Unexpected finding of Fusobacterium varium as the dominant Fusobacterium species in cattle rumen: potential implications for liver abscess etiology and interventions

Lay Summary The conventional method of liver abscess prevention in feedlot cattle is in-feed use of tylosin to target Fusobacterium necrophorum, which has been presumed to be the most common Fusobacterium species within the ruminal compartment. Our investigation into ruminal Fusobacterium, however, revealed a different species, Fusobacterium varium, to be abundant and ubiquitous in ruminal content samples. Furthermore, growth conditions tailored to enrich F. necrophorum consistently promoted growth of F. varium, and the bovine isolates tested had much lower susceptibilities to the commonly fed antibiotics tylosin and monensin compared to F. necrophorum. Fusobacterium varium is an emerging pathogen in humans and preliminary genome sequencing of two ruminal F. varium isolates revealed genes linked to pathogenicity. While the ecological role of F. varium in the rumen is still not fully understood, our findings draw attention to this pathogen and its potential implication in liver abscesses. The use of in-feed tylosin to control cattle liver abscesses hinges on the dogma that Fusobacterium necrophorum in the rumen is the main etiologic agent. The unexpected finding of higher abundance of F. varium, a known human pathogen, in rumen fluid samples from cattle and its' resistance to tylosin and monensin calls for greater attention to its role in liver abscess etiology and mitigating interventions. Fusobacterium varium has been generally overlooked in cattle rumen microbiome studies relative to the presumably more abundant liver abscess-causing Fusobacterium necrophorum. However, F. varium was found to be more abundant in the rumen fluid of cattle and under culture conditions tailored to enrich F. necrophorum. Using near-full length 16S ribosomal ribonucleic acid sequencing, we demonstrate that F. varium grows under restrictive conditions commonly used to enumerate F. necrophorum, suggesting that previous F. necrophorum abundance assessment may have been inaccurate and that F. varium may be an underestimated member of the ruminal bacterial community. Fusobacterium varium were not as susceptible as F. necrophorum to in-feed antibiotics conventionally used in feedlots. Exposure to tylosin, the current gold standard for liver abscess reduction strategies in cattle, consistently hindered growth of the F. necrophorum strains tested by over 67% (P < 0.05) relative to the unexposed control. In contrast, F. varium strains were totally or highly resistant (0%-13% reduction in maximum yield, P < 0.05). Monensin, an ionophore antibiotic, had greater inhibitory activity against F. necrophorum than F. varium. Finally, preliminary genomic analysis of two F. varium isolates from the rumen revealed the presence of virulence genes related to those of pathogenic human F. varium isolates associated with active invasion of mammalian cells. The data presented here encourage further investigation into the ecological role of F. varium within the bovine rumen and potential role in liver abscess development, and proactive interventions.

Automated summary

The commonly used method to prevent liver abscess in feedlot cattle is in-feed use of tylosin, but our investigation revealed that Fusobacterium varium, a different species from Fusobacterium necrophorum, is abundant in the ruminal compartment. F. varium, which is an emerging pathogen in humans, showed resistance to commonly fed antibiotics and had genes linked to pathogenicity. This finding suggests that F. varium may play a more significant role in liver abscesses than previously thought and calls for further research and interventions.