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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.

Episode 10: How the ISALA project investigates what makes a healthy vaginal microbiome

/in Podcast, Season One /by KC

Podcast: Play in new window | Download

Subscribe: Apple Podcasts | Spotify | RSS

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 Prebiotic (ISAPP), a nonprofit scientific organization dedicated to advancing the science of these fields.

How the ISALA project investigates what makes a healthy vaginal microbiome, with Prof. Sarah Lebeer

Episode summary:

In this episode, the ISAPP hosts discuss what’s known about the healthy vaginal microbiome with Prof. Sarah Lebeer from University of Antwerp, Belgium. Lebeer describes the citizen science project she leads in Belgium called “ISALA” and outlines its findings to date. She also talks about important questions remaining to be answered in the field.

Key topics from this episode:

  • The importance and difficulties of leading a citizen science project.
  • How the ISALA project is expanding with sister-like citizen science projects around the world.
  • Research on the vaginal microbiota is important and fascinating, with a lot of  opportunities and a lot of unanswered questions.
  • The role of vaginal microbiota in maintaining health and protecting against various infections such as sexually transmitted infections and urinary tract infections.
  • What we know about effects of nutrition, behavior, the menstrual cycle, and pregnancy on the composition of the vaginal microbiota, and the stability of vaginal microbes over time.
  • Transfer of vaginal species during infant delivery and initial microbial colonization of the baby. Do daughters inherit their vaginal microbes from their mothers?
  • How screening of vaginal lactobacilli may create targeted probiotic treatments for particular conditions.

 

Episode abbreviations and links:

ISALA project website (English)

Important probiotic trials focused on women’s health:

Sustained effect of LACTIN-V (Lactobacillus crispatus CTV-05) on genital immunology following standard bacterial vaginosis treatment: results from a randomised, placebo-controlled trial

Randomized Trial of Lactin-V to Prevent Recurrence of Bacterial Vaginosis

Effect of Oral Probiotic Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 on the Vaginal Microbiota, Cytokines and Chemokines in Pregnant Women

Efficacy and safety of vaginally administered lyophilized Lactobacillus crispatus IP 174178 in the prevention of bacterial vaginosis recurrence

Trials of vaginal microbiota transplantation:

Vaginal microbiome transplantation in women with intractable bacterial vaginosis

Additional resources:

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

 

About Prof. Sarah Lebeer:

Sarah Lebeer is a research professor at the Department of Bioscience Engineering of the University of Antwerp, Belgium. She has studied bioscience engineering, with a specialisation in cell and gene technology/food & health and obtained her Master at KU Leuven (Belgium). In 2008, she obtained a PhD degree with a topic on the mode of action of gastro-intestinal probiotics in inflammatory bowel diseases and a scholarship in the team of Prof. Jos Vanderleyden (KU Leuven). After a postdoc on the interaction between lactobacilli, viruses and mucosal immunology, in November 2011, she was offered a tenure track position at the University of Antwerp. Since then, she is leading the Laboratory for Applied Microbiology and Biotechnology of the ENdEMIC research group. In 2020, she was awarded with an ERC Starting Grant that enables her to gain more in-depth knowledge of the evolutionary history and ecology of lactobacilli (https://www.lebeerlab.com). This rationale was also an important driving force to revise the Lactobacillus genus taxonomy with  a large international consortium. Within the ERC project, Sarah has also launched the Isala citizen-science project to gain new insights in the role of vaginal lactobacilli for women’s health (https://isala.be). Since 2018, Sarah is an academic board member of the International Scientific Association on Probiotics and Prebiotics (www.isappscience.org). Communicating about beneficial microbes and probiotics for experts and laymen is an important inspiration for her daily work. 

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

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.