05 July 2021- It can be hard to wrap your head around the scale of the microbiota. Trillions upon trillions of bacteria, fungi, viruses, and other microbes live in symbiosis with animals. In the case of the human body, it has even been estimated by some that the cells of the microbiome outnumber those with actual human DNA. The idea of influencing this vast universe by tinkering with a couple of critical species sounds almost a bit ridiculous, and yet it happens routinely with the use of probiotics, prebiotics, or other additives. But how?
Answering that question meaningfully requires turning to the various disciplines within computational biology which are known as the omics sciences, an area in which Lallemand Animal Nutrition has increasingly been building its expertise.
As explained by Dr. Emmanuelle Apper, who leads the mechanistic research around microbiota at Lallemand Animal Nutrition, the omics disciplines are useful because they aim to quantify and characterise pools of different molecules (genetic, metabolic, etc.), and translate this into structure or function. Or, to put it another way, to understand exactly what microbes are there, what they’re doing, and how they influence the phenotype (what we can actually see at an animal level in terms of performance and health).
“Lallemand has been investing in metagenomics for decades in this particular area, and with increasing precision, because it provides relevant metrics to measure the power of the microbiota (for example, the population of different microbes as a proportion of the total, expression of different genes, etc.) throughout the digestive tract: in the rumen and in the lower gut,” explains Laurent Dussert, Ruminant category manager at Lallemand. |
Laurent Dussert |
Bridging the gap between microbiome and animal performance
It is important to understand that this is not merely hypothetical, something which could possibly tie into animal nutrition someday. According to Lallemand, the industry is already benefitting from the understanding that a serious focus on metagenomics analysis has made possible.
Dr. Caroline Achard |
One area of particular interest is metagenomics’s role in clarifying the mode of action of products which exist primarily to influence the microbiome, such as probiotics. “Today, we are already able to see the effects of our products on the composition of the microbiota, and now we’d like to go further and to improve our knowledge about the mode of action,” says Dr. Caroline Achard, research scientist at the Lallemand Monogastric Center of Excellence in Toulouse. |
“We had a look at the impact of this supplementation on the stability of the microbiota during farrowing, because it’s a [transitional period] that will create a lot of variation and change in the microbiota,” recounts Dr. Apper. “And after that we also followed the piglets, which did not receive yeast, and their microbiota. Even after weaning, we saw maternal imprinting. So it means that the fact we gave some yeast to the mother resulted in a “printing” of the microbiota of the piglets, which lasted even after weaning. We specifically saw an effect on Fibrobacteres phylum, well-known for its fibrolytic activity. These were quite new results in swine and we submitted a patent last year based on those results.”
Indeed, as her colleague Pierre Lebreton, monogastrics marketing and technical manager, adds, being able to clearly explain—and potentially optimize—the effects of products such as yeast is critical if the industry truly hopes to meet its goals of moving away from antibiotics and zinc oxide while respecting animal welfare. “Metagenomics has been really helpful to express and prove that intestinal microbial composition can be effectively regulated with S. boulardii even through a Campylobacter challenge in broilers; that can be taken as a model for any other microbial perturbation we may face on farm (Massacci et al, 2019).” However, he is insistent that research into omics analyses is about more than developing fancy new gadgets for understanding the mode of action of feed additives. “All those new techniques represent new tools to clarify, understand and sometimes modify basal animal physiology and requirements. They are not only a description of product’s mode of action, but more than that, it’s about understanding global gut microbiota’s impacts on animal welfare, health and efficiency.” |
Pierre Lebreton |
Big questions going forward
Looking ahead, it is also easy to see the application of metagenomic research for personalized nutrition. “It is still difficult to know what makes for a good microbiota,” says Dr. Apper. “We already know it will be very variable from one animal to another, from one farm to another, so we have to deal with that [variability].” Indeed, as she points out, it might even turn out that a “good” microbiota is not ultimately defined by who makes up the microbial populations, but rather by what they are doing. “We know that we may have different composition [in the microbiomes of animals] but have overlap in terms of functions.”
“We need to generate a lot of data, maybe at different critical stages, like weaning, like farrowing, and to see what happens, what is the impact of different products… after that we are convinced that we will be more accurately able to respond to the problems of animal production.”
Yet another ambition of the bioinformatics research teams is the discovery of biomarkers. As explained by Dr. Achard, “There are some specific ways to analyse the data that allows us to correlate the microbial composition to other zootechnical performance, such as performance, growth, feed intake or feed conversion, and doing that, we may be able to identify key bacteria within the microbiota which are linked with optimal performance.”
Of course, this is something of a simplification of an idea which is still very much in its infancy. As Dr. Achard points out, a lot of work is still needed to refine and standardise the statistical models used in metagenomic analysis—and when it comes to this discipline, statistical interpretation is everything. “It’s not always easy to extrapolate the data [generally] to other farms; the more data you are generating, the more confident you can be in your conclusion. This prediction step is still not so easy, but in the end, this is where we would like to go.”
“Ideally it would be really nice to be able to analyse my computer and based on a few biomarkers, to be able to predict the performance of the animal, or to be able to say ‘ok, we know that we can apply this probiotic, this product, and we will have a nice response.’”
Life on the leading edge of omics research
The challenge Lallemand has set itself in metagenomics is two-fold.
Dr. Emmanuelle Apper
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One, as discussed above, is putting these insights at the service of the animal nutrition market. Beyond the research work discussed above, the company is also getting involved in educating the industry about these topics. “There is more and more discussion on omics and things move fast in this area,” notes Dr. Apper. “In order to help our teams in the field, as well as partners whose primary expertise is not in the area of genomics, to appreciate the implications of the work going on in omics, we are putting together an educational booklet that describes the principle of these techniques and gives an overview of the latest findings in the different animal species from the point of view of nutrition.” |
Dr. Achard—who is herself one such researcher working in this environment—confirms that the system has been extremely valuable in a domain which is changing by the day. “What is really important for me is to be able to discuss and exchange with my peers about the best way to analyse the data, because as we mentioned before, the field is still evolving, there is a lot of scientific publications, and we really need to think very critically about the statistical methods that are used, to be able to use these methods, and to be able to choose the method which would be appropriate to analyse the whole data set.”
Finally, the company is also extending its metagenomics understandings to areas outside the gut. “The gut microbiome is not the only one. We also study the microbiome in feeds—like in silage—and we have a new field of research with biofilm in the environment of the farm, and in the manure… and even water bioremediation research for aquaculture production,” Dr. Apper shares. “This is also new and I’m sure that it will become a more and more important field of research within metagenomics and omics.”
“It’s looking at microbiomes, with an “S”… and there’s more and more of them.”
Published in association with Lallemand Animal Nutrition