Sampling the Intestinal Microbiome Through an Ingestible Pill: A Recent Breakthrough

The gut microbiome has been a hot topic in recent medical research. Its impact on overall health and associations with diseases have brought it to the forefront of focus. However, there is still a large knowledge gap to fill regarding the trillions of gut microorganisms and their functions. Recent development of a 3D-printed pill has the potential to help scientists improve understanding of which bacterial species truly reside in our gut through more accurate sampling. If successful, this could lead to an evolution of preventive medicine and disease treatment. 

Development and Roles of the Intestinal Microbiome

To realize the importance of sampling gut microbiota, it is necessary to first understand the roles of these organisms in health and disease. An immense number of microorganisms reside in our GI tract, spanning from the mouth to the colon. In fact, the amount of commensal GI microbiota is 10 times greater than the total number of cells in the human body. Over 1000 individual species have been discovered so far, but there are 2 overwhelmingly dominant families of bacteria, the Bacteroidetes and the Firmicutes, that greatly outnumber the others.

The development of the gut microenvironment begins at birth, when an infant is exposed to a mother’s flora. From that point forward, a wide variety of factors, including diet, aging, lifestyle choices such as physical activity frequency, medication use (especially of antibiotics), stress levels, and environmental exposures are thought to influence the composition of the microbiome. The relative abundances of different microbial species have been found to immensely impact human health. 

Some of the key functions gut bacteria take on in the human body include:

• Digestion: So-called “good” bacteria in the gut play a role in breaking down otherwise indigestible compounds, such as fiber. 
• Synthetic function: Some species of gut microorganisms can synthesize vitamin and amino acids and carry out important chemical reactions involving bile.
• Host immune system maturation: Gut bacteria and the metabolites they produce can help the host immune system within the GI tract mature and develop.
• Protection from pathogens: Beneficial gut bacteria can outcompete pathogens for nutrition or binding sites on the intestinal wall, providing a first line of defense against infection. 
• Interaction with the brain via the gut-brain axis: Commensals in the gut can interact with the central nervous system, the endocrine system, and the immune system through complex, bidirectional signaling pathways. There is a great deal left to learn about this intriguing interaction and its higher purposes. 

Disease Associations of Dysbiosis

Evidently, a healthy gut microbiome carries out a host of vital functions that we ourselves could not otherwise execute.  On the other hand, when there is an imbalance in the microorganisms that make up our GI flora, termed dysbiosis, serious health consequences can result. The gut microbiome has recently been found to be implicated in a plethora of diseases. Some examples of pathologies most strongly associated with gut microbiome dysfunction include:

• Irritable bowel syndrome: The etiology of this disorder was unclear since its discovery, but gut-brain axis interactions have now been shown to have a major role in its pathogenesis.
• Irritable bowel disease: IBD, including Crohn’s disease and ulcerative colitis, have also been associated with dysbiosis. Interestingly, fecal transfers of healthy gut flora from donors to IBD patients have resulted in complete recovery, suggesting that gut microbiome is a significant factor in IBD pathophysiology. 
• Obesity, diabetes, and metabolic syndrome: Recent research has revealed notable differences in the gut flora of mice with an induced metabolic syndrome and healthy mice. This indicates that dysbiosis is also involved in metabolic diseases, potentially due to loss of the commensal organisms’ beneficial metabolic functions.
• Allergic diseases: Food allergies, asthma, and allergic diseases such as eczema and psoriasis have also been associated with poor gut microbiome function. The prevalence of such allergic diseases has increased over the past 50 years, raising questions of whether lifestyle-associated gut microbiome changes may be to blame.

Research Limitations

The explosion of recent research regarding the gut microbiome has led to discoveries of interesting disease associations and complex interactions between the immune system, nervous system, endocrine system, and gut microorganisms. However, knowledge of which organisms are present in the gut and their functions in health and disease is far from complete. This is a consequence of two main limitations: first, cost, and second, lack of an efficient, noninvasive method for sampling the gut microbiome. Invasive methods lack a risk-benefit justification, and ingestible devices that have been developed thus far are complex and often fail due to sample contamination. Thus current methods of assessing gut microbiome composition rely mainly on inference based on stool samples, which favors the colon flora. Although the insight gained from this method has been valuable, other, more accurate sampling strategies are necessary to further our understanding from this point.

A New Way to Sample the Gut Microbiome

In hopes of accomplishing this much-needed goal, Del-Rio-Ruiz et al. have devised a 3D printed, ingestible pill that is intelligently designed to obtain microbial samples from the small intestine. The device, shaped like a pill capsule, is lightweight, flexible, and resistant to destruction by the highly acidic environment of the GI tract. 

It operates by pH-triggered sidewalls that open when they reach the small intestine specifically. Beads from the sides of the device expand and dissolve a small area of the intestinal coating in order to obtain the sample. The beads automatically close when collection has concluded in order to avoid contamination by colonic flora as the pill is excreted. 

A series of experiments conducted on mice, pigs, and hounds determined that the locking mechanism is effective, the device does not show any measurable contamination, and, most importantly, that the samples it collects do not differ significantly from invasive samples of animal GI tracts. This is the first non-invasive, effective device that has successfully collected a small intestinal sample. However, its efficacy in humans is yet to be determined. 

Conclusions

The gut microbiome, consisting of trillions of microorganisms throughout the GI system, plays significant roles in maintaining human health. The gut flora interacts with various other organ systems, and when dysregulated, it can contribute to numerous gastrointestinal and systemic diseases. However, our current knowledge of which bacteria inhabit different parts of the GI tract has thus far been limited by lack of an effective, inexpensive, and non-invasive sampling modality. The new 3D-printed, ingestible pill recently developed by Del-Rio-Ruiz and colleagues shows significant promise for obtaining microbial samples from the small intestine, a previously unexplored area. This has the potential to change our understanding of physiology and pathophysiology of the gut microenvironment and influence future disease management.

Summary

A novel 3D-printed, ingestible pill has recently been developed to enhance our understanding of the gut microbiome. Current knowledge about the gut flora, which plays a crucial role in digestion, immunity, and interaction with other organ systems, is limited by the difficulty of accessing microbial samples from specific GI tract regions. Most sampling methods rely on stool samples, which are biased towards colon bacteria. The new pill is designed to release sampling beads in the small intestine. These beads collect bacteria samples without downstream contamination, making the device more reliable than stool samples or previous attempts at non-invasive sampling. Early animal tests suggest it successfully captures microbial profiles similar to those obtained via invasive methods, though human testing is still needed. This breakthrough could advance our understanding of the gut microbiome’s role in health and disease, potentially leading to improved disease prevention and treatments.