Host-LBP Interactions: Physiological Challenges

There are intricate and dynamic interactions between live biotherapeutic products (LBPs) and the host microenvironment. These interactions are crucial, as they shape the fate and functions of LBPs. Once administered orally, LBPs encounter numerous physiological challenges. These challenges often hinder their survival, diminish their chances of successful colonization, and impact their therapeutic function.

Physiological Challenges on the Gastrointestinal Tract

Upon entering the stomach, LBPs face an environment replete with acids that can lead to protein denaturation, and enzymes that result in LBP proteolysis. The small intestine continues this chain of adversity with persistence of enzymes and secretion of bile salts. These bile salts perform the function of solubilizing cell wall lipids and proteins. As LBPs arrive in the large intestine or colon area, clearance of LBPs takes place facilitated by defensive immune cells like macrophages. The colon, being the site with the highest number of microbes in the body, offers a highly competitive environment for LBPs. The competition is for both space and nutrients.

Physiological challenges that LBPs will encounter upon oral administration.Fig.1 Physiological challenges that LBPs will encounter upon oral administration. (Heavey, 2021)

In Vitro Conditions and their Challenges

A number of LBPs are fermented under optimal in vitro conditions before administration. They are processed during formulation, stored at diverse temperatures, and expected to quickly adapt to new nutritional sources and chemical environments. The chemical environments could be different depending on varying levels of oxygen or acidity. Here, they compete with resident microbiota that are already evolutionarily equipped to survive and thrive in such conditions.

Dynamic Challenges and Persistent Factors

Several other challenges persist that continually affect LBPs. Peristalsis, the physical contractions that break down and transport food through the gut, results in rapid transit times, thus limiting LBP interactions with target tissues. Mucus and epithelium turnover are dynamic processes affecting the LBP's residence time in the gut. Oxygen gradients and pH in the gut are the other critical influencers. Oxygen levels ranging from 21% in the stomach to nearly 0% in the colon can massively impact LBP metabolism. Similarly, gut pH, which ranges from 1.0-2.5 in the stomach to 6-6.7 in the colon, also significantly influences LBP growth and metabolism. Stomach acids, enzymes, bile salts pose chemical challenges leading to a rapid decrease in viable LBPs.

The challenges posed profoundly affecting the LBPs discovery and delivery. On one hand are chemical challenges like stomach acids, enzymes, and bile salts which reduce the viability of LBPs. Physical challenges like peristalsis and mucus turnover limit LBP colonization or persistence in specific parts of the gut. Competitive challenges like nutrient competition, and space competition affect LBP metabolism and their therapeutic functions. These cumulative challenges make the physiological aspect of LBP discovery arduous, thereby a multitude of avenues for research and development to support advancement in this field.

Creative Biolabs has extensive knowledge and experience in the LBP discovery. If you are interested in our products and services, please do not hesitate to contact us.


  1. Heavey, M. K., et al. Discovery and delivery strategies for engineered live biotherapeutic products. Trends in Biotechnology. 2021, 40(3), 354-369.

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