Figure 2: Novel mode of action framework for modulating core microbiome pathways to achieve consis- tent benefits for growers.


Core metagenomic pathways We learn early on in animal biology that certain metabolic functions, like glycolysis and the TCA cycle, are highly con- served across different species. These conserved pathways provide the foundation for basic biological functions, such as growth and homeostasis. The key insight we gain from study- ing metagenomics is that the same principle holds for micro- organisms. Often the genes to make a given metabolite are redundant across many different microbes. This redundancy is the recipe for consistency: two microbiomes can be func- tionally equivalent even when they have vastly different mi- crobial profiles. Returning to our analogy: you can swap vari- ous musicians in and out of the orchestra, but the ensemble can still play the same music. In our own work with whole-genome sequencing, we observe repeatedly that many metabolic functions of the microbiome remain conserved between birds with wildly different micro bial profiles. Broadly speaking, these core microbiome pathways tend to involve central carbon and nitrogen utilisation, such as carbohydrate, lipid, amino acid and nucleotide metabolism. Certainly aspects of microbial carbon metabolism, such as short-chain fatty acid (SCFA) production, have been recognized for decades. Propionate is upgraded by host gluconeogenesis to create additional metabolic energy. Butyrate directly nourish- es the gut epithelium, among many other roles. SCFAs may in- terface with host regulatory functions, such as immune signal- ing and the pancreatic hormone regulatory network. Nitrogen utilisation pathways control the degradation and bio synthesis of peptides. Amino acids synthesized by the micro biome can be absorbed by the bird to increase effective protein availability. In animal production, adverse protein fer- mentation may generate excess ammonia, biogenic amines, and nitrogenous toxins that degrade barrier function, trigger inflammation, reduce welfare and increase environmental impact.


New take on mode of action Poultry science has long targeted the microbiota with gut- health products: direct fed microbials (DFMs), essential oils, organic acids, prebiotics and NSPases, to name a few. These products have their merits but they all suffer from a key weakness. Their modes of action are fundamentally grounded in microbial taxonomy, tying them to the inherent variability of microbial composition. Prebiotics and/or fiber-digesting enzymes provide additional fermentable carbon to the microbiota. But do the microbiota use that carbon wisely? Pro biotics add bacteria with anticipated benefits. But what if the existing ecology or chemical environment prevents those organisms from acting as intended? Returning to our analogy: you can hire great musicians, give them a nice venue and even feed them a healthy lunch. But without a conductor, the quality and consistency of the music will vary considerably. The same is true of the microbiome. If we want consistency, we must provide a conductor to direct function, and modern microbiome science tells us how. There is potential to influ- ence microbial gene expression for targeted pathways, or ac- tivate/deactivate microbial enzyme pathways, to name only two. This idea of microbiome metabolic modulation is, at the same time, simple and a radically new framework for mode of action (Figure 2). Our goal is a new category of precision feed additives that act on core metagenomic functions to induce targeted effects with unprecedented consistency. Imagine if we could reliably modulate microbiome pathways to improve the health, per- formance, welfare and sustainability of poultry production. Hold that thought and stay tuned.


References available on request. ▶ POULTRY WORLD | No. 7, 2020 25


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