Modifying the Intestinal Microbiota in Animals

One way to change the microbiota is microbiome transplantation, or transferring the intestinal contents from an animal with a healthy gut to an animal with dysbiosis. The variability of the donor microbiota and the potential presence of pathogens are, however, causes for concern. It is more desirable to identify and characterize the specific bacteria that can constrain the growth of unwanted organisms.

It is believed that fecal transplants act to restore the normal microbiota and increase their diversity. 

In animals, the most common and longest established form of such a transplant is the use of fresh ruminal contents to restore ruminal function in cattle that have had a ruminal impaction or other event that has destroyed the ruminal microbiota. In these cases, it is unclear whether the beneficial results are due to the bacteria; the many other organisms, such as protozoa and viruses; or the provision of bile acids, vitamins, or proteins.

Fecal transplants have proven successful in treating C difficile infections in humans.

Another widely used technique is to deliver a mixture of organisms that outcompete selected intestinal pathogens such as Salmonella. This involves oral administration of diluted feces or complex bacterial mixtures to poultry and pigs. 

Competitive exclusion techniques have been used in the poultry industry for many years in an effort to minimize S enteritidis infection in birds. In initial studies it was found that the normal microbiota of adult birds could prevent Salmonella colonization in chicks. 

The effect was ascribed to the obligate anaerobic bacteria that can be grown in a mixed culture. Thus, adult-type resistance to Salmonella could be established by administering adult microorganisms. This is called the Nurmi or competitive exclusion technique.

It is believed that the effect is mediated by competition for nutrients and attachment sites as well as the production of antibacterial substances. The observation that an established Salmonella serovar in a bird’s intestine can prevent subsequent colonization by other Salmonella serovars reflects a similar phenomenon.

Prebiotics are compounds that affect the composition or activity of the gut microbiota. Examples include wheat starch, beet pulp, inulin, nonstarch polysaccharides, fructo-oligosaccharides, and galacto-oligosaccharides. 

The same principle is involved in the feeding of high-fiber diets. These provide bulk and, when metabolized by the microbiota, generate large amounts of immunostimulatory short-chain fatty acids. They also induce anti-inflammatory cells, such as regulatory T cells. 

Prebiotics also serve to protect the gut epithelium and increase mucus production. They may increase numbers of lactobacilli and bifidobacteria in dogs and cats while decreasing the numbers of potential pathogens such as Escherichia coli and Clostridium perfringens.

The nutritional composition of feed is known to influence the composition of the microbiota as well as their metabolic products. 

Probiotics are cultures of living bacteria that, when fed in sufficient amounts, may improve host health. Probiotics are widely used in humans because the underlying rationale for their use is clear. They are also generally regarded as safe.

It has been suggested that probiotics decrease intestinal permeability, increase mucin production, increase production of defensins, generate short-chain fatty acids, stimulate IgA production, alter intestinal pH, and possibly even act as immunostimulants. Unfortunately, there are few scientific data to substantiate many of these claims. 

Feeding probiotics is designed to provide large numbers of a single bacterium or a mixture of bacteria, in anticipation that these will colonize the intestine and improve or restore the microbiota in some manner. There are two major problems with this approach. 

First, the probiotic must contain sufficient living bacteria to cause a substantial change, and second, the duration of any induced changes is totally unknown. The intestinal microbiota are generally stable and resistant to major changes in their composition. Even if temporarily altered, they will often revert to an original state. 

Lactobacilli and Bifidobacteria are commonly used in commercial probiotics and appear to decrease susceptibility to diarrhea and respiratory tract infections. Others may also contain Bacilli and Streptococci. 

The effects of probiotics depend not only on the dose but also the precise strain and composition of the mixture fed. If these organisms are to be delivered to the intestine, they must also survive exposure to the stomach and bile acids. Although the probiotics may not survive long, some consider that transient colonization may be beneficial.

Several probiotic mixtures have been shown to benefit mice and humans, especially in decreasing bacterial diarrhea.

Research on probiotics is ongoing in dogs. An example is the use of cultures of lactobacilli to lower intestinal pH and thus decrease coliform populations. Ideally, this will also decrease inflammation and inflammatory cytokine levels. Lactobacilli are, however, only a small component of the canine microbiota. 

Some probiotics may decrease the severity of allergic diseases. For example, it is possible that some lactobacilli, such as Lactobacillus rhamnosus, may alter the Th1/Th2 balance in an animal and thus decrease the severity of canine atopic dermatitis by decreasing specific IgE production.

Encouraging results have also been obtained in using probiotics to treat inflammatory bowel disease, protein-losing enteropathy, and chronic diarrhea. In general, however, improving animal health by modifying the gut microbiota is probably best effected by longterm dietary changes.

Huge quantities of antibiotics are incorporated in livestock feed, where they act as growth promoters. It is claimed that they decrease pathogen load, subclinical disease, and growth-inhibiting metabolites (eg, NH₃); they may also decrease competition for nutrients and decrease inflammation, making more energy available. Their use, however, is controversial because of their potential to transfer antibiotic resistance to human pathogens as well as their ability to cause dysbiosis.