Microbiota-host interactions. How can dietary strategies help?

Introduction

Food production animals, have been genetically selected towards improved parameters like: feed intake, muscle development, and  milk or egg production. In addition, these animals are reared in conditions that tend to favor pathogen dissemination. High feed uptake rates and quick growth make these animals prone to intestinal disorders, which in the past was disguised up to a certain extent with the use of antimicrobial growth promoters (AGPs).

These compounds were widely used around the globe to maintain profitability in the broiler and pig industries.The inclusion of antimicrobials at sub-therapeutic levels as feed additives, led to increased animal performance. However, such practices also contributed to an increased onset of antimicrobial resistance (AMR), posing very serious health risks for people and animals.

AGP bans: Discoveries behind a very important measure

A ban on the use of AGPs, mainly driven by consumer concerns regarding increases in antimicrobial resistance, was installed in the EU in 2006. This became a global trend and concerns led to use reductions or bans depending on the region. In 2012 the Center for Veterinary Medicine of the US Food and Drug Administration published a ‘Guide for the Industry’ where they stated that antibiotic use must be reserved for disease treatment in specific situations, and not for growth promoting purposes.

The mode of action of AGPs is still a matter of discussion, but a variety of mechanisms have been suggested, including: total bacterial count reduction in the gut (and consequently less competition for nutrients), a reduction of specific pathogens (e.g. Clostridium perfringens), a decreased abundance of specific harmful bacterial properties (e.g. bile salt hydrolase activity and thus poor fat digestion), a reduction of inflammatory reactions associated with a decreased pathogen load, amongst others (Butaye et al., 2003; Knarreborg et al., 2004). Direct immune-modulatory effects associated to AGPs have also been suggested.

Regardless of what the action mechanism of AGPS is, it is evident that host-microbiota interactions are involved. Gut-microbiota interactions are very complex since the gut is an organ that contains multiple cell types that carry out multiple functions. While also serving as a host to a diverse microbiota which also carry out many functions, including the breakdown of dietary molecules and the subsequent production of absorbable products. As well influencing and modifying the maturation and development of the (mucosal) immune system.

 

Unlocking the potential of the gut microbiome

The term ‘gut ecosystem’ describes the fact that microbiota is part of a single organ, with specific functions. Such functions derive from both the genetic potential of gut microbiota (microbiome), and the functions of the host gut wall. The recent application of novel technologies (-omics technologies) has allowed to obtain a better understanding of host-microbiota interactions. Various studies using 16S rDNA sequencing, specifically led to the identification of microbial taxa associated with beneficial or harmful host responses. Meanwhile the use of metabolomics has allowed the identification of the microbial metabolites that trigger such effects. The production of microbial metabolites can be influenced through the use of nutritional factors. This presents an unprecedented opportunity to make animals more robust and resilient against non-infectious and infectious challenges. Which can potentially result in significant health and productive benefits.

 

 

Importance of the host: Major signal sensors in epithelial cells

When comparing the gasotintesninal tracts of poultry, pigs and cattle, there are obvious anatomical and morphological differences between these species. Cattle possess a significant difference considering the fact that they present forestomachs. However, although the rumen is a key fermentation chamber in adult cattle, calves fed on liquid diets (veal calves) do not develop forestomaches and can be considered as monogastrics, similar to chickens and pigs.

Despite anatomical and morphological differences, the cell types present in the gut wall of these animal species are very similar. The luminal side of the intestinal wall is lined with absorptive epithelial cells, whose major role is water and nutrient absorption, and enzyme secretion. These cells form a semi-permeable barrier between the external environment (the gut lumen) and the internal host tissues. This semi-permeable barrier is not only formed by the cell membranes of epithelial cells, but also by the tight junctions connecting neighboring epithelial cells (Piche, 2014). These connections are in turn regulated at different levels by cytokines and other factors.

The permeability of the intestinal epithelial cell layer can be affected by epithelial cell death but also by luminal signals that increase permeability by affecting tight junctions or inducing cell death. Resulting in the loss of integrity of this key barrier between the ‘inside’ and the ‘outside’ of the gut (Hooper, 2015). Loss of intestinal integrity can cause host protein losses (‘leaky gut’) into the lumen and can allow luminal molecules (including toxins) and microorganisms to reach the gut submucosa. Some of these components possess pro-inflammatory properties, which can lead to massive immune cell infiltration which implies high energy demands for the host.

Inflammation

Inflammation is mediated by binding of pathogen associated molecular patterns (e.g. LPS, peptidoglycan lipoproteins, flagellin) to receptors (e.g. Toll like receptors (TLRs)) that transmit signals in a cascade ultimately leading to inflammatory cell infiltration in the mucosa (Brown et al., 2011). Although this is a protective response, this inflammatory cascade should be brought back to normal conditions when the trigger is eliminated. Also intracellular receptors (NOD-like receptors) can sense bacterial compounds and can even induce tolerance (eg. peptidoglycan-derived muramyldipeptides (MDPs)). Apart from absorptive epithelial cells, also other epithelial cell types are present in the lining of the gut wall. These include mucin-producing goblet cells and antimicrobial peptide producing Paneth cells (in the crypts, not present in all animal species), important in innate defenses (Muniz et al., 2012). Below the epithelial lining, many other cell types are present that form the lamina propria of the intestinal mucosa. These are immune cells, fibroblasts, nerve cells and muscle cells, amongst others.

Importance of intestinal integrity and gut function equilibrium

Intestinal integrity, inflammation and gut function are all influenced by luminal signals. Many of these signals are produced by the microbiota (Havenaar, 2011). The aforementioned cells, sense microbial signals and transmit these signals to other cell types and to other areas within the animal’s body. Therefore, microbiota composition and bacterial metabolites are crucial in maintaining animal health and productivity.

This entry will be continued in a subsequent publication…

Abstract modified from:  Proceedings of the Animal Nutrition Conference of Canada 2020. Author/s: Filip Van Immerseel / Department of Pathology, Bacteriology and Avian Diseases Faculty of Veterinary Medicine, Ghent University, Belgium.