to prevent or treat viral infections, which may directly or indirectly contribute to progress against SARS-CoV-2.

Here, ISAPP shares words from some of these scientists—and how they have connected the dots from probiotics to coronavirus-related work with potential medical relevance.

Prof. Sarah Lebeer, University of Antwerp, Belgium: Relevance of the airway microbiome profile to COVID-19 respiratory infection and using certain lactobacilli to enhance delivery or efficacy of vaccines

Could the microbes in our upper and lower airways play a role in how we respond to the virus? Significant individual differences exist in the microbes that are prevalent and dominant in our airways. Lactobacilli are found in the respiratory tract, especially in the nasopharynx. They might originate there from the oral cavity via the oronasopharynx, but we have found some strains that seem to be more adapted to the respiratory environment, for example by expressing catalase enzymes to withstand oxidative stress. Currently we have a Cell Reports paper in press that shows certain lactobacilli are more prevalent in the upper respiratory tract of healthy people compared to those with chronic rhinosinusitis. Further investigation of one strain found in healthy people showed it inhibited growth and virulence of several upper respiratory tract pathogens. Our work on other viruses shows that certain lactobacilli can even block the attachment of viral particles to human cells. This raises the possibility that lactobacilli could be supplemented through a local spray to help improve defenses against the inhaled virus. Based on these data, we are initiating an exploratory study with clinicians and virologists on whether specific strains of lactobacilli in the nasopharynx and oropharynx could have potential to reduce viral activity via a multifactorial mode of action, including barrier-enhancing and anti-inflammatory effects, and reduce the risk of secondary bacterial infections in COVID-19.

Another line of exploratory research from our lab pertains to the delivery or efficacy of SARS-CoV-2 vaccines. Currently, many groups are rapidly developing vaccines, which predominantly use the viral spike S protein or its receptor-binding domain as antigen to induce protective immunity. We are exploring the potential of specific strains of lactobacilli with immunostimulatory effects as adjuvants for intranasal SARS-CoV-2 vaccination, or the potential of a genetically engineered antigen-producing organism for vaccine delivery.

At this year’s virtual ISAPP annual meeting, Dr. Karen Scott and I will also be leading an ISAPP discussion group called “How your gut microbiota can help protect against viral infections”. We will discuss previous work that has shown bacteria can have anti-viral effects. For many years, our colleagues, Profs. Hania Szajewska and Seppo Salminen, have studied a different virus, namely rotavirus, that causes acute diarrhea in children, and have found that Lactobacillus rhamnosus GG (new taxonomy Lacticaseibacillus rhamnosus GG) binds rotavirus and disables it, thereby blocking viral infection/multiplication. This may explain why this probiotic reduces the incidence and duration of acute diarrhea in children. Similar findings have been reported for specific probiotics and prebiotics and prevention of upper respiratory tract infections.

Prof. Rodolphe Barrangou, North Carolina State University, USA: Engineering probiotic lactobacilli for vaccine development

Between NC State University and Colorado State University (CSU) there is a historical collaborative effort aiming at engineering probiotics to develop novel vaccines. The intersection of probiotics and antivirals is the focus here with expressing antigens on the cell surface of probiotics to develop oral vaccines. The CSU infectious diseases center is very much fully operational and focused on COVID-19 now, and we recently received a research exception to open our lab for two individuals assigned to this NIH-funded project, and pivot our rotavirus efforts here to coronavirus. We are actively engineering Lactobacillus acidophilus probiotics expressing COVID-19 proteins to be tested as potential vaccines at CSU in the near future, as progress dictates.

Prof. Colin Hill, University College Cork, Ireland: The microbiome as a predictor of COVID-19 outcomes

We have recently proposed a project to examine oral and faecal microbiomes to identify correlations/associations between COVID-19 disease severity and individual microbiome profiles. If funded, we propose to analyse bacterial and viral components of the microbiome from three body sites (nasopharyngeal swabs, saliva, and faeces) in 200 donors and mine the data for biomarkers of disease risk and clinical severity. We will use machine learning to identify microbiome signatures in patients who contract the virus and remain asymptomatic, those who develop a mild infection, or those who have an acute infection requiring admission to an intensive care unit and intubation. This will enable microbiome-based risk stratification of subjects testing positive, and appropriate clinical management and early intervention, and prioritization of subjects for receiving an eventual vaccine.

