Impact of liver fluke infection on the gut-liver axis – implications for animal health

The gut microbiome mediates animal and human health via bidirectional communication with other organ systems throughout the body. The interplay between the gut and the liver, termed the gut-liver axis, mediates the progression of liver diseases in people and hepatic inflammatory disorders associated with diet in ruminants. However, the effect of parasite infections in the liver on the homeostasis of the gut-liver axis are largely unexplored in ruminants.
The liver fluke parasite, Fasciola hepatica, is an economically important parasite of sheep and cattle. It significantly impacts global livestock productivity, causing major economic losses (UK: £300 million; globally: $3 billion) and predisposition to other infectious and metabolic diseases. Liver fluke prevalence has been exacerbated by climatic conditions favourable to the parasite, and escalating resistance to several drug compounds, leading to uncontrolled liver fluke infections that represent a significant threat to animal welfare and production. The development of novel methods, such as vaccines, for the sustainable long-term control of liver fluke is of paramount importance. Critical to this goal is understanding the factors during liver fluke infection that contribute to poor animal growth and food energy conversion, and the animal parameters that can be used to assess disease severity and vaccine efficacy.
There is increasing evidence that the gut microbiome plays a key role in parasitic infections of ruminants, influencing disease progression and animal tolerance/resistance to infection. Following ingestion, F. hepatica follows a migratory path through the liver to the bile ducts, causing extensive damage leading to fibrosis and cholangitis. While the liver fluke parasite does not reside in the small intestine for long, it has the potential to impact gut-liver homeostasis that may direct disease progression and severity, and overall animal health.
This project aligns with BBSRC remit and priorities relating to sustainable agriculture, food security and animal health, and addresses key research questions related to the role of the microbiome in maintaining animal health. It aims to elucidate host-F. hepatica interactions along the gut-liver axis in sheep and determine whether gut bacteria and liver health status contribute to disease progression and animal tolerance to liver fluke infection. The interactions within the ovine gastrointestinal (GI) tract will focus on the small intestine, where bile is introduced for normal digestive processes and where the parasite begins its migratory path through the host, and the corresponding changes in the large intestine represented by faecal samples. The objectives of the project are to: (1) assess gut health during F. hepatica infection by (i) microbiome analysis, using metatranscriptomic tools to profile microbial function and diversity, and (ii) analysis of GI tract integrity by histology and molecular tools; (2) evaluate the parasite effects on hepatic and biliary homeostasis by profiling bile composition and transcriptional changes elicited by liver damage; and (3) elucidate what role F. hepatica plays in driving the effects on gut-liver homeostasis.
This project will deliver a better understanding of the role of the gut-liver axis during parasite infections in ruminants, and the host traits that promote resilience/tolerance to liver fluke infection that can be incorporated into parasite control strategies critically needed by farmers. The data will enhance our understanding of the complex nature and predisposition of F. hepatica-pathogen co-infections in ruminants that is driven by the regulation of systemic immune responses and has implications for other gut-organ axes affecting animal health.