Speaker spotlight: Prof. Michael Gänzle on current directions in research on lactobacilli
Lactobacilli, a vast group of related bacteria found in the human body and throughout the natural environment, play a key role in food fermentations and are the most frequently studied bacteria associated with fermented foods.
When the genus Lactobacillus was overhauled into 25 separate genera in 2020 to better reflect genetic relationships and functional properties, one of those who led the reclassification was Prof. Michael Gänzle from University of Alberta, Canada. Prof. Gänzle has spent his career studying lactobacilli, and in particular, linking qualities of microorganisms (phylogeny, physiology and ecology) to fermented food properties and host health.
Prof. Gänzle will speak at ISAPP’s upcoming scientific symposium, held on 6th October in Tokyo, Japan, in a presentation titled “The phylogeny and ecology of lactobacilli determines their functionality in food fermentations”.
ISAPP connected with Prof. Gänzle to ask how research on lactobacilli has evolved over the past few decades, and what recent developments and future directions he plans to share during his presentation in Tokyo.
How did you first become interested in working on lactobacilli?
In my undergrad, I was fairly biochemically-minded. When I started my Master’s thesis in Walter Hammes’ lab, he was an expert on lactobacilli. I got hooked on metabolism of lactic acid bacteria, and remained hooked ever since.
The central question for me is: how can I convince lactobacilli in food fermentations to do what I want them to do? And to be able to convince them, I need to understand why they do what I want them to do.
You’ve authored hundreds of papers on digestion and fermented foods. What were some of the milestones in your understanding of lactobacilli throughout your career?
I wrote two articles in 2015. The first one was finished in February, and that was a purely biochemical description of metabolism of lactic acid bacteria. That was the first article that I explicitly stated we need to differentiate homo-fermentative and hetero-fermentative (based on the metabolic pathway they use to metabolise glucose) for the classification to make sense.
Probably no more than 4 weeks after that piece was submitted, my collaborator had the genome sequences of most type strains that were available at the time, and he sent me a core genome phylogenetic tree. The tree was a a treat – 16S rRNA gene phylogeny (evolutionary relationships) doesn’t reflect the phylogeny of the organisms. Core genome phylogeny was a new tool and, looking at the tree, I realized it’s a strict phylogenetic, separation: the heterofermentative lactobacilli are a distinct monophyletic clade (that is, a group of organisms with a single common ancestor) relative to all the other lactic acid bacteria. That was an Eureka moment for me. That second paper was published in the second half of 2015, making the case that metabolism and ecology are linked to phylogeny.
And then in 2020, the taxonomy change was largely anticipated by the 2015 paper.
What’s the next part of the story on lactobacilli that you’ll be sharing at the ISAPP meeting?
In the last 2 to 3 years, I’ve worked on domestication of lactobacilli, which also strongly builds on core genome phylogeny. The population structure of mesophilic dairy starter cultures, Lactococcus lactis subspecies lactis, the yogurt starter culture, Lactobacillus delbrueckii subspecies bulgaricus and the major organism in sourdough, Fructilactobacillus sanfranciscensis, is characterised by monophyletic clades, which are exclusively populated with isolates from fermented foods.
Knowing that these organisms are perpetually backslopped, the best possible conclusion is that these organisms were domesticated over thousands of years of backslopping. Humans have been fermenting dairy for about 7,000 years, a sufficient time for differentiation of intraspecific phylogenetic clades. We’ve fermented sourdough for 12,000 to 14,000 years, this time was sufficient for speciation.
That was a steep learning curve for me – as late as 2019, I’ve made the case that bacteria evolve so slowly that they’re unlikely to be domesticated. By reading up on the archaeological evidence, who fermented what when, who migrated from where to where, and which domestic animals were passed from west to east (dairy animals), or from east to west (chicken) across the Asian steppes, it occurred to me that the best way to explain this is domestication.
In your talk title, you mention both phylogeny and ecology. How do they relate to each other for lactobacilli?
In many cases, it’s a one-on-one match. If you say Fructilactobacillus, I know that it’s an insect-adapted organism. If you say Ligilactobacillus, for the most part, I know that I have to look in warm-blooded animals. The only problem is that humans have been too busy in isolating from humans, farm animals, and fermented foods, and they have not looked closely enough at the lactobacilli in the wild.
The “wild lactobacilli” may not bring any additional probiotic strains for human use, will enhance our knowledge on the phylogenetic and metabolic diversity of lactobacilli.
What do you hope people will take away from your ISAPP talk?
When I use the new taxonomy of lactobacilli in my undergrad class, I tell students that the new taxonomy is terrible if you don’t know lactobacilli very well, because instead of having to remember 3 genus names, you have to remember 37, including the neighboring and merged taxa. But if you know lactobacilli, and most of the people interested in probiotics are likely in that category, it’s great because if you know the genus name, and possibly the species name, you already know a whole lot about the phylogeny, the ecology, where to find it, and about the metabolism.
I hope to show people that metabolism and ecology are intricately linked to the phylogeny. If you’re selecting probiotic strains, or if you’re selecting strains for food fermentations, the genome sequence and taxonomy are important criteria to pick the right strains for specific applications.
When you think about future research on lactobacilli, do you think scientists will identify new health benefits?
I suspect that we know most of the health benefits, but we don’t know most of the mechanisms.
If you give me any genome sequence of, let’s say, Escherichia coli, I differentiate based on presence / absence of specific genes whether the strain is a harmless commensal or a terrible pathogen.
If you give me the genome sequence of a lactobacillus, I can’t make this prediction. There are a couple of metabolites that are known to contribute to probiotic traits, but the body of evidence is not nearly sufficient to confidently link genotype to health benefits.
What are the things you’re most excited about in the future of research on lactobacilli?
We are not even beginning to understand what lactobacilli do with phenolic compounds. Linking genes metabolism of phenolic compounds remains largely impossible. Several publications convincingly make the case that the health benefits of phytochemicals are not mediated by the phytochemicals themselves but by the bacterial metabolites of the phytochemicals. But which bacterial genes are responsible? That’s one area where I expect a bit of advance.
The second, I think we have to look more closely at the lactobacilli in the wild. I have a side project collecting ants and aphids, which are a good source of novel Fructilactobacillus species. One of my former students, now teaching in central Manitoba, is in contact with Indigenous hunters. When they hunt ducks and geese and rodents, we receive samples so that we can isolate Limosilactobacillus. I don’t quite know yet what we’ll get, but I’ll to pursue that further.
Prof Michael Gänzle will be presenting at the ISAPP Annual meeting in Tokyo on 6th October. This first day of the program features symposium plenary presentations and is open to general registration. Find out more and register here.
