Effect of bovine respiratory disease on the respiratory microbiome: a meta-analysis.

Background: Bovine respiratory disease (BRD) is the most devastating disease affecting beef and dairy cattle producers in North America. An emerging area of interest is the respiratory microbiome's relationship with BRD. However, results regarding the effect of BRD on respiratory microbiome diversity are conflicting. Results: To examine the effect of BRD on the alpha diversity of the respiratory microbiome, a meta-analysis analyzing the relationship between the standardized mean difference (SMD) of three alpha diversity metrics (Shannon's Diversity Index (Shannon), Chao1, and Observed features (OTUs, ASVs, species, and reads) and BRD was conducted. Our multi-level model found no difference in Chao1 and Observed features SMDs between calves with BRD and controls. The Shannon SMD was significantly greater in controls compared to that in calves with BRD. Furthermore, we re-analyzed 16S amplicon sequencing data from four previously published datasets to investigate BRD's effect on individual taxa abundances. Additionally, based on Bray Curtis and Jaccard distances, health status, sampling location, and dataset were all significant sources of variation. Using a consensus approach based on RandomForest, DESeq2, and ANCOM-BC2, we identified three differentially abundant amplicon sequence variants (ASVs) within the nasal cavity, ASV5_Mycoplasma, ASV19_Corynebacterium, and ASV37_Ruminococcaceae. However, no ASVs were differentially abundant in the other sampling locations. Moreover, based on SECOM analysis, ASV37_Ruminococcaceae had a negative relationship with ASV1_Mycoplasma_hyorhinis, ASV5_Mycoplasma, and ASV4_Mannheimia. ASV19_Corynebacterium had negative relationships with ASV1_Mycoplasma_hyorhinis, ASV4_Mannheimia, ASV54_Mycoplasma, ASV7_Mycoplasma, and ASV8_Pasteurella. Conclusions: Our results confirm a relationship between bovine respiratory disease and respiratory microbiome diversity and composition, which provide additional insight into microbial community dynamics during BRD development. Furthermore, as sampling location and sample processing (dataset) can also affect results, consideration should be taken when comparing results across studies.