Figure 1, Key Figure. Physiological Challenges in the Human Gut.

Upon oral administration, LBPs will encounter various physiological challenges during passage from the stomach (blue), through the small intestine (yellow), and to the colon/large intestine (purple). There are a variety of chemical challenges secreted in the gut, such as (a) acid (stomach), (b) digestive enzymes (stomach and small intestine), and (c) bile salts (small intestine) which either disrupt essential LBP components (e.g., cell wall) or cause internal stresses that lead to LBP death. (d) Immune cells in the gut (small intestine and colon) can actively sense, interact with, and clear exogeneous LBPs. Competition, arising from the existing microbiota (large intestine), can limit LBPs ability to access sufficient (e) nutrients, for growth and metabolism, or (f) space, for adherence, growth, and colonization. Physiological challenges can also be ubiquitously encountered through the gut such as chemical gradients (g) (pH and oxygen) or physical phenomena including (h) peristalsis and (i) epithelial/mucosal turnover. These physiological aspects, and how they serve as challenges to LBPs upon oral administration, are discussed in more detail in Box 1.