Antibiotics have been used for more than 60 years since the 1950s. They are recognized as effective and cost-effective additives. They are also controversial additives that the industry and researchers pay more attention to. So that in our feed additive management, there is a special catalogue of medicinal feed additives and usage specifications, but no other special catalogs. A clear understanding of the mechanism of action and effect of antibiotics, as well as related influencing factors, is helpful for us to better replace the antibiotics.
Regarding the mechanism of antibiotics, many researchers and colleagues have conducted experiments, analyses and summaries, and analyzed them from various aspects. However, although there are conclusions in the general direction, some specific mechanisms are still not very clear. Yes, antibiotics that have been used for 60 years are still unclear on the mechanism of ensuring health and promoting growth. But this does not prevent us from analyzing the overall framework and looking for alternatives. Next, I will discuss the mechanism of antibiotics from several aspects
NO.1 A supporting point of the mechanism of action of antibiotics, and two aspects of action
I will use the mechanism diagram published by Kirsty Brown in 2016 to illustrate.
First, the first is the stress, nutrition and environment faced by animals. The basis of the action of antibiotics is the complex microflora and flora in the animal intestines. Coates discovered in 1963 that antibiotics have no effect on sterile animals, which fully shows that the prerequisite for antibiotics to to play a role is that there are various microorganisms in the intestinal tract. This conclusion that everyone can feel with their eyes closed is of practical significance: the condition of intestinal microbes affects the effect of antibiotics. In the previous article (Antibiotic-free series 1), with the changes in modern breeding management, breeds, environment, nutrition, and antibiotic tolerance, the effect of antibiotics on the daily weight gain of growing and finishing pigs from 2000 to 2010 is probably below 2%, the effect of feed conversion efficiency is below 1%, much lower than before 1990. This data is basically consistent with the changes in production performance in Denmark since 2000. Therefore, the first question we need to think about when constructing a replacement program is: what kind of management and nutritional level does my customer or pig farm have, what kind of microbial pressure is facing, what are the expected effects of antibiotics and how big they will be.
Two aspects of the role of antibiotics: 1. Intestinal microflora. 2. The animal itself. Antibiotics in feed can significantly improve the microbial flora in the animal’s intestinal tract. Generally speaking, it can reduce the total microbial species and quantity in the intestinal tract. The abundance of lactic acid bacteria in the distal intestine may be reduced, Ileum lactic acid bacteria and enterobacteria (including Escherichia coli, Salmonella, etc.) will be significantly reduced, the abundance of Clostridium will increase substantially. This also reduces the toxic substances produced by harmful bacteria, such as LPS phosphonate polysaccharides that are decomposed after the death of E. coli. Although most growth-promoting antibiotics target Gram-positive bacteria, they also affect Gram-negative bacteria in the intestinal tract. Limited by previous research methods, many intestinal microorganisms cannot be identified and detected through traditional culture methods. Current DNA high-throughput analysis techniques can identify more microbial flora, such as strict anaerobic rumen cocci and other cellulolytic bacteria. These techniques provide us with an effective means to better understand the intestinal microflora.
For the animal itself, antibiotics can reduce the thickness of the intestinal wall, improve the intestinal morphology, such as the height of villi and the depth of crypts, and increase the utilization of nutrients. In recent years, scholars have begun to pay attention to the effect of antibiotics on the immune response, especially the inflammatory response. Inflammatory response is the normal response of the animal body to microorganisms, especially harmful microorganisms. However, an excessively strong inflammatory response can cause inflammation, aggravate the subclinical ratio and clinical symptoms, mobilize more nutrients for immunity, and reduce feed intake and growth rate. It has been found that AGP can inhibit one or more different links of the inflammatory response, such as the production of chemokines, a variety of reactive oxygen species, and the production of pro-inflammatory cytokines. AGP inhibits inflammation and regulates intestinal immunity, thereby locally improving the morphology of the intestinal epithelium, promoting the absorption and utilization of nutrients, reducing the acute phase reaction at the metabolic level, and reducing catabolism. However, the animal growth is essentially at the expense of the development of the body's immune system, weakening the body's immune function, and preventing the immune system from being activated.
