Indole is an aromatic, heterocyclic organic compound with a dual nature regarding its scent. In high concentrations, it has an intense fecal odor, yet in very dilute solutions, it contributes to the fragrance of flowers like jasmine. First isolated in 1866, its name combines “indigo” and “oleum,” referencing its origin from indigo dye. Beyond its varied smells, indole is a signaling molecule produced by life forms from bacteria to plants and plays a part in animal physiology through the gut microbiome.
The Biochemical Route to Indole
The primary production pathway for indole begins with the essential amino acid tryptophan, which animals must obtain from their diet. The conversion is carried out by the enzyme tryptophanase in a reaction that breaks down tryptophan into indole, pyruvate, and ammonia.
In the world of bacteria, the gene responsible for producing the tryptophanase enzyme is identified as tnaA. The presence of this gene is a strong indicator that a bacterial species can generate indole.
While the tryptophanase pathway is the most recognized route, indole can also be part of more complex molecules. For instance, plants synthesize the growth hormone indole-3-acetic acid (IAA) from tryptophan, a process where indole serves as a core structural component. However, the direct cleavage of tryptophan to free indole by tryptophanase remains the most direct biochemical route for its production, especially within microbial communities.
Indole Production Across Life Forms
The capacity to produce indole is not confined to a single domain of life; it is a trait observed in organisms from bacteria to plants. A substantial portion of biologically active indole originates from bacteria. Species such as Escherichia coli, along with members of the Clostridium, Proteus, and Bacillus genera, are well-known indole producers. These bacteria are abundant in the gastrointestinal tracts of animals, making the gut a major site of indole synthesis, though they are also found in soil and aquatic systems.
In the plant kingdom, indole is foundational to the synthesis of auxins, a class of growth hormones. The most studied auxin, indole-3-acetic acid (IAA), is involved in processes like root development and fruit growth. Plants use tryptophan to create IAA, meaning that while the indole structure is central to these hormones, plants do not release large amounts of free indole in the same way bacteria do.
Certain fungi are also capable of synthesizing indole or indole-containing compounds. These molecules often function as secondary metabolites that may offer an environmental advantage.
Indole’s Diverse Biological Roles
Indole acts as a signaling molecule that influences the behavior of its producers and their neighbors. Within bacterial communities, indole regulates a variety of physiological processes. It can impact biofilm formation—the process of bacteria adhering to surfaces—and also plays a part in modulating virulence, antibiotic resistance, and the formation of spores.
The influence of indole extends beyond bacterial interactions to communication between gut microbes and their hosts. Indole produced by gut bacteria can be absorbed by the host and has been shown to strengthen the intestinal epithelial barrier. It achieves this by affecting the proteins that form tight junctions, which are structures that seal the space between cells lining the gut and help prevent unwanted substances from leaking into the bloodstream.
Indole can also modulate the host’s immune system, often exerting anti-inflammatory effects and influencing the activity of various immune cells. This communication between gut bacteria and the host immune system is an active area of research, exploring how microbial-derived indole helps maintain a balanced immune state.
Modulating Indole Levels and Their Significance
The concentration of indole within the gut is not static and can be influenced by several factors. Diet plays a direct role, as the availability of tryptophan from protein-rich foods determines the raw material available for gut bacteria to convert into indole. Dietary fiber also has an indirect effect by shaping the composition of the gut microbiota, potentially favoring the growth of indole-producing bacteria.
The specific types and numbers of indole-producing bacteria present in the gut are a primary factor in indole levels. An imbalance in the gut microbiota, or dysbiosis, can result from illness or stress and lead to altered indole production. The use of antibiotics can also impact indole synthesis by reducing the populations of bacteria responsible for its production.
Changes in indole levels can have meaningful consequences for the host. Reduced indole concentrations might compromise the integrity of the gut barrier, making it more permeable. Conversely, shifts in indole levels are being investigated for their association with various health conditions. Understanding how to modulate indole production through diet or other interventions is a growing field of interest for maintaining overall gut health.