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Introduction: The overuse of antibiotics has led to a surge of antibiotic resistant bacteria in recent decades. Animal agriculture has proven to be a significant contributor to this overuse. The investigation of potential alternatives to antibiotics in animal agriculture is thus warranted. Methods: We conducted a literature review exploring four alternatives for antibiotic use in an animal agricultural setting: phytochemicals, antimicrobial peptides, probiotics, and bacteriophages. Results: Four different types of antibiotic alternatives were evaluated. The first one is phytochemicals, a broad group consisting of five subtypes: alkaloids, carotenoids, polyphenols, terpenoids, and organosulfur compounds. Many of these display antibacterial properties such as interacting with the cytoplasmic membrane, immunomodulatory activities, inhibiting specific components of DNA replication, and even inactivating specific enzymes vital for the survival of bacteria. All these subtypes displayed various antibacterial properties in animal studies surrounding poultry and livestock. The second alternative is antimicrobial peptides, which have shown to be effective in treating conditions such as post-weaning stress and necrotic enteritis in various animals. The third alternative is probiotics, which have demonstrated both growth promotion and disease prevention properties. One study also concluded that probiotics provide financial benefits to farmers. The fourth antibiotic alternative is bacteriophages, a class of viruses that infect bacteria. Phages have shown disease prevention and growth promotion properties; they also can prevent the transmission of zoonotic diseases. Discussion: Phytochemicals, antimicrobial peptides, probiotics, and bacteriophages all demonstrate the capability of acting as antibiotic alternatives. Each of these alternatives are unique with their own advantages and disadvantages; hence, the applicability is broad. Conclusion: Four antibiotic alternatives (phytochemicals, antimicrobial peptides, probiotics, and bacteriophages) were researched for disease prevention and growth promotion properties, inherent functions of antibiotics. The applicability of such options in livestock and poultry is vast. Therefore, given more funding for research studies and policy changes, many of these options can be implemented if not already.

Rationale & Objective Pathogenic variants in type IV collagen have been reported to account for a significant proportion of chronic kidney disease. Accordingly, genetic testing is increasingly used to diagnose kidney diseases, but testing also may reveal rare missense variants that are of uncertain clinical significance. To aid in interpretation, computational prediction (called in silico) programs may be used to predict whether a variant is clinically important. We evaluate the performance of in silico programs for COL4A3/A4/A5 variants. Study Design, Setting, & Participants Rare missense variants in COL4A3/A4/A5 were identified in disease cohorts, including a local focal segmental glomerulosclerosis (FSGS) cohort and publicly available disease databases, in which they are categorized as pathogenic or benign based on clinical criteria. Tests Compared & Outcomes All rare missense variants identified in the 4 disease cohorts were subjected to in silico predictions using 12 different programs. Comparisons between the predictions were compared with: (1) variant classification (pathogenic or benign) in the cohorts and (2) functional characterization in a randomly selected smaller number (17) of pathogenic or uncertain significance variants obtained from the local FSGS cohort. Results In silico predictions correctly classified 75% to 97% of pathogenic and 57% to 100% of benign COL4A3/A4/A5 variants in public disease databases. The congruency of in silico predictions was similar for variants categorized as pathogenic and benign, with the exception of benign COL4A5 variants, in which disease effects were overestimated. By contrast, in silico predictions and functional characterization classified all 9 pathogenic COL4A3/A4/A5 variants correctly that were obtained from a local FSGS cohort. However, these programs also overestimated the effects of genomic variants of uncertain significance when compared with functional characterization. Each of the 12 in silico programs used yielded similar results. Limitations Overestimation of in silico program sensitivity given that they may have been used in the categorization of variants labeled as pathogenic in disease repositories. Conclusions Our results suggest that in silico predictions are sensitive but not specific to assign COL4A3/A4/A5 variant pathogenicity, with misclassification of benign variants and variants of uncertain significance. Thus, we do not recommend in silico programs but instead recommend pursuing more objective levels of evidence suggested by medical genetics guidelines.