A new perspective in gut–brain axis: Pay more attention to postbiotic

The gut–brain axis (GBA) refers to the bidirectional communication system between the gastrointestinal tract and the central nervous system. There are two ways for the improvement of the GBA function, either adding probiotics in the diet, which could produce the right metabolites in the gut, or directly adding right metabolites in the diet to facilitate the GBA, the second approach is also called ‘Postbiotic’.

Natthanan Nukitrangsan, PhD
Technical Support Consultant
CP-BIO

The gut–brain axis (GBA) refers to the bidirectional communication system between the gastrointestinal tract and the central nervous system (CNS); it plays a responsible role in mediating neural, immunological, and hormonal signaling. This complex system allows the gut to influence the brain through visceral or animal instincts messages. These visceral messages carried out by the metabolites from cells of the animal itself or gut microbes interact with the enteric nervous system to transduce signals into the brain. In response, signals from the brain influence the gut functions (motor, sensory, and secretory modalities) and immune function (Graph 1). This dual interaction between the gut and the brain not only influences gut physiology but can also provide various health benefits for both human as well as the animals that are raised as food or pets.

Graph 1. Gut–Brain Axis (GBA) modulated by microbe (probiotic) and its metabolites (postbiotic) – Martin et al., 2018

Based on the above understanding, there are two ways for the improvement of the GBA function, either adding probiotics in the diet, which could produce the right metabolites in the gut, or directly adding right metabolites in the diet to facilitate the GBA, the second approach is also called “Postbiotic”. Many research articles and commercial products are available, and Table 1 lists few examples. I used the term “microbiota” for probiotic, meaning the product is a live cell or the spore of the cell, which could survive and produce the correct metabolites in the gut. Metabolites, or postbiotic is the feed additive which is produced by a probiotic by using fermentation technology.

Although both microbiota and the metabolites used for GBA modulation are effective and encouraging, there are differences in terms of active ingredients, quality control by end-users and safety issues between these two kinds of products. Microbiota are live cells or the spores of probiotic bacteria, they are supposed to produce the right metabolites in gastrointestinal track of animal but the disadvantages would be the followings: (1) active ingredient produced inside the gut may not be appropriate in quantity, (2) difficult to do quality control by end-users, (3) may have safety issues if the critical mutation happens if any. On the contrary, the metabolites do not have these concerns (Table 2). Because the production of metabolites by a GMP factory has a strict compliance with GMP production management, while the microbiota product is almost impossible to do that due to all kinds of uncertainty inside gastrointestinal track of animal.

In this paper, I would like to introduce two neuroactive molecules, GABA (ƴ-aminobutyric acid) and IAB (sodium butyrate) as feed additive for performance improvement of poultry broiler. Graph 2 describe a proposed metabolites modulator for GBA, using GABA and IAB as example in broiler chickens. GABA is a neurotransmitter, which can go to the brain through central nervous system (CNS), while IAB is an energy source for gut epithelium cells so it can produce more endogenous neurotransmitters as well immune cells. When gut epithelium cells produce more endogenous neurotransmitters as well as immune factors (such as cytokins), the later is part of the immune power of the bird. Both endogenous and exogenous neurotransmitters send vagal and spinal signals to CNS. This helps the brain to react for handling stress of the adverse conditions of undesirable environment or rough and strict management (e.g. beak trimming). On the other hand, brain also can use autonomic nervous system (ANS) to modulate gut function and enterochromaffin cell (ECC), so more luminal hippocampal serotonin (5-HT) can be released. This results in more probiotic bacteria in gastrointestinal track. The combination of GABA and IAB makes the process more efficient.

Graph 2. A proposed postbiotic modulator for GBA, using GABA and IAB as example in broiler chickens

There are many separate research by using GABA or IAB (sodium butyrate) for improvement of poultry production, but what I did recently is probably the first effort by using GABA and IAB together in poultry broiler. Table 3 is the summary of two preliminary poultry trials by using GABA and IAB in closed poultry farm in Thailand. The results show that GABA and IAB working together can give a significant improvement in feed conversion ratio (FCR) for broiler chicken, although the body weights between the control and treatment group did not show difference. In my study, I found out that GABA and IAB along did not give FCR reduction in trial II. But this does not trouble me as I am sure if more studies performed and the idea dosage could come out under the particular situation that I am doing the trial, as many other research reported many good results by using either GABA or IAB along in poultry broiler and other food animals. However, considering the improvement of 5.4 – 7.1% in FCR based on my preliminary trail result, and the fact that 2/3 of meat production costs is the feed, the reduction of FCR by using GABA and IAB together is definitely worthy for conducting more investigations.

It is also interesting to know that our results are mostly in line with the trial results with other similar study, such as Chen (2015), Chand (2016), El-Naggar (2019), Zhong (2020), who reported an 8 – 9% FCR reduction by using GABA in poultry feeds when the birds were raised at warm or high temperature environment.

CONCLUSION AND OUTLOOK
We believe that using postbiotic approach, metabolites such as GABA and IAB produced in GMP factory for the purpose of GBA modulation is a better choice, than probiotic approach, as microbiota is unlikely to be easily controlled inside the GI track. Therefore, I think the postbiotic approach has better future in poultry production. CP-Bio has the world class fermentation capacity which ensures the quality and the quantity needed for healthier animals and the safer food production for mankind.

References are available on request.