Use of Subtherapeutic Tylvalosin Against Mycoplasma hyopneumoniae: Implications For Respiratory Microbiome Dysbiosis and Swine Lung Health

Abstract

Enzootic pneumonia (EP) caused by Mycoplasma hyopneumoniae (M. hyopneumoniae) has a significant impact on swine production. Subtherapeutic exposures of tylvalosin in swine, often due to inconsistent dosing in feed or water, promote antimicrobial resistance. This study investigated the efficacy of 1.0625 mg/kg/day of tylvalosin administered for 7 days via feed to pigs experimentally infected with the UFV01 strain of M. hyopneumoniae and its impact on the respiratory microbiome. Thirty landrace x large white female piglets were divided into three groups: G1 (negative control, n = 2), G2 (infected, n = 14) and G3 (infected and treated, n = 14). Clinical signs, seroconversion, macroscopic and microscopic lung lesions and bacterial load were assessed. The respiratory microbiota of swine was analysed through 16S rRNA gene sequencing, followed by bioinformatics analyses. While G1 piglets remained healthy, G2 and G3 piglets developed lung lesions consistent with EP, although no significant difference was observed between these groups. Seroconversion was higher in G2 (90.9%) than in G3 (45.5%) at 35 days post-infection, suggesting modulation of the humoral immune response by tylvalosin. Microbiota analyses revealed a significant shift in post-infection composition, with infected pigs exhibiting reduced alpha diversity and distinct beta diversity compared to healthy pigs. M. hyopneumoniae dominated the respiratory microbiome of infected animals, drastically reducing the abundance of other taxa, notably Stenotrophomonas maltophilia. While tylvalosin treatment partially restored alpha diversity and shifted the microbiota composition towards the control group, it failed to eliminate M. hyopneumoniae. Variivorax, Ralstonia and Pseudomonas were identified as potential biomarkers for respiratory health and treatment response. These findings emphasise the complex relationship between M. hyopneumoniae infection, suboptimal tylvalosin dosage and resulting respiratory microbiome dysbiosis. Identifying and correcting the inappropriate use of antimicrobial dosages in clinical and preventive treatments, as well as promoting research focused on optimising dosage strategies and management practices, is essential for swine production and for reducing antimicrobial resistance. Moreover, maintaining a balanced microbiota may be a key factor in achieving healthier swine production, both in terms of animal welfare and food safety for consumers.