Multidimensional Phenotypic and Microbiome Studies Uncover an Association Between Reduced Feed Efficiency in Sheep During Mycoplasmal Pneumonia and Microbial Crosstalk Within the Rumen-Lung Axis.

Mycoplasmal pneumonia of sheep (MPS), caused by , profoundly impacts ovine productivity and survival. Although gut-lung microbiota interactions are increasingly recognized in respiratory diseases, whether similar crosstalk occurs between the lung and rumen microbiota in MPS-affected sheep remains unknown. To investigate alterations in the lung and rumen microbiota of sheep with MPS, the crosstalk between these microbial communities, and their impacts on growth phenotypes. From a cohort of 414 naturally infected six-month-old male Hu sheep, we selected 10 individuals with severe pulmonary pathology and 10 healthy controls for detailed phenotypic and microbiome analyses. Assessment of 359 phenotypic traits revealed that MPS significantly impairs feed efficiency and growth rate ( < 0.05). Through 16S rRNA gene sequencing, we found that MPS significantly altered the pulmonary microbiota community structure ( < 0.01), with a noticeable impact on the rumen microbiota composition ( = 0.059). was significantly depleted in both the rumen and lungs of diseased sheep ( < 0.05) and strongly associated with reduced average daily feed intake ( < 0.05). In addition, pulmonary and ruminal were significantly enriched in MPS-affected sheep, showed a strong positive correlation ( < 0.05), and were both negatively associated with feed efficiency ( < 0.05). Notably, subsp. may act as a keystone species influencing feed efficiency. These findings point to a previously unrecognized rumen-lung microbial axis that may modulate host productivity in sheep affected by MPS. This work provides new insights into the pathogenesis of MPS and offers potential targets for therapeutic intervention and management.