Why does farming carnivores increase the risk of ‘disease reservoirs’?

• Researchers recently investigated why carnivorous mammals carry so many infectious diseases that affect both animals and humans.
• They found that carnivores have either missing or mutated immune genes that make them less able to identify and fend off pathogens.
• Scientists believe that the antimicrobial effects of a carnivorous diet help compensate for carnivores’ impaired immunity.
• The researchers say farming carnivores in proximity could increase the risk of “disease reservoirs” forming.

Many viral and bacterial pathogens, including SARS-CoV-2 and Salmonella, can infect animal hosts before causing infection in humans.

Around 49% of all carnivore species, including mink and dogs, carry one or more zoonotic pathogens — infectious diseases that jump from animals to humans. This is more than any other mammal, including bats.

Why exactly carnivores carry so many zoonotic pathogens is unknown. Researchers have speculated it may be due to differences in their immune system or that, as they naturally carry many pathogens, they proportionally carry more zoonotic pathogens.

Understanding how zoonotic pathogens behave in carnivores could help researchers protect against their risks to human health.

In a recent study led by the University of Cambridge in the United Kingdom and Genentech Inc. in South San Francisco, researchers found carnivorous animals lack key genes needed to detect and protect against pathogens.

“We’ve found that a whole cohort of inflammatory genes is missing in carnivores — we didn’t expect this at all,” says Prof. Clare Bryant in the University of Cambridge’s Department of Veterinary Medicine and senior author of the paper.

“We think that the lack of these functioning genes contributes to the ability of pathogens to hide undetected in carnivores, to potentially mutate and be transmitted, becoming a human health risk,” she added.

The study appears in Cell Reports.

Immune response

To begin, the researchers examined carnivore genomes on the Ensembl genome database for the presence of genes related to the immune system and cell death. They discovered carnivores have different genes linked to immunity than humans and mice.

To see how these genes worked in practice, the researchers conducted experiments on immortalized cell lines made from dog immune cells. They tested the inflammatory response of these cells to bacteria, including S. Typhimurium, a leading cause of human gastroenteritis.

In doing so, they found that dog cells had a remarkably compromised response compared to human cells.

To understand why this was the case, the researchers performed a genetic analysis of the cell lines. They found that key infection detection genes were missing from carnivorous animals, such as dogs.

While three genes needed for gut health were present in dog DNA, they had lost their function. The researchers also found a third gene important for gut health developed a mutation that caused two enzymes called caspases to fuse. This fusing renders it unable to play its vital role in processing proinflammatory immune response.

‘We found that animals in the order Carnivora had either lost receptors (triggers) that recognize bugs or acquired an effector caspase protein (one that processes inflammatory proteins to their active form) that was mutated, leading to inefficient recognition of bugs and markedly reduced immune responses against them,” Prof. Bryant told Medical News Today.

When encountering pathogens in the gut, human and mouse immune systems activate inflammatory cell death pathways that protect the gut against infection. As the genes needed for these processes either do not exist or do not function in carnivores, they are unable to recognize some pathogens and poorly respond to others.

“While [the missing genes compromise] the inflammatory response of dog cells against pathogenic microbes, this is more important in the gut than anywhere else, and we think the carnivores, because of the antimicrobial nature of their high protein diet, have lost the need for these immune genes in the gut,” Prof. Byrant told MNT.

“This is a problem in other organs, too, for example, the lungs, and so this could help explain the problems seen with mink and COVID-19.”

Evolutionary adaptation 

To explain their results, the researchers say that carnivores’ high protein diets have antimicrobial properties. Therefore, they speculate that the loss of functionality among specific immune genes in carnivores could be due to protection from their dietary habits.

The team suggests the evidence for this is that carnivores expel gut infections as diarrhea — one of the 21 most common reasons people take pets to a vet. Moreover, both cats and dogs can asymptomatically carry Salmonella.

“The loss of immune genes, particularly the mutation of the effector caspase, occurred early in the evolutionary tree — all of the carnivores have this mutant protein,” said Prof. Byrant, “This suggested to us something fundamental about the carnivore lifestyle that could have led to these genes not being required and therefore to their loss over a very long time.”

“Elegant work in maggots fed on a high protein diet shows that eating this type of food reduces the amount of microbes in their guts [markedly], and we hypothesize that this is what has happened in the Carnivora. A high protein diet produces antimicrobial substances, lowering the presence of pathogens in their guts so reducing the need for these immune genes to fight infections there,” she explained.

“It also means, however, that these immune genes are also lost or mutated elsewhere in the body.”

To conclude, the missing genes in carnivores could impair their immune systems’ ability to sense pathogens and therefore leave them undetected and at risk of accumulating and mutating.

However, the researchers say their results do not mean cats or dogs can transmit SARS-CoV-2. Rather, they say that large numbers of carnivores kept close together could create a “disease reservoir” that allows pathogens to mutate.

“If you remember, mink got infected with SARS-CoV-2, and the virus was thought to have mutated in them and spread back to people,” said Prof. Byrant. “So, similar to a school environment or other places where lots of people are clustered together indoors increases the amount of virus and the potential for mutation, farming the mink results in large numbers of animals being clustered together, which facilitated what happened.”

“In contrast, similar to the school holidays, this type of event does not seem to happen when animals are dispersed in small numbers, as this problem really has been restricted to the mink farms during the pandemic,” she concluded.

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