The Effect of Antibiotics on the Gut Microbiome

• The spectrum of the antibiotic used. Narrow spectrum antibiotics are expected to have a lesser effect than broad spectrum antibiotics
• The bactericidal effect of antibiotics irreversibly kills bacteria, including intestinal bacteria
• Hind gut activity: some antibiotics do not reach or are inactive in the large intestine where the majority of the flora are located

Based upon these parameters, Pharmasin® / Tylovet®, Vetmulin® / Rodotium® and Tilmovet® will only have a minor effect on the intestinal microbiome.

For products with an expected moderate effect on the gut microbiome, correct use will help to minimize that effect.

Consider probiotics, such as Top Gut® / Miya Gold® and B-Act® that can be beneficial in restoring the gut microbiome after antibiotic treatment.

The development of antibiotics is one of the greatest medical advances of the 20th century, saving millions of lives. Although most antibiotic treatments do not cause any adverse effects, the potential negative side-effects, such as antimicrobial resistance (AMR) and the influence on the microbiome, have only been of interest in the past few decades.

Most of the early research focused on the influence of the antibiotic on the pathogenic bacteria for which they are intended and registered. One of the reasons is that the standard method for bacterial research was in vitro culturing, a method that is not suitable for gut bacteria since 99% of them cannot be cultured in vitro. In addition, the microbiome is a symbiosis of bacteria, yeast, viruses, and protozoa all interacting and having functional and metabolic networks.

Another factor complicating research is that there is variability of the microbiome influenced by a number of factors including age, feed composition, water quality, stress factors, genetics, infections, inflammatory processes and therapeutic interventions such as antibiotic treatment. In this article, the influence of antibiotic treatment on the gut microbiome and how it can be effectively managed will be discussed.

Antibiotic treatment is, and will remain, a requirement for the treatment of bacterial infectious diseases to avoid animal suffering and mortality. The first criteria for selecting an antibiotic for treatment should depend on the expected efficacy, based on a proper diagnosis and, if possible, an antibiogram. It is, however, also useful to have some understanding of the potential influence of the antibiotic on the gut microbiome and how this can be limited as much as possible. Some basic knowledge of the pig microbiome and antibiotics can help here.

The first important point to consider is how broad the antibiotic activity is. This is also called the 'bacterial spectrum'. Little is known of the susceptibility of the normal bacterial community in the gut to antibiotics, so classification should be based upon the spectrum of activity on pathogenic bacteria, where most research has been done. Broad-spectrum antibiotics will potentially pose a bigger risk for the microflora than narrow spectrum antibiotics (Figure 1). 

Figure 1. Classification of commonly used antibiotics in livestock, based on their activity against common pathogenic bacteria (Gram-negative, Gram-positive, aerobic, and anaerobic)

Secondly, it is important to consider that the largest volume of gut microorganisms is located in the hind gut, meaning that any antibiotic that is very active in this part of the intestine will have a bigger impact on the microflora than antibiotics with little activity in the hind gut. Any disturbance of the anaerobic hindgut microflora can lead to a proliferation of pathogens that are resident in the large intestine, which will then move up towards the small intestine, causing disease. A typical example is post-weaning E. coli diarrhoea. Some antibiotics are inactive in an anaerobic environment, meaning that these are not the best choice for infections in the anaerobic large intestine. That said, treatment with these antibiotics will consequently have little effect on the microflora situated here. A typical example is Apravet® (apramycin) which can be used for E. coli infections, typically in the small intestine, without influencing the hind gut microflora.

Thirdly, antibiotics are classified as bactericidal or bacteriostatic. Bactericidal antibiotics kill bacterial irreversibly, whilst bacteriostatic antibiotics have a reversible effect by temporarily inhibiting the growth of a certain bacterial population. Bactericidal antibiotics should, for this reason, be considered more risky towards the gut microbiome.

Bringing together the above risk factors can help to estimate the potential effect of the antibiotic on the bacterial gut microbiome. Narrow spectrum, bacteriostatic antibiotics with no hind gut activity would have the ideal profile with regards to their effect on the microbiome, whilst broad spectrum, bacteriocidal antibiotics with hind gut activity are expected to cause major shifts in the microbiome (Figure 2). 

The correct use of antibiotics is not only important from an efficacy point of view; the choice of antibiotic can also help to minimize the effect on the gut microbiome. The effect further depends on application (dose, duration, application route) and product quality (pharmacokinetic behaviour). The latter should not be underestimated as product formulation has a major impact on the pharmacokinetic behaviour of the antibiotic and consequently, the antibiotic concentrations reached in each part of the body, including the hind gut.

Figure 2. Classification of antibiotics with regards to their potential effect on the microbiome, based on their spectrum, hind gut activity and bactericidal activity

In conclusion, the choice of an antibiotic should depend on the expected efficacy against the targeted pathogen. However, it might also be important to consider the effect on the gut microbiome to avoid the proliferation of harmful bacteria after antibiotic treatment because of gut microbiome disturbance. Also consider probiotics, such as Top Gut® / Miya Gold® and B-Act® that can be beneficial in restoring the gut microbiome after antibiotic treatment.