Engineering the microbiome for animal health and conservation

Abstract

Considering the clear effects of microbiota on important aspects of animal biology and development (including in humans), this topic is timely and broadly appealing, as it compels us to consider the possibilities of altering the microbiome (without antibiotics) to positively affect animal health. In this review, we highlight three general approaches to manipulating the microbiome that have demonstrated success and promise for use in animal health. We also point out knowledge gaps where further inquiry would most benefit the field. Our paper not only provides a short and digestible overview of the current state of application, but also calls for further exploration of the microbial diversity at hand to expand our toolkit, while also leveraging the diversity and flexibility of animal systems to better understand mechanisms of efficacy.

Keywords: Probiotic; animal health; disease; dysbiosis; microbiome; microbiota transplant.

Figure 1.

(a) Conceptual diagram of adaptive shifts in the microbiome acting as an extension of host immunity. The trajectory of infection is influenced by propagule pressure or infectious dose (initial timepoint), and may progress rapidly toward a disease threshold (dashed line), or may progress more slowly. In both cases, the microbiome can respond to infection with adaptive shifts in the microbiome including changes in both alpha-diversity (line thickness), or beta-diversity (line color), with a propensity for dominance of members that can compete with the pathogen. Upon passing the disease threshold, the microbiome may become dysbiotic. Alternatively, immune responses in combination with adaptive microbiome shifts can reduce infection intensity leading to host recovery. Manipulation of the microbiome can hasten this natural process and give the host an advantage over the pathogen. (b) Principal coordinates plot of larval spotted salamander (Ambystoma maculatum) skin bacterial communities showing long-term effects of exposure to a pathogen or probiotic. While hosts resisted infection to the skin pathogen Batrachochytrium salamandrivorans (red), a shift in the microbiome was evident 35 days post-exposure compared to controls (yellow). Similarly, the probiotic Lysinibacillus sphaericus did not permanently establish on the host, yet the trajectory of the microbiome was shifted on the developing hosts (blue). Points are scaled by predicted anti-Batrachochytrium function of the community based on Woodhams et al. (antifungal function increased with probiotics, but was marginally significant; ANOVA, F_2,17 = 3.462, P = 0.055). While there was a disruption of the microbiome, dysbiosis is not indicated because function and stability remained consistent despite the shift in community structure. Data from Barnhart were re-analyzed with the QIIME2 pipeline using Deblur to pick sOTUs and unweighted UniFrac distance was calculated for use in the principal coordinates analysis. (A color version of this figure is available in the online journal.)

Figure 2.

Overview of different modes of microbiome manipulation. Antibiotics can eliminate non-target organisms in the community in addition to the intended target. Supplementation involves addition of a single or combination of beneficial cultured strains into the community (probiotics), the addition of nutrients that promote the growth of beneficial microbes (prebiotics), or the addition of microbe-produced bioactive enzymes. Transplants add in an uncultured but live microbial consortium from donor hosts to alter the existing community in the recipient, and directed therapies like phage and gene editing can be effective ways to eliminate target organisms without altering the surrounding community. (A color version of this figure is available in the online journal.)

Figure 3.

Microbial tree of life highlighting genera that have been tested as probiotics (direct-fed, enzyme production or forage additive). In total 37 microbial genera were identified from recent reviews^– and annotated on the microbial phylogenetic tree using iTOL. They are primarily comprised by bacterial groups Bacillus and Lactobacillus (LAB), but also include Bifidobacterium, Enterococcus, Lactococcus (LAB), Megasphaera, Pediococcus (LAB), Propionibacterium, and fungal groups Aspergillus, Saccharomyces, and Schizosaccharomyces (Supplemental Tables 1 and 2). Boxes represent the host group(s) for which the probiotic is used colored by host type. The color bars represent the kingdom level taxonomy over all branch tips. (A color version of this figure is available in the online journal.)