Unique Bacillus strain: Effective to enhance immuno-responses

Dr. Y G Liu and Dr. Claire Xu, Adisseo Asia Pacific Pte Ltd, Singapore


Summary Bacillus subtilis DSM 29784 (Alterion®) has shown anti-inflammatory property, similar to commonly used antibiotics in feeds. In addition, it is able to maintain the intestinal barrier integrity against intrusion, which is critical to ensure gut health.


The growth promotion effect of antibiotics was largely proven and is commonly used in animal production. In recent years, more and more countries are making efforts to promote responsible usage of antibiotics, by government regulations as well as key stake-holders in the animal industry. Apart from treatment for infectious diseases, there is a strong trend to ban antibiotics as prophylactic use and growth promoters. In Asia, following South Korea, Thailand and Philippines, Vietnam and Indonesia also joined the band since Jan 1, 2018.

For antibiotics, besides their anti-microbial effect, their connection between growth promotion and anti-inflammation effect was discovered by Prof. Theo Niewold (2007), who further demonstrated that all antibiotics used as AGPs also have anti-inflammatory properties (Fig 1).

Figure 1. Table summarizing the relationship between anti-inflammatory effect and growth promotion effect of different types of antibiotics. Adapted from Niewold 2007.

Bacillus Probiotic Enhances Immunity by Anti-inflammatory Effect

Probiotics have been recognized and widely used as one of most effective AGP alternative solutions. In order to check their direct anti-inflammatory properties, an in vitro model is used - a human intestinal epithelial cells (Caco-2) monolayer established in a Transwell system. Bacillus subtilis DSM 29784 (Alterion®) was tested and compared with two other Bacillus subtilis strains found in commercial probiotic products (named Bs A and Bs B), benchmarked by epigallocatechin gallate (EGCG) as strong anti-inflammatory compound.

The Caco-2 cells were then stimulated by exposing to interleukin 1 beta (IL-1 beta), an inducer to mimic inflammatory response. The level of inflammatory response was measured against the production of interleukin 8 (IL-8), a marker of acute inflammation. 

As shown in Fig 2, upon stimulation of the Caco-2 cells with IL-1, a huge increase in IL8 production was observed (negative control - non-stressed cells vs positive control - stressed cells), and EGCG was very effective in preventing the inflammatory response. Even though all Bacillus strains tended to reduce inflammatory response, Bacillus subtilis DSM 29784 was much more effective, decreasing the production of IL-8 to the level obtained with EGCG (Fig 2).

Figure 2. Caco-2 cells IL-8 production under IL-1 stimulation (+ negative and positive controls)


Bacillus Probiotic Enhances Immunity by Better Intestinal Barrier
Intestinal barrier integrity is also critical for the performance and health of the animals, via better nutrient absorption and protecting the animals' immune systems against bacteria and toxins entering the bloodstream.

The same Caco-2 model was used to test the direct effect of Bacillus subtilis DSM 29784 on intestinal barrier function, with stimulation by TNF-α, a pro-inflammatory molecule that can lead to impairment of the intestinal barrier integrity. Transepithelial electrical resistance (TEER, voltage between the apical and basolateral side) was measured, corresponding to the passage of the molecules. The higher the TEER, the better the integrity. In addition, paracellular pathway with D-mannitol was also monitored to further evaluate the integrity of the intestinal barrier. More D-mannitol passing from apical to basolateral means that the integrity of the barrier is damaged.


As expected, the stimulation with TNF-a decreased TEER and increased D-Mannitol flux.  Bacillus subtilis DSM 29784 was able to restore both parameters to levels similar to non-stimulated cells (Fig 3).

Figure 3. TEER and D-mannitol fluxes measurements


In summary, Bacillus subtilis DSM 29784 (Alterion®) has been demonstrated to enhance immunity system via strong anti-inflammatory properties, as observed with most antibiotics used as AGPs, and better gut barrier integrity, to ensure optimal performance as well as good health status in livestock.


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Article made possible through the contribution of Dr. Y G Liu, Dr. Claire Xu and Adisseo Asia Pacific Pte Ltd, Singapore