Dr. Dinesh Saralaya, Bradford Institute for Health Research, UK: A live biotherapeutic product for targeted immunomodulation in COVID-19 infection

The COVID-19 pandemic presents an unprecedented challenge to our healthcare systems and we desperately require the rapid development of new therapies to ease the burden on our intensive care units. As well as its appropriate mechanism of action (targeted immunomodulation rather than broad immunosuppression), the highly favourable safety profile of MRx-4DP0004 makes it a particularly attractive candidate for COVID-19 patients, and may potentially allow us to prevent or delay their progression to requiring ventilation and intensive care.

The trial is a Phase II randomised, double-blind, placebo-controlled trial to evaluate the efficacy and safety of oral Live Biotherapeutic MRx-4DP0004 in addition to standard supportive care for hospitalised COVID-19 patients. Up to 90 subjects will be randomised 2:1 to receive either MRx-4DP0004 or placebo (two capsules, twice daily) for 14 days. The primary endpoint is change in mean clinical status score as measured by the WHO’s 9-point Ordinal Scale for Clinical Improvement, while secondary endpoints include a suite of additional measures of clinical efficacy such as need for and duration of ventilation, time to discharge, mortality, as well as safety and tolerability. The size and design of the trial are intended to generate a meaningful signal of clinical benefit as rapidly as possible.

Drs. Paul Wischmeyer and Anthony Sung, Duke University School of Medicine, USA: Probiotics for prevention or treatment of COVID-19 infection

We are planning several randomized clinical trials of probiotics in COVID-19 prevention and treatment. These trials are based on multiple randomized clinical trials and meta-analyses that have shown that prophylaxis with probiotics may reduce upper and lower respiratory tract infections, sepsis, and ventilator associated pneumonia by 30-50%. These benefits may be mediated by the beneficial effects of probiotics on the immune system. The Wischmeyer laboratory and others have shown that probiotics, such as Lactobacillus rhamnosus GG, can improve intestinal/lung barrier and homeostasis, increase regulatory T cells, improve anti-viral defense, and decrease pro-inflammatory cytokines in respiratory and systemic infections. These clinical and immunomodulatory benefits are especially relevant to individuals who have developed, or are at risk of developing, COVID-19. COVID-19 has been characterized by severe lower respiratory tract illness, and patients may manifest an excessive inflammatory response similar to cytokine release syndrome, which has been associated with increased complications and mortality. We hypothesize that probiotics will directly reduce COVID-19 infection risk and severity of disease/symptoms. Thus, we are proposing a range of trials, the first of which will be:

A Randomized, Double-Blind, Placebo-Controlled Trial of the PRObiotics To Eliminate COVID-19 Transmission in Exposed Household Contacts (PROTECT-EHC). Objective: Prevent infection and progression of illness in household contacts/caregivers of known COVID-19 patients exposed to COVID-19 (who have a >20-fold increased risk of infection). We will conduct a multicenter, randomized, double blind, phase 2 trial of the probiotic Lactobacillus rhamnosus GG vs. placebo to decrease infections and improve outcomes. This trial will include weekly collection of microbiome samples from multiple locations (i.e. fecal, oral). This trial will utilize a commercial probiotic, delivering 20 billion CFU of Lactobacillus rhamnosus GG, and placebo.

We are currently developing protocols to study prevention and treatment of COVID-19 in a range of other at-risk populations including: 1) Healthcare providers; 2) Hospitalized patients; 3) Nursing home and skilled nursing facilities workers. We are seeking additional funding and potential collaborators/trial sites for this work, and encourage interested funders and collaborators to reach out for further information or to join the effort at: Paul.Wischmeyer@nullduke.edu and also encourage you to follow our progress and our other probiotic/microbiome work on Twitter: @paul_wischmeyer

Prof. Gregor Reid, University of Western Ontario, Canada: Documenting anti-viral mechanisms of certain probiotic strains

While our institute is now studying the cytokine storm in COVID-19 patients, the closure of my lab has meant I have turned to surveying the literature: Prof. Glenn Gibson and I have a paper published in Frontiers in Public Health stating a case for probiotics and prebiotics to help ‘flatten the curve’ and keep patients from progressing to severe illness. There is good evidence that certain orally administered probiotic strains can reduce the incidence and severity of viral respiratory tract infections. Mechanistically this appears to be, in part, through modulation of inflammatory responses similar to those causing severe illness in COVID-2 patients, and antiviral activity — which has not been shown against SARS-Co-V2 but has been documented against common respiratory viruses, including influenza, rhinovirus and respiratory syncytial virus. Improving gut barrier integrity and affecting the gut-lung axis may also be part of these probiotics’ mechanism of action. At a time when drugs are being tried with little or no anti-COVID-19 data, probiotic strains documented for anti-viral, immunomodulatory and respiratory activities should be considered for clinical trials to be part of the armamentarium to reduce the burden and severity of this pandemic.

