The gut plays a critical role in animal health and well-being, housing a vastly complex community of microorganisms. Inoculation occurs immediately after birth, with diversity and complexity increasing until the microbial ecosystem has reached a relatively steady state. This diversity is crucial to the gut’s function as a protective barrier and provides resistance to colonization of pathogenic organisms, such as Salmonella, Escherichia and Campylobacter, as well as exerting beneficial effects on immune function.
The role of the gut microbiota
The gut microbiota can vary greatly between individuals, depending on genotype, age, environmental factors, diet and use of antimicrobials. However, despite this variation, approximately 90 percent of the contributing organisms are of the phyla Bacteriodetes and Firmicutes.
The microbial community within the gut is involved in pathogen control, immune function, nutrient provision and intestinal morphology. It can also profoundly influence the health of the host and has been implicated in many disease states.
Animals are born with no effective gut microbiota. Inoculation and colonization begin to occur immediately after birth. Colonization educates the immune system and moderates its reaction to antigens, while providing nutrients, such as some vitamins and amino acids, as well as short-chain fatty acids. Butyrate, for example, is known to have a beneficial effect on enterocyte structure and function. It is well established that the gut microbiota can have a significant role in food component digestion and absorption and can have a positive effect on energy release from the diet.
A diverse population of commensal bacteria can inhibit enteropathogens colonizing and infecting the gut, a function termed “colonization resistance.” Effective colonization resistance requires a highly diverse and complex microbiota. Animals with low diversity are likely more susceptible to enteric pathologies. Reduced gut microbial diversity increases the risk of colonization of pathogenic bacteria, resulting in gut inflammation and a potentially systemic response.
For example, one study used a mouse infection model to demonstrate that mice with a low complexity gut microbiota were more susceptible to Salmonella enterica-induced enterocolitis compared with conventional mice. Furthermore, they showed that, after these mice had been housed with conventional mice for 21 days, their gut microbiota complexity was increased and resistance to S. enterica partially restored. The authors also found that closely related phylotypes generally display correlated abundances and can be used as a predictor of susceptibility to intestinal colonization of pathogenic and commensal bacteria.
There is evidence to suggest modulation of immune function by the gut microbiota. Gut microbes modulate expression of certain receptors in the gut that affect gut permeability. Imbalances in gut microbiota can lead to increased gut permeability and unregulated proinflammatory cytokines, as well as metabolic endotoxemia and insulin resistance. The Actinobacteria, Bifidobacterium spp. have been reported to protect gut barrier functions, and supplementation of these species has resulted in reduced gut permeability and reduced endotoxin-producing bacteria.
In recent years, a plethora of technologies have been developed that have allowed us to further the understanding of the inhabitants of the gut. They have given us the ability to look beyond simple culturing and begin to investigate not only phyla and species present but also their potential contribution in terms of function. The majority of these have been termed the ‘omics’ technologies and include genomics, metagenomics, metatranscriptomics, metaproteomics and metabolomics.
- Genomics, the study of genomes, includes the sequencing, mapping and analysis of individual genomes.
- Metagenomics refers to sequencing and analyzing a collection of genes from the environment in the same way single genomes are analyzed. Such a technique allows us to capture the complexity of microbial diversity that we would have otherwise failed to spot and is a powerful analytical technique.
- Metatranscriptomics allows us to evaluate diversity and potential functional capacity of microbiomes and profiles those genes that are expressed via messenger RNA (mRNA).
- Metaproteomics and metabolomics are the study of proteins and metabolism in the form of metabolites, respectively. Both are relatively new techniques but are capable of expanding our knowledge of the functional capacity of the microbial community in the gut. Also important is how the data generated from these techniques are analyzed and interpreted.
- Bioinformatics is a rapidly growing field of study and aims to understand and interpret the results from above techniques using modeling and software.
Numerous factors affect the gut microbiota. They can be broadly categorized into three classes: host-associated, biotic and abiotic.
Host-associated factors include the host's own genetic makeup, and heritable taxa have been identified. The host’s immune system also plays a role. By far the most influential factors are environmental and food source. Host lifestyle and diet play a key role in development and maintenance of the gut microbiota with environmental sources of microbes contributing to colonization immediately after birth.
Diet and medication have a significant impact on the microbial community within the gut, with medications accounting for the greatest variation between individuals. For example, diet is the major determinant of rumen bacterial community structure. Medication including, but not limited to, antibiotics has a significant impact on gut microbiota and, subsequently, host health. Antibiotic use results in changes in the intestinal microbiota and a reduction in diversity and complexity due to their non-specific action.
Subsequently, colonization resistance decreases, and animals are rendered more susceptible to enteric pathogens. This reduction in colonization resistance has been implicated in one of the greatest threats of this and subsequent generations — antimicrobial resistance.
Antimicrobial resistance (AMR) is not a new phenomenon. It has always been present, however, the current, and potentially increasing, level of resistance is alarming, and reports exist to highlight the severity of the issue.
Consequently, there is global pressure to reduce the level of antimicrobials used in human and animal medicine and to restrict the use of antibiotics in animals to therapeutic use only. Livestock production is often cited as the largest user of antimicrobials and, in 2006, the use of antibiotics as growth promoters was banned in Europe.
To compound the issue, few pharmaceutical companies are actively involved in antibiotic research and there is a lack of new and emerging antibiotics. Worryingly, even with a decline in the use of antimicrobials, there is still antibiotic resistance in animals that have not had antibiotic growth promoters (AGP) and thus simple restrictions are not enough to combat resistance.
Feed additives solutions
Restoring and enhancing diversity of the microbiota can be used in the arsenal against AMR. There are numerous nutritional supplements that target intestinal health with the aim of stabilizing the gut flora and reducing the susceptibility of the host to disease, including prebiotics, probiotics, enzymes and plant extracts.
There is an extensive body of work in animals, such as poultry, looking at the effect of various prebiotics, such as inulin, fructo-oligosaccharides (FOS) and mannan-oligosaccharides (MOS) on gut microbiota. MOS, in particular, have demonstrated consistent and reproducible benefits to the gut microbiota of chickens.
The gut microbiota has significant influence on host health, immunity and physiology and can play a role in reducing reliance on antimicrobials. However, a diverse and complex microbiota is required in order to maximize resistance against colonization of pathogenic species and the reduction in susceptibility to disease. Many dietary interventions exist that could improve diversity in the intestinal microbiota.
References available upon request.