Diving Deep Into Liver Abscesses

Background 

Liver abscesses (LA) are common and costly issues in feedlot cattle. They reduce animal performance and lead to economic losses. In most cases, they are found as lesions at slaughter with no clear clinical signs that the live animal was affected.

The most widely accepted theory of how liver abscesses develop is that rumen acidosis caused by high-grain finishing diets can damage the rumen lining, allowing gut bacteria to enter the bloodstream and establish in the liver. Once established, these bacteria cause an abscess or multiple abscesses, which are localized infections. While this theory is widely accepted, the reasons why liver abscesses develop in some animals but not others remain poorly understood.

Bacteria such as Fusobacterium necrophorum and Trueperella pyogenes are commonly found in liver abscesses. There is evidence that other bacterial species are also involved. Therefore, it is still not understood how these bacteria “invade” the liver and “help” one another form an abscess, nor when the LA forms during the feeding period or to what extent the liver’s functions are compromised by abscesses.

Liver abscess prevention in feedlot cattle is currently managed with in-feed antibiotics such as tylosin, virginiamycin, or chlortetracycline. All three of these ingredients now require a veterinary prescription for use due to stricter regulations on antimicrobial use.

A better understanding of liver abscess formation could lead to the development of alternative prevention strategies to reduce the risks.

Objectives

• Apply meta-omics approaches to determine whether the microbial community of liver abscesses differs across animals.
• Use host transcriptomics to examine how animal gene expression in the liver is impacted by abscess formation and identify factors predisposing animals to the development of liver abscesses.
• Apply microbial genomics to examine the relationship between microbes in the rumen and those found in animals with and without LA.
• Determine how liver gene expression changes during the finishing period and whether those changes are associated with LA formation.
• Identify targets for future vaccine or therapeutic development.
• Examine alternative feeding strategies that can reduce antimicrobial use while still effectively preventing liver abscesses.

What they Did 

This project used a comprehensive, multidisciplinary approach to better understand LA in feedlot cattle. Researchers collected samples from other ongoing feedlot studies that assessed different diets. These samples were blood, rumen fluid and liver biopsies taken during the feeding period and at slaughter. This allowed them to track changes in the animal and its microbiome (communities of microbes) over time and to link these changes to the presence of LA at slaughter.

The research team used DNA sequencing to characterize the microbial communities in the rumen in cattle that had and did not have LA at slaughter. This allowed them to identify which bacteria were present in which samples and whether these bacteria were “active,” as well as to hypothesize whether the same bacteria found in the rumen were the ones found in the abscesses. They also compared abscesses of different severity to determine whether the microbes were the same.

In parallel, the team examined gene expression in the liver and blood of animals found to have liver abscesses. This allowed them to gain a more thorough understanding of the biological pathways likely altered by abscess development and to determine whether these changes could be used to detect LA before slaughter. Finally, the researchers integrated microbiome, gene expression and animal performance data to better understand how diet, rumen function, microbial activity and host responses interact in the development of liver abscesses.

What They Learned

This team discovered a new bacterium, Bacteroidetes purulensis, involved in liver abscesses, which had not been previously described. Besides this, they demonstrated that liver abscesses are not caused by a single bacterium, but instead involves complex interactions among multiple microbes that can influence the development of LA.

Overall, Fusobacterium necrophorum was the most frequently detected bacterium in LA and was usually found alongside other bacteria, such as Bacteroides, which appear to play an important role in abscess development. These bacteria can break down tissue, consume energy available in animal cells and evade the animal’s immune system. Given this, liver abscesses could be considered a polymicrobial condition involving multiple organisms. Interestingly, many of the bacteria associated with liver abscesses can be detected in both animals with and without them, making this a difficult problem to solve.

Additionally, the team described two types of abscesses: those predominantly dominated by Fusobacterium and those dominated by both Fusobacterium and Bacteroides.

Factors such as diet, rumen health and the animal’s immune response also influence whether an animal develops LA. Abscessed areas were found to be inflamed, and the liver structure had been disrupted by the abscesses. This affected the liver’s ability to perform its functions properly in that area (e.g., detoxification). However, the surrounding unaffected tissue did not appear to be affected in the same way.

They also found that the bacteria found in the rumen don’t predict whether an animal is likely to develop LA. Additionally, based on their results on host gene expression, it is very likely that LA forms towards the end of the feeding period.

Regarding the impact of nutrition on liver abscesses, the researchers collaborated on several ongoing feedlot studies, and the findings have been published elsewhere.

Overall, these results show that liver abscesses arise from interactions among diet, microbes and the animal’s response, rather than from a single cause, and that they develop in the latter half of the feeding period.

What It Means

This systems-level approach advanced understanding of the biological processes driving liver abscess formation and revealed new avenues for improved disease management, diagnostics and prevention. These results show that liver abscesses are complex conditions driven by interactions between diet, rumen microbes and the animal’s own response, rather than by a single pathogen or a simple genetic trait. This means that relying on one approach, such as antibiotics alone, is unlikely to fully control the problem. Instead, more effective strategies will likely involve a combination of improved feeding and management practices and new tools that target the multiple bacteria involved in abscess formation.

The ability to detect blood changes associated with the development of liver abscesses also provides an opportunity to identify at-risk animals before slaughter. While this would be logistically challenging in a feedyard, there may be an opportunity to target interventions more effectively and specifically.

There may be an opportunity to reduce the use of prophylactic antimicrobials early in the feeding period, as it appears that liver abscesses are more likely to develop during the latter portion of the feeding period.