Recently, there has been an emphasis placed on the study of the development and classification of the human microbiome, and its effects on human health. Studies have shown that the human microbiome established early in life has an effect on allergies, asthma, colitis, and type 1 diabetes, just to mention a few. It also has a major effect on the normal development of the gut immune system as well as protection of the gut from invasion by pathogens. It is also well-established that there is a gut-brain axis in humans involving a bi-directional communication system between the gut and the brain that plays a major role in the development of major depressive disorder (MDD).
It appears that research on the human microbiome is constantly revealing new information on the effects of the microbiome on health, disease incidence, and mental health. Obviously, the main goal is to learn what can be done to encourage the proper establishment and development of the microbiome as well as ways to modify or regulate it, to provide the maximum benefits to overall human health and well-being.
Likewise, there has been an increase in the research being conducted on the microbiome in other species, including ruminants. In most cases, the gastro-intestinal tract in calves is sterile before the birthing process begins. The process of colonization starts during birth as the calf passes through the vaginal canal. A wide variety of microbiota start the colonization process rapidly, starting with aerobic bacteria such as Streptococcus and Enterococcus that consume the available oxygen in the gut, helping to establish an anaerobic environment. This anaerobic environment is necessary for colonization of the first strict anaerobes in the GI tract such as Bifidobacterium and Bacteroides.
There are many factors that have a major influence on the development of the microbiota in the young calf. Some of these would be the microbiota of the dam, the environment that the calf is born into, colostrum intake of the calf, the types of feed that the calf eats, early pathogen exposure, and the use of antibiotics. The colonization of the entire GI tract, including the neonatal rumen, occurs rapidly, with anaerobic bacteria being the dominant organism in the rumen by the second day of life. The anaerobic bacterial population in the young rumen is fairly well established and stable within the first 7 days of life. Anaerobic fungi and methanogens become established around 8 to 10 days of age with the Protozoa appearing around 15 days post-partum. Even though the rumen microflora are well-established early in life, the rumen microbiome undergoes significant changes as the animal matures and establishes its adult microbiome.
It is obviously extremely important to the health of the neonate to establish a normally functional microbiota in the intestinal tract as soon as possible to help protect it against diarrheal disease early in life. The intestinal microbiota contains two basic types of organisms. One type is associated with the ingesta and resides in the intestinal lumen, and the other type is attached to the mucosa. The intestinal microbiota is important in providing protection to the calf in three different ways as explained by Dr. Chris Chase in his chapter on Enteric Immunity (Vet Clin Food Anim 34 (2018) 1-18). One is by saturation of the colonization sites on the intestinal wall which competes with pathogens for available nutrients and limits pathogen association with the host tissue. The second way is the stimulation of the production of the mucous layer on the intestinal wall along with secretory IgA and antimicrobial proteins that further decrease the ability of the pathogens to come into contact with the host mucosa. Third is that the microbiota enhances the gut immune response to invading pathogens. An in-depth discussion of these functions of the microbiota is discussed in this chapter.
The calf is approximately three weeks of age before its microbiota is established to the point where the mucin layer is well-developed and these other attributes are fully functional. This explains why we see the majority of diarrheal diseases early in life, and calves experience a lower incidence of infectious diarrhea as they get older. Management practices to improve the environmental conditions early in life are obviously very important to reduce the exposure of the newborn calf to enteric pathogens, at a point in time when they are much more susceptible.
Feeding clean, high quality colostrum as soon as possible after birth has shown a significant improvement in the bacterial colonization of the small intestine within the first 12 hours of life. If the first feeding was delayed for six to 12 hours after birth, the ability of the bacterial colonization of the normal microbiota was significantly reduced. It has also been shown that feeding colostrum early in life will enhance the colonization of Bifidobacterium, and reduce the colonization of E. coli. Therefore, colostrum also has a function in the development of the early microbiota in addition to its other functions involving passive transfer, nutrition, and epigenetic programming.
Two other very important factors in the rapid establishment of a normal microbiota are the bacterial load in the milk being fed, and the presence of antibiotics, either in the milk or administered. It has been well established that feeding unpasteurized hospital milk has an adverse effect on calf health and disease incidence. This milk contains high numbers of pathogenic bacteria since the majority of the hospital milk comes from cows with clinical mastitis. These pathogens will obviously have a direct effect on the health of the calf because of their pathogenicity, but also on the microbiota as well. As previously mentioned, the microbiota are responsible for maintaining a non-inflammatory environment in the absence of pathogens, but also to help promote the inflammatory response when a pathogen is present to try and eliminate it as soon as possible.
Any time that the normal gut microbiota is affected by stress, feed changes, bacterial challenge, antibiotics, etc., it results in “dysbiosis”. This is a change in and/or a reduction in the normal microbiota. This will result in thinning of the mucin layer, decrease in antimicrobial proteins, and other immune factors such as cytokines that are necessary for proper maintenance and function of the immune system. This will also lead to separation of the tight junctions between the epithelial cells, permitting easier access of pathogens to intestinal tissue.
Probably the most common way that dysbiosis occurs is through the use of antibiotics, especially oral antibiotics. Some people have assumed that the microbiota is resistant to antibiotics and only the pathogens will be affected by antibiotic therapy. However, this is far from the truth. Studies in humans have shown that nursing mothers taking antibiotics will have significant levels in their milk, and that antibiotic levels of less than 5 parts per billion in the milk will have an adverse effect on the microbiota of the nursing infant. It is no longer legal to put antibiotics in milk replacer, and yet it is still legal to feed hospital milk laden with antibiotics. These antibiotics will definitely have an adverse effect on the microbiota of the calf, both before and after weaning. Pasteurization will not have any effect on the neutralization of antibiotics, so it is advisable to discontinue the use of hospital milk that contains antibiotics.
Another common practice is to treat calves with diarrheal disease with oral or systemic antibiotics. The major pathogens that are involved in diarrhea in the first two weeks of life are viruses and protozoa. These organisms obviously do not respond to antibiotics, and therefore, antibiotics should not be used to treat these cases. The only exception would be if the calf has an elevated temperature, suggesting that it is developing respiratory disease, or perhaps is experiencing issues with Salmonella or toxigenic E. coli. If the diarrhea occurs between seven to 14 days, most cases will not need antibiotic therapy. It has been shown that antibiotics can be administered to healthy calves, resulting in diarrhea caused by the treatment which results in dysbiosis. Once an animal has been treated with antibiotics, it may take up to two months to repair and restore the normal microbiota. This will have an adverse effect on the subsequent health of the calf as well as its feed efficiency and growth.
The microbiota of the young calf is significantly different from the adult, and is constantly in a state of change depending on the environmental factors, feed changes, stress, disease, and antibiotic therapy. Part of a good management and nutrition program for the young calf, is providing the environmental conditions and feeding program that will minimize the effects on the maintenance of the normal microbiota. Feeding consistency, and minimizing exposure to antibiotics, unless necessary to treat bacterial disease, are important factors in promoting the establishment and maintenance of a healthy microbiota, thus maximizing the health and growth of the calf as well as future productivity.
For more of Dr. Corbett’s articles on dairy nutrition and health, see these on BovineVetOnline: