The Intestinal Microbiota
In different animal species, the intestinal microbiome is undergoing continuous scrutinized evaluations. Some scientific groups have even referred to it as the hidden metabolic organ. This statement may not be too far-fetched, as we know that the microbiome, which contains over 100 trillion microbial cells (with ca. 1000 different bacterial species), can have a physiology and pathology of its own, where the individual health can be damaged when its combined population organization is affected. Additionally, the intestinal microbiome is known to have a strong influence in the physiology, metabolism, nutrition and immune function of the animals, where any changes (to this bacterial population) can have major consequences, both beneficial and detrimental, for their health. Undoubtedly, the majority of microbes living within the animals are not pathogenic; it is the negative alteration of this balanced intestinal microbial ecosystem, known as «dysbiosis» or «dysbacteriosis» that can result in different disease conditions. When talking about animal production, it is not surprising that animals with a more diverse microbiota have better chances of a healthier life and even better chances to grow to their full potential being more resistant to diseases. A study that compared germ-free animals, or animals that do not require the presence of microbes to survive, to those that do, concluded that the germ-free animals were much more susceptible to infection. Thus, it is proposed that the healthy bacteria that inhabit the gastrointestinal tract promote good health by neutralizing the adverse activities of harmful commensals and invading microbes. However, there are many factors that can disturb the intestinal bacterial balance. Some are external factors, such as stress, current physiology of the animal, nature and quality of feed and its raw ingredients, characteristics of the microbiota itself, the use of antibiotics and the symbiosis or competition among all these factors. Antimicrobial agents, such as antibiotics, are known to affect the microbial community balance, thus having an impact on the animal’s physiology and growth. There are a growing number of studies investigating antibiotics use and their effects on intestinal microbiota biodiversity changes.
In animal production the introduction of antibiotics was one of the most significant achievements of the 20th century for the feed industry. Because of their success as growth promoters, and because of their «miraculous» therapeutic effect on most infections, there was an excessive approach towards prescribing them; and their potential to develop resistance was, has been, and continuous to be (in many countries) overlooked.
Antimicrobial resistance is multifactorial and one of the many factors has been animal production. It is known that exposure to antibiotics and other antimicrobial products, in animals or in the environment, applies selective pressure that encourages resistance to develop favouring both «naturally resistant» strains and strains which have acquired resistance. It is recognized that the application of antibiotics to animals, via feed and/or via water, pose a risk of developing increased resistance and virulence in pathogenic bacteria. This could establish a population of infectious bacterial pathogens with antibiotic resistance that would transfer from animal to animal or animal to human via the food chain or by direct contact in both animals and humans. Most organisms can be sources of resistance genes, but selection for antibiotic resistance most often takes place in non-pathogenic microorganisms. Since non-pathogenic microorganisms comprise the vast majority of the microbial world, antibiotic resistance genes can be and are easily transmitted from animal to human gastrointestinal microflora, affecting future treatments of diseased animals within a farm and potentially having a negative impact on the food chain.
According to the Food Policy Research unit at the University of Bradford (UK), the major reasons for consumers eating less meat have been due to concerns of the feeding of antibiotics and of animal welfare, while in the minority of cases it has been due to cost.
Even though the use of antibiotics in farm animals may be a very small contributing factor to the increase in MDR bacteria, prophylactic treatments on farms can provide favorable conditions for selection, spread and persistence of antibiotic resistant bacteria. Consumers’ concerns need to be addressed, and thus the poultry industry should become proactive in the search for different innovative and effective solutions. There is also an increased interest from governmental agencies and retailers to reduce or eliminate the use of antibiotics, which creates a challenge to the livestock and poultry industry. Studies show that when reducing the antibiotic use in a specific area, the prevalence of resistant bacteria to such antibiotic is also reduced. This gives hope to search for alternatives to reduce the use of antibiotics to maintain animal health, improve performance in today’s rearing conditions, and address consumer concerns while being conscious of the global impact this may have if nothing is done about it.
Antibiotics: beyond resistance
The intestinal microbiota is crucial for maintaining immune homeostasis in the gut mucosa and thus it is essential in modulating the intestinal immune responses during both health and disease.
The antimicrobial agents not only affect the pathogens to which they are directed, but may also impact other members of the intestinal microbiota. Additionally, the microbiome responds in different ways to different antibiotics and while some antibiotics do not induce too many intestinal environmental disturbances, others have a drastic negative influence in the diversity and prevalence of many different bacterial species. The ratio between diverse bacterial species is very important to obtain optimal physiology and nutrition. Any changes in the diversity and type of bacteria create changes in oxygen and nutrient availability, creating dysbiosis. The extent of the impact depends on the particular antibiotic used, its mode of action and the degree of resistance in the community, sometimes an imbalance in the gut microbiota due to antibiotic administration can result in antibiotic-associated diarrhea. Interestingly, the microbiome has been proven to have essential functions beyond the digestive system. Studies have revealed that the microbiota can regulate immune responses in the respiratory mucosa. For example, in humans, oral neomycin treatments, which mainly target intestinal bacteria, have been shown to eradicate the immune response to respiratory influenza infection. Other studies showed that oral ampicillin treatments had a systemic effect on eliminating most of the Gram-positive bacteria, with an overgrowth of Enterobacter spp. in both the colonic and nasal mucosa. A systematic metagenomic analysis of total microbiota communities affected by similar oral antibiotic treatments revealed that intestinal mucosa-associated Lactobacillus spp. are significantly reduced. Furthermore, research using B-lactam antibiotic treatments (such as penicillin, cephalosporin, and amoxicillin), have also shown that different metabolic functions such as sugar metabolism, synthesis and degradation of intestinal and colonic epithelium, can be affected. While these data are from studies in humans, there are data that support inferences made from human microbiome data to the poultry microbiome.