Rapid, collaborative effort

As the world waits in ‘lockdown’ mode, continued scientific progress for coronavirus prevention or treatment is critically important. ISAPP salutes all probiotic and prebiotic scientists who are stepping up to pursue unique solutions. Addressing the important research questions described above will require a rapid collaborative effort, from obtaining ethical approval and involving medical staff to collecting the samples, to recruiting participants as well as experts to process and analyze samples. All of this has to be done in record time – but from our experience of this scientific community, it’s definitely up to the challenge.

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.

Highlighting the importance of lactic acid bacteria: An interview with Prof. Seppo Salminen

/in Consumer Blog, ISAPP Science Blog /by KC

By Kristina Campbell, M.Sc., science & medical writer

 

In a 2009 book called What on Earth Evolved?, British author Christopher Lloyd takes on the task of ranking the top 100 species that have influenced the planet throughout its evolutionary history.

What comes in at number 5, just slightly more influential than Homo sapiens? Lactobacilli, a diverse group of lactic-acid-producing bacteria.

The influential status of these bacteria on a global scale comes as no surprise to Prof. Seppo Salminen, ISAPP president and Professor at University of Turku (Finland), who has spent most of his career studying these microbes. He is the co-editor of the best-selling textbook Lactic Acid Bacteria: Microbiological and Functional Aspects, the fifth edition of which was released earlier this year. Salminen says the scientific community has come a long way in its understanding of lactic acid bacteria (LAB)—and in particular, lactobacilli.

Seppo Salminen at ISAPP annual meeting 2019

“If you think about the history of humankind, earlier on, more than 60% of the food supply was fermented,” explains Salminen. “On a daily basis, humans would have consumed many, many lactic acid bacteria.”

Yet 30 years ago when Salminen and his colleagues published the first edition of the textbook on lactic acid bacteria, they were working against perceptions that bacteria were universally harmful. The science on using live microorganisms to achieve health benefits was still emerging.

“Most people in food technology, they had learned how to kill bacteria but not how to keep them alive,” he explains. “They didn’t yet know how to add them to different formulations in foods and what sort of carrier they need. At that time, the safety and efficacy of probiotics was not well understood.”

Around ten years later, scientists came together to develop a definition of probiotics on behalf of the Food and Agriculture Organization of the United Nations and the WHO (FAO/WHO)—in a report that formed the basis of ISAPP Consensus meeting and today’s international consensus definition: “live microorganisms that, when administered in adequate amounts, confer a health benefit on the host”.

With probiotics having been more precisely defined, the following years were a time of rapid scientific progress in the field. Lactobacilli became the stars of the show, as research emerged on the benefits of various strains and combinations of strains in food science and medicine.

Fast forward to today, when rapidly expanding gut microbiome research adds another dimension to what we know about these bacteria. While lactic acid bacteria are still primarily of interest for the health benefits they impart, scientists can now also study their interactions with other microorganisms in the intestinal microbiome. In some cases, this kind of research may help uncover new mechanisms of action.

After everything Salminen and his textbook co-editors (Vinderola, Ouwehand, and von Wright) have learned about lactic acid bacteria over the past few decades, Salminen says there are two main reasons for the perennial importance of the bugs. “One is their importance in food fermentation, extending the shelf life of foods, making a kind of food processing or ‘agricultural processing’ possible. To make sauerkraut shelf-stable for weeks, or to make yogurt or cheese.”

The second reason, he says, relates to their benefits for the host. “Lactic acid bacteria, especially lactobacilli, reinforce intestinal integrity. So they protect us against pathogens; and sometimes against toxins and heavy metals by binding them away.”

He continues, “The more we know, the more we understand that LAB are needed. There are very specific strains that are helpful in different conditions for animal feeds or for clinical nutrition for infants, for example.” He says the knowledge is expanding at such a rapid pace that it may only be a few more years before the textbook he co-edited will need another edition.

Salminen is currently one of the world’s most cited probiotic researchers, and has diverse ongoing research projects related to digestive health, eczema, early life, and nutrition economics—but lactic acid bacteria are the thread that weaves everything together.

“I’m proud to be working on the fifth most important factor in human evolution,” he says.