In summary, antibiotics have the following aspects:
A. Impact on the intestinal microflora
1. Reduce the total number of microorganisms in the intestinal tract and change the abundance of different microorganisms.
2. Reduce the degree of subclinical infection.
3. Reduce toxic metabolites produced by harmful bacteria.
B. Effects on the animal body
4. The intestinal wall is thinner and nutrients are absorbed better.
5. Regulate the body's immunity, and control the body's inflammatory response, reduce the immune's consumption of nutrients and the growth of harmful microorganisms.
These two aspects are not completely independent, but interact. The change of microorganisms will affect the immunity of the animal body and the morphology of the intestine, and the change of the animal body will affect the microflora. We can also consider these two aspects when we are working on an alternatives to antibiotics. In the reality I am facing, what work needs to be done to improve the microbial flora, what work to do on the animal body itself, what is the approximate effect, how the combination is more suitable for the breeding situation, and the cost is more acceptable.
NO.2 Postantibiotic effect (PAE)
Two indicators are often used to measure the effect of antibiotics, MIC (Minimum Inhibitory Concentration) and MBC (Minimum Bactericidal Concentration). Many of the actual levels of antibiotics we add to feed exceed the MIC concentration. Another indicator that has attracted a lot of attention in medicine, but the indicator that the animal husbandry industry has begun to pay attention to is the post-antibiotic effect (PAE). The postantibiotic effect means that when antibiotics are in contact with bacteria for a short time, even if the concentration of the drug gradually decreases, below the MIC or after the drug is completely removed, it still has a continuous inhibitory effect on the growth of surviving bacteria. PAE is measured by the time between the control group and the experimental group CFU increase by 1 logarithm (10 times). When permitted by previous regulations, the PAE of the colistin sulfate we often used was 0.5-2.5 hours (Jiang Shanxian, 2003), depending on the amount of addition.
The feeding of animals is not continuous, but has the frequency and times of feeding. The time that chyme passes through the intestinal tract is affected by the type of diet, raw materials and fiber level, and varies from animal to animal. The residence time of chyme in the stomach and intestines of pigs is relatively long, while that of poultry is much shorter. Most of the chyme passes through the small intestine in about 4 hours. In the complex intestinal tract, antibiotics and feed chyme interact with the intestine itself and intestinal microbes, and these effects on antibiotics will be reflected. Although the contribution of PAE to the specific effects of feed drug additives is still unclear, many researchers have also done relevant experiments to confirm the effects of antibiotics at concentrations below MIC for growth promotion and health maintenance.
The postantibiotic effect allows antibiotics to have a more sustained and stable effect in the intestinal tract. When we are making an alternatives to antibiotics, in addition to feeding management, such as the adjustment of feeding frequency, we can also pay certain attention to this, such as the retention and continuous impact of various additives in the intestinal tract.
CONCLUSION
To sum up, we can review and analyze the mechanism of antibiotics when making an alternatives to antibiotics, although some mechanisms are still not very thorough. We should base ourselves on the current situation faced by our customers and pig farms, and start with how to adjust the nutrition plan, regulate the microbial flora, and improve the body's immunity, inflammation and intestinal morphology. In this way, there will be more efficient alternatives. There is no alternative plan that can beat the invincible all over the world, and it needs specific analysis of specific circumstances.
Later, we will discuss the alternative of antibiotics in several aspects, communicate with everyone, and improve together. It is important to note that the above aspects are all interrelated and each has its own independence, and they are not absolutely separate. We discussed separately in order to have a clearer understanding of how to think about alternatives, so please pay more attention to it.
There are so many content, it is inevitable that there will be mistakes, and we will learn and make progress together with everyone!