Testing fish feed and vaccines on mini-guts of farmed fish

Immunologists of Wageningen University & Research are growing mini-guts from the stem cells of carp, zebrafish and other farmed fish. The mini-guts are being used to develop healthy and sustainable fish feed. The researchers will also investigate whether this stem cell technology can be used to administer vaccines against infectious diseases via the feed.

Eels, catfish and yellowtail kingfish are among the fish farmed in the Netherlands. Although these fish are raised in a contained environment, they are still susceptible to infections. Sylvia Brugman and her colleagues of Next Level Animal Sciences are studying which bacteria and food components cause intestinal damage or inflammations in fish.

We expose the mini-guts of fish to food components and bacteria and observe if the intestinal wall cells respond.
Sylvia Brugman

Intestinal health in fish

“We expose the mini-guts of fish to different food components and bacteria,” explains Brugman. “We then use a microscope and gene expression techniques to observe if the intestinal wall cells respond. We also look at what happens if we switch off some genes in the intestinal wall cells using the gene editing technique CRISPR-Cas9. This is because mutations in certain genes increase the risk of inflammatory bowel disease. With this research, we are building fundamental knowledge about the processes that play a role in the maintenance of intestinal health.”

Sustainable fish feed

“Farmed fish used to be fed mostly fishmeal, but it is not sustainable to feed fish to fish,” says comparative immunologist Maria Forlenza. “To find a better form of feed for farmed fish, researchers from the Aquaculture and Fisheries group are investigating what other feed components, such as insects or plant matter, do to the intestinal wall of different fish species. The mini-guts produce mucus, just like real guts. This means we can directly measure the extent to which feed components influence mucus production and whether they damage the intestinal wall.”

We are going to administer vaccines through water and feed and see if they can penetrate the intestinal wall of the fish.
Maria Forlenza

Vaccines through water and feed

Maria Forlenza is also studying the mini-guts for another purpose: she wants to use them to screen DNA and RNA vaccines she has developed to see if they can be administered through water or feed. “Vaccinating with injections is stressful for fish. Moreover, because you have to catch all the fish first, it’s very time-consuming. We are going to administer vaccines against infectious fish diseases through the animals’ water and feed and see if the vaccines can penetrate the intestinal wall.”

An extra protective layer has been added to ensure that the vaccine capsules are not digested in the stomach. “The mini-guts are transparent, so I can use a microscope to observe directly how these vaccine capsules are absorbed,” explains Forlenza. “Using mini-guts, we require far fewer test animals for the initial screening.” Brugman adds: “We hope our research will contribute to the knowledge of farmed fish around the world and will improve the health of these animals.”