10¹⁴. It’s a large number – one hundred trillion to be exact. To put that into perspective, one year contains approximately 3.15 × 10⁷ seconds, so to get to 10¹⁴ seconds, that would take about three million years.

But, 10¹⁴ is also the number of bacteria living in the gut microbiome (Zhang et al., 2025). It is estimated that more than 3,000 species inhabit the space (Zhou et al., 2024). Because the gut microbiome varies, it is difficult to know what a “normal” gut looks like. However, changes in the gut microbiome seem to affect mood and health. In fact, growing research has demonstrated that the brain and the gut are in constant communication (a phenomenon known as the gut-brain axis), with a study from Nature Mental Health finding biological patterns in the microbiomes of people who are highly resilient in the face of stressful events (Chen et al., 2024). In those who were more resilient to stress (as determined by a psychological assessment), the activity in their gut microbiome—encompassing the secretion of short chain fatty acids—was linked to reduced inflammation and improved gut barrier integrity.

In addition, gut microbiota secrete neurotransmitters, with 90% of serotonin (which is heavily involved in regulating mood) being produced in the gut (Godoy, 2024). Given that a lot of this research is new, more work will need to be done to determine whether changes in the gut microbiome cause disease. We’re definitely far away from “probiotic treatments” for stress, but being a biomedical engineering student, I wonder if we could use the gut microbiome’s other properties—such as their ability to secrete short chain fatty acids, among other molecules—to engineer treatments, especially in the digestive health space?

Research Into Gut Therapeutics

Inflammatory bowel disease (IBD) is a chronic condition characterized by inflammation of the digestive tract, with the two main subtypes being Crohn’s Disease (affecting any part of the digestive tract) and Ulcerative Colitis (affecting the colon). Inflammation in the gut causes awful digestive symptoms and increases the risk of developing colorectal cancer.

Some IBD treatments are nonspecific and work toward reducing inflammation through the use of steroids or by reducing overall immune system activity. While some recent IBD treatments, such as therapeutics inhibiting the production of tumor necrosis factor alpha (a protein that drives inflammation), are more specific, they can have unwanted off-target effects on other parts of the body.

So, how can gut bacteria help? As I was researching this, I came across numerous research papers from the past couple of years, like this one on engineering the commensal E. coli Nissle (EcN) 1917 strain to fluoresce upon encountering the inflammatory marker thiosulfate in the intestine and release an immunomodulatory protein to decrease inflammation (Chowdhury et al., 2022). I also stumbled on this paper, which edited the same EcN strain to carry a polymer composed of two gasotransmitters: carbon monoxide (CO) and hydrogen sulfide (H₂S) (Ma et al., 2025). Although these molecules sound toxic, they act as signaling molecules, contributing to the reduction of inflammation. Researchers orally delivered this engineered probiotic to IBD-induced mice, and found localized release of CO and H₂S at inflamed sites; this led to lower inflammation and reshaping of the gut microbiota—ultimately reducing IBD symptoms.

Furthermore, studies have suggested that butyrate, a short chain fatty acid and metabolite secreted by some gut microbiota strains, induces apoptosis (programmed cell death) in cancer cells (Zhao et al., 2024).

Challenges & Looking Ahead

These research advances certainly hold promise, but turning them into therapeutics brings some problems. The digestive tract—especially the stomach—is harsh, so having engineered bacteria effectively reach the gut and multiply there is a challenge (potentially reducing therapeutic efficacy).

Additionally, colon cancer is an incredibly complex disease with multiple subtypes—meaning there’s no one-size-fits-all treatment—and effectively delivering therapeutics to tumors remains a challenge. Manufacturing these “bacterial therapeutics” (in a similar way that traditional small molecule therapeutics are produced) would be more expensive, hindering scalability.

Currently, engineered gut bacteria are in the research stage, and it’ll likely be a long time before any of this enters clinical trials or gets approved by the FDA. While no one knows what this process looks like, as a student, I’m always asking what if?—because if we don’t, we would never know what’s possible.

References

Chen, C. et al. (2024). Biological resilience and gut microbiome signatures. Nature Mental Health. https://www.nature.com/articles/s44220-024-00266-6

Chowdhury, S. et al. (2022). Biomarker-responsive engineered probiotic diagnoses, records, and ameliorates inflammatory bowel disease in mice. Cell Host & Microbe. https://www.sciencedirect.com/science/article/pii/S1931312822005765

Godoy, M. (2024). Your gut microbes may shape your stress response. NPR. https://www.npr.org/sections/shots-health-news/2024/06/24/nx-s1-5018044/gut-microbiome-microbes-mental-health-stress

Ma, Q. et al. (2025). Engineered probiotic with CO/H₂S polymers reduces gut inflammation in mice. Angewandte Chemie. https://onlinelibrary.wiley.com/doi/full/10.1002/anie.202502588

Zhang, L. et al. (2025). Update on the gut microbiome in health and diseases. PMC. https://pmc.ncbi.nlm.nih.gov/articles/PMC10989414/

Zhao, Y. et al. (2024). Butyrate and colorectal cancer: Mechanisms and clinical translation. PMC. https://pmc.ncbi.nlm.nih.gov/articles/PMC10919761/

Zhou, W. et al. (2024). Characterizing the human gut microbiota across populations. Nature Communications Biology. https://www.nature.com/articles/s41522-024-00580-y