Researchers explore artificial sweetener and gut health link in calves

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Use of artificial sweetener as a feed additive may support gut health in young calves facing a disease challenge, says researcher.

A group of researchers explored the link between using an artificial sweetener, Sucram, glucagon-like peptide 2 (GLP-2) and gut health when calves face a disease challenge, said Erin Connor, corresponding author and researcher with the USDA-Agricultural Research Service’s (ARS) animal genomics and improvement laboratory.

“I’m interested in gut health in general, and how can we improve feed efficiency and animal well-being,” ​she told FeedNavigator.

The study sought to explore how injected GLP-2 or artificial sweetener fed to young dairy calves facing a challenge from cryptosporidiosis would alter diarrhea or the negative effects of the disease in the gut. The research group included several ARS members and Pancosma employees and the work was published in the Journal of Dairy Science​​.

The group found that the feed additive and the injected GLP-2 used before a pathogen exposure could reduce negative effects on intestinal integrity, morphology and inflammation, the researchers said.

An additional conclusion would be that there may be other opportunities to improve gut health for production animals using different feed additives that may not have been considered previously, said Connor.

“Sucram is an artificial sweetener – it’s not adding nutrition, but it’s having an effect by interacting with receptors in the gut,” ​she said. “It’s led us to other things we want to look at [concerning] how the diet can be important beyond the nutrition.”​

Why GLP2 and sweetener?​

A common cause of death, morbidity, nutrient malabsorption or reduced performance in young calves stems from diarrhea, said the researchers. One primary factor of the disease is presence of Cryptosporidium parvum​.

Treatment of diarrhea can focus on palliative care, and for cryptosporidiosis, the only drug known to work is not licensed for use in the US, they said. Options to reduce the negative effects of diarrhea could help improve animal well-being and profitability.

Past work done by researchers suggested that GLP-2 therapy could help in addressing diarrhea in calves, they said. A feed additive artificial sweetener also can stimulate an animal to release GLP-2 in the intestine.

It is possible that using the feed additive sweetener to generate GLP-2 benefits could improve calf response, intestinal health and function, the researchers said.

Previously, Connor had worked with GLP-2 to demonstrate that it could reduce some types of stress when given to calves facing coccidiosis, she said. The sweetener also had already been linked with the ability to stimulate the release of GLP-2 in the gut.

There was a potential that feeding the sweetener could be a more natural way to provide additional GLP-2 to calves, she said. “Rather than injecting animals we could feed them this artificial sweetener,” ​she added.

“We wanted to know if we could feed them ahead of time as a preventive measure, that’s how it came together,” ​she said. “They had a sweetener used in weaning pigs and it could stimulate GLP2 – we’re trying to figure out the mechanism and how all is this working.”​

Feeding trial​

In the trial, 24 calves were divided into four groups and given separate treatments for a period of 18 days, the researchers said. One group of calves was not infected but kept as the control.

The other three groups were infected with C. parvum​, one was also given 400mg/lg of dry matter of milk replacer of the commercial artificial sweetener (SUC), one group was injected with 50 ug/lg of body weight of GLP-2 twice daily (GLP2), and the remaining group was given an injection of a buffer solution, but not actually treated (INF).

All calves, save those getting the feed additive in their milk replacer, were given a commercial milk replacer, twice daily during the trial, they said. The artificial sweetener was produced by Pancosma SA, which also help fund the study.  ​ 

Calves were infected with c. parvum​ on day 8, they said.

Blood samples were collected on days 1, 8, 12, 15 and 18 and fecal samples were taken on days 1, 8, 10, 12, 14, 16 and 18, they said. Fecal scores ranging from 1 (healthy) to 5 were taken daily for each calf and diarrhea severity index (DSI) was determined.

Calves were harvested on day 18 and their digestive tracts were collected along with the epithelial mucosal layer from the jejunum and ileum, they said. Villus height was measured and the number of apoptotic cells in the ileum and jejunum were estimated along with the amount of nitrated intestinal protein in the ileal mucosa.

Results​

The control group calves remained free of cryptosporidium throughout the trial, the researchers said. Infected calves had mild diarrhea post-infection.

The DSI of the non-treated infected calves was higher than the control, but results for the GLP2 and SUC groups were lower than the INF group, they said. Fecal oocyst counts at slaughter also were lower for the GLP2 and SUC group calves.

Use of either GLP-2 or artificial sweetener before calves face a disease challenge demonstrated some protection when compared to untreated calves, they said. Treated calves saw reduced diarrhea, limited plasma indicator of inflammation, improved intestinal morphology and a drop in expression of genes working in cellular remodeling and repair.

For most variables, no major difference was found between use of GLP-2 or the artificial sweetener, they said. Neither average daily gain or the gain to feed ratio varied based on treatment.

Overall, plasma serum amyloid A (SAA) concentration was higher for the INF group compared to the control, while treated calves fell between the other two groups, said the researchers. A portion of the jejunum was heavier in INF calves compared to the control, but the SUC and GLP2 calves had increased intestinal mass to length ratios and smaller length to empty body weight ratios when compared to the INF group.

Villus height in the ileum was lower in the INF group when compared to all other groups, but only reduced in the jejunum when compared to the control group, they said. In the jejunum, the INF and SUC groups had higher levels of cells undergoing apoptosis.

In the ilium the researchers found that both the GLP2 and SUC calves had the largest amount of apoptotic cells in villi, they said.

Apoptosis is cell death, but can be used by the cell as a defense mechanism to prevent an invading organism from reproducing, said Connor. “The body will kill off the infected cell,”​ she added.

“One theory about how this organism can be so pervasive, is that it can prevent the host from going into apoptosis,”​ she said. If that is true, it appears the use of the feed additives may help return that ability to the cell, which led to the increase in apoptosis seen in infected intestinal cells.

However, the results reported also come from a single snapshot taken at the end of the study, she said. “In the future, you’d want to look at how apoptosis changes over time to get a better feel for what’s going on,” ​she added.

The estimates of positive pixels per cell and positive pixel area were lower in SUC than GLP2 but no additional alteration of protein tyrosine nitration was noted, the researchers said.