Gut Microbe Byproducts Boost Metabolism-Regulating Cells
New research identifies a pathway to potentially combat obesity’s metabolic effects.
Scientists have discovered that byproducts from gut bacteria may offer a new therapeutic approach for metabolic issues linked to obesity. The research centers on restoring crucial hormone-producing cells within the intestine.
Restoring Gut Hormone Production
The study, published in the *International Journal of Molecular Sciences*, highlights enteroendocrine cells (EECs). These specialized intestinal cells are vital for metabolic control, releasing hormones like GLP-1, which aids insulin secretion and appetite suppression. Obesity is known to reduce the number and function of these essential cells, contributing to insulin resistance.
Researchers explored how indole, a metabolite derived from dietary tryptophan (an amino acid in protein-rich foods), could help regenerate EECs. Using “mini-gut” organoids and rat models, they found that obesity caused a roughly 60% decrease in these hormone-producing cells.
Intriguingly, treating human gut organoids with indole or a probiotic’s growth medium significantly increased EECs, more than doubling their numbers. This effect was dependent on a cell receptor known as the aryl hydrocarbon receptor (AhR), indicating its key role in the process.
“Our findings suggest that microbial metabolites derived from dietary tryptophan can reverse obesity-associated reductions in hormone-secreting gut cells. This points to a potential therapeutic strategy that leverages the gut microbes to improve metabolic outcomes in obesity.”
—Alip Borthakur, Ph.D., Assistant Professor of Biomedical Sciences at Marshall University Joan C. Edwards School of Medicine
This research provides foundational evidence for developing interventions targeting the gut microbiota. Such strategies, including probiotics or dietary changes, could enhance incretin hormone production, thereby improving glucose metabolism and appetite regulation in individuals with obesity.
Student Collaboration and Future Potential
The study benefited from the work of several students, including undergraduate Morrison Chicko and graduate students James Hart and Hassan Mansour, as well as doctoral student Harshal Sawant. Faculty members Subha Arthur, Ph.D., and Jennifer Haynes, Ph.D., also contributed.
“It has been exciting to mentor four enthusiastic, intelligent, curious and dedicated Marshall students at different times of the study,” stated Borthakur. “They were thrilled to use the ‘mini gut’ model, a 3D human intestinal organoid model that truly represents the architecture and compositional complexity of the native human gut.”
The study received support from the National Institutes of Health through grants from the National Institute of Allergy and Infectious Diseases (NIAID) and