Table 1.
Current and prospective alternatives to antibiotics based on an ecoimmunological view.
| Groups | Examples* | Pros | Cons |
|---|---|---|---|
| Environmental prevention, husbandry and management techniques | Controlled therapeutic and particularly nontherapeutic antibiotic use in animal agriculture; all-in/all-out production; hygiene; drinking water quality control; measures to decompose or remove residual antibiotics from animal food, water and waste | Most effective and preventive measures in the long term | Requires global collaboration, huge investment, and some measures are not feasible in developing countries/areas |
| Pathogenic bacteria | Bacteriophages and endolysins; predatory bacteria; metals and minerals; bacterial virulence inhibitors; bacteriocins and antimicrobial peptides; pathogen-targeting aptamers; AR genes editing with CRISPR/Cas9 system; measures to eradicate persisters | Pathogen-targeting to obtain control of epidemic infectious bacteria | All pathogen-killing measures have potential for directional selection of pathogenic resistance |
| Microbial ecology | Bacterial growth inhibitors, or bacteriostatic metabolites; prebiotics/probiotics; fecal commensal transplantation; bacteriocins and antimicrobial peptides; quorum sensing inhibitors; biofilm inhibitors; c-di-GMP and c-di-AMP | Good for establishing inter-regulatory microbial system via community compulsion or ecological signaling | Most are based on black-box trials, there is a lack of mechanistic studies and effective measures to regulate pathogens over time |
| Animal immunity | Late weaning, colostrum quality and intake; egg yolk immunoglobins; antimicrobial peptides; preventive vaccines or adjuvants; innate immune signaling molecules; regulation on immunity seasonality | Host immunity-centered on promoting animal health in general or disease-targeting, to avoid AR development | Cost and challenges for developing cross-protective vaccines and immunological measures |
| Animal metabolism, physiology and inter-systemic interaction | Metals and minerals; essential oils; amino acids; nucleotides (including c-di-GMP, c-di-AMP, and cGAMP); enzymes; bioactive food additives including plant, and yeast extracts; innate immune signaling molecules; short-chain fatty acids; FDA-approved drugs working on G-protein coupled receptors and calcium signaling | Synergistic promotion of both animal growth and health, less chance to develop AR | Less effective during disease epidemics or pandemics |
| Host-pathogen interaction | Quorum sensing inhibitors; Compounds that inhibit bacterial adhesion; c-di-GMP, c-di-AMP, and cGAMP; aptamers or other inhibitors to intervene in host-pathogen interaction | A non-killing measure to effectively suppress on-site infections and less chance to develop AR | Requires identification of key components mediating pathogen-host interaction, more suitable for viral diseases |
*Format legends: Italic, have multiple action models, such as both bactericidal and animal regulation roles of metals and minerals; Bold, most recently studied or prospective alternatives to antibiotics germane to an ecoimmunological view. Abbreviation: AR, antibiotic resistance; c-di-AMP/GMP: cyclic diadenylate/diguanylate monophosphate; CRISPR, bacterial clustered regularly interspaced short palindromic repeats (CRISPR); Cas9 CRISPR-associated protein 9 nuclease. See Section 3 and 4 for details and related references.