New research from Marshall University suggests that certain byproducts made by gut bacteria may help reverse a hidden cause of obesity-related metabolic dysfunction: the loss of hormone-producing cells in the gut.
Published July 23 in the International Journal of Molecular Sciences, the study shows that tryptophan-derived compounds like indole can more than double the number of these specialized cells in lab-grown human intestinal tissue, pointing to a potential new way to treat insulin resistance and poor appetite control.
How Gut Hormones Influence Metabolism
Enteroendocrine cells (EECs) are a small but powerful group of hormone-secreting cells in the lining of the gut. One of their most important products is glucagon-like peptide-1 (GLP-1), which helps the body release insulin and feel full after eating. But in people with obesity, these cells decline—by as much as 60% in rats fed a high-fat diet, according to the new study. This loss may worsen blood sugar regulation and appetite control.
“Our findings suggest that microbial metabolites derived from dietary tryptophan can reverse obesity-associated reductions in hormone-secreting gut cells,” said Dr. Alip Borthakur, principal investigator and corresponding author.
The Role of Tryptophan and Indole
Tryptophan is an amino acid found in protein-rich foods like meat, dairy, and legumes. When certain gut microbes, such as Lactobacillus acidophilus, digest tryptophan, they produce metabolites like indole. These compounds activate a protein in human cells called the aryl hydrocarbon receptor (AhR), which has emerged as a key player in gut health and immunity.
To test whether these microbial byproducts influence EEC development, the researchers used human colon organoids—tiny, lab-grown “mini-guts”—and treated them with either pure indole or the supernatant from tryptophan-fed probiotic cultures. Both treatments caused a more than twofold increase in the levels of chromogranin A, a marker of EECs. Blocking AhR with a chemical inhibitor erased this effect.
Key Findings
- Obese rats had ~60% fewer EECs and lower levels of GLP-1 than control rats.
- Tryptophan-derived indole increased EEC markers in human gut organoids.
- Probiotic supernatants from tryptophan-fed Lactobacillus enhanced EEC growth.
- All observed effects depended on activation of the aryl hydrocarbon receptor (AhR).
Therapeutic Implications
Drugs that mimic GLP-1, such as semaglutide, have already transformed obesity care. But they come with side effects and are costly. This new research suggests an alternative: restoring the body’s own ability to produce GLP-1 through diet or targeted probiotics. “This points to a potential therapeutic strategy that leverages the gut microbes to improve metabolic outcomes in obesity,” said Borthakur.
The team notes that indole and other microbial metabolites may fine-tune gut cell development through AhR, possibly shifting stem cells toward hormone-producing lineages. While more research is needed—especially using samples from patients with obesity—the work lays a foundation for future microbiome-targeted therapies.
Looking Ahead
“It has been exciting to mentor four enthusiastic, intelligent, curious and dedicated Marshall students at different times of the study,” Borthakur said. He praised their work using the complex organoid model, which closely mimics the architecture of the human gut. Their findings may one day shape how we treat obesity—not just by blocking appetite, but by rebuilding the gut’s own hormone factory, cell by cell.
Journal: International Journal of Molecular Sciences
DOI: 10.3390/ijms26157080
Article Title: Gut Microbial Metabolites of Tryptophan Augment Enteroendocrine Cell Differentiation in Human Colonic Organoids
Publication Date: July 23, 2025
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