In turkeys and other poultry species the microbial population starts to stabilize around 14 days of age, but the community composition continues to change with a period of stabilization between feed changes and rapid skeletal growth followed by further changes during grow-out. If microbial communities are stable, all physical and physiological places should be filled, but if microbial communities are immature or in transition, the possibility remains for opportunistic colonization by pathogens. If poults or chicks are given antibiotics at any stage, most probably the effect on the microbiome will cause more negative effects than positive. Currently, it is believed that after antibiotic therapy, the intestinal microbiota stabilizes after a few weeks. However, when researchers have analyzed the bacterial flora in more detail, they found that a short-term antibiotic exposure (7 days) can have persistent long term impacts on the intestinal microbiota that remain for up to 2 years post-treatment.
Because antibiotic use is prevalent in the treatment of different infections during animal production, there is a possible harmful effect of such treatment in initiating proper immune responses to the disease. Since the microbiome can be modulated via feeding, dietary intervention could modulate this intestinal microbiome to enhance feed conversion, gut health and immunity. The differences in genetics, anatomical features of the intestinal tract and physiology, as well as the type of feed that the animals consume, will have an effect on bacterial diversity between different animal species. Thus the determination of whether probiotic therapy can be explored for immune-stimulating effects and disease control in different animal species should continue to be evaluated.
It is evident that part of the AGP mode of action was based on the effect against gram positive bacteria, reducing the energy requirements of the intestine. Beneficial effects were observed upon gastrointestinal health, particularly in mitigating necrotic enteritis, which is associated with an overgrowth of Clostridium perfringens. Despite the benefits that had been observed when using AGP for the improvement of animal performance, AGP created an imbalance in the intestinal microbiota. This was caused by eliminating all gram positive bacteria (pathogenic and beneficial), resulting in an overgrowth of gram negative bacteria. An ideal replacement for AGP are products that can eliminate pathogenic gram positive bacteria only, maintaining the rest of the microbiome unharmed, resulting in the least disturbance of the intestinal microbial environment.
In the absence of AGP, intestinal health management for optimal performance can be accomplished with the use of active microbials. Not all active microbial strains are equally efficient due to differences in survival and persistence in the harsh conditions of the gastrointestinal tract, mechanism of action, and to differences in immunomodulatory performance. Some active microbial strains are able to inhibit Clostridium spp., but the mechanism of action by which this objective is accomplished varies. Some can secrete specific molecules, which stimulate the growth of beneficial bacteria in the micro flora, such as Lactobacillus spp. and Bifidobacterium spp. This gives a balanced ratio between these and Clostridium spp. resulting in healthy and productive animals. Others can also have an effect on the inflammatory status of the intestinal tract of the animals. Bacillus subtilis strain, PB6, (ATCC- PTA-6737), is an active microbial that has proven, in in vivo and in vitro assays, to be highly effective in its capacity to inhibit growth of different pathogenic strains of Clostridium spp. and to have anti-inflammatory effects. PB6 in vivo has also been able to show that it can help balance the first-line mediators of inflammation. Very few active microbials have been able to prove the in vivo and in vitro effects.
By maintaining a state of balance in the gastrointestinal tract, Bacillus subtilis PB6 improves the growth rate and feed utilization of poultry and other livestock. Bacillus subtilis PB6 is unique in that it has the ability to inhibit different strains of Clostridium, while the populations of beneficial bacteria such as Lactobacillus spp. and Bifidobacterium spp. are maintained. Turkeys have shown improved weight gain, feed conversion rates, mortalities, and rejections or condemnations at slaughter house compared to a negative control or antibiotic treatments.
The intestinal tract has two main functions: the digestion and absorption of nutrients, and a fundamental barrier to the external environment, protecting against infection and disease.Trillions of bacteria, known as the gut microbiota, help to keep the intestinal environment in balance. Recent research on bacteria-host interactions has provided new insights into the role of intestinal bacteria in several physiological processes, which vary from epithelial barrier development to immune properties. In a healthy state, bacteria supply nutrients and energy to the animals via the fermentation of non-digestible dietary components in the large intestine; they can also influence the efficiency of nutrient utilization by competition, deconjugation of bile salts, and stimulation of immune responses which divert nutrients for growth to tissue response and antibody production. On the other hand, there are pathogenic bacteria that can act as sources of inflammation and infection, being involved in gastrointestinal diseases, and important contributions to losses in growth and other performance parameters. Interestingly, the diet has a great influence on the composition and diversity of the intestinal microbiota; there are new possibilities for health manipulation of the animals via the diet. In recent years the use of probiotics, butyrates, plant extracts and organic acids in animal production have been increasing in popularity for both the prevention and treatment of a variety of diseases; especially because one of the main challenges for animal farming in Europe and around the world is the pressure of raising healthy animals under optimal welfare standards and using smaller amounts of antibiotics. Antibiotics certainly will need to continue to have a place in a sustainable poultry production, in order to control disease outbreaks and maintain animal welfare. However, if the pressure continues and the controlled low usage of antibiotics becomes mandatory in different parts of the world, a strong focus on nutrition-based health will be necessary in order to compensate for the absence of antimicrobials. It will be of utmost importance to realize that whatever is offered to the animals via feed or water will have an impact on the intestinal microbiota and thus in the animal’s health and performance. Feeds will need to be low in compounds, which generate an inflammatory response. The digestive stress from feed ingredients should be alleviated with enzymes and immune-stimulatory molecules like butyrates.
Gastrointestinal health should be improved with the use of organic acids, SCFA, and probiotics, particularly those effective against C. perfringens to control necrotic enteritis or dysbacteriosis.
In summary, feeding the gut microbiota will become a vital component of feed formulation and animal production and should be taken into account in the near future.