Microbial by-products unlock intestinal hormone healing

New research from Marshall University shows that certain by-products produced by gut bacteria may help reverse the hidden cause of obesity-related metabolic dysfunction: the loss of hormone-producing cells in the gut.

July 23 International Journal of Molecular Sciencestudies have shown that tryptophan-derived compounds such as indole can make more than twice the number of these specialized cells in laboratory-grown human gut tissue, suggesting a potential new approach to treating insulin resistance and poor appetite.

How intestinal hormones affect metabolism

Enteroendocrine cells (EECs) are a group of small but powerful hormone-secreting cells in the intestinal wall. One of their most important products is glucagon-like peptide-1 (GLP-1), which helps the body release insulin and feel full after eating. However, in obese patients, these cells fall – up to 60% of rats fed a high-fat diet. This loss may worsen blood sugar regulation and appetite control.

“Our findings suggest that microbial metabolites derived from dietary tryptophan can reverse the decrease in obesity-related intestinal secretion cells,” said lead investigator and corresponding author Dr. Alip Borthakur.

The effects of tryptophan and indole

Tryptophan is an amino acid found in protein-rich foods, such as meat, dairy products, and legumes. When certain gut microorganisms (e.g. Lactobacillus acidophilusAbstract tryptophan, they produce metabolites such as indole. These compounds activate proteins in human cells called aryl hydrocarbon receptors (AHRs), which have become a key player in gut health and immunity.

To test whether these microbial by-products affect the development of EECs, the researchers used human colon organs (miniature, lab-grown “mini thyroid”) and treated them with pure indole or probiotic cultures fed from tryptophan. Both treatments resulted in more than tripling levels of chromane A, the marker of EEC. Blocking AHR with chemical inhibitors eliminates this effect.

Key Discovery

• Obese rats had about 60% less EEC and lower levels of GLP-1 than control rats.
• Tryptophan-derived indole increases EEC markers in human bowel cancer.
• Probiotic supernatant from tryptophan feeding Lactobacillus EEC growth growth.
• All observed effects depend on activation of the aryl hydrocarbon receptor (AHR).

Therapeutic significance

Drugs that mimic GLP-1, such as semaglutide, have transformed obesity care. But they have side effects and are expensive. The new study proposes an alternative approach: to restore the body’s ability to produce GLP-1 through diet or target probiotics. “This suggests a potential therapeutic strategy that uses gut microorganisms to improve metabolic outcomes in obesity,” Borthakur said.

The team noted that indole and other microbial metabolites may fine-tune the development of intestinal cells through AHR, which may transfer stem cells to hormone-producing lineages. Although more research is needed, especially using samples from obese patients, this work lays the foundation for future targeted microbiome therapies.

Looking to the future

“It was exciting to mentor four enthusiastic, intelligent, curious and dedicated Marshall students at different times of the study,” said Borthakur, who praised their work using a sophisticated organoid model that closely mimics the architecture of the human gut. Their discovery may one day shape how we treat obesity – not only by blocking appetite, but by rebuilding the gut’s own hormone factories (cells).

Magazine: International Journal of Molecular Science
doi: 10.3390/ijms26157080
Article title: Tryptophan-enhanced differentiation of intestinal microbial metabolites in human colon
Publication date: July 23, 2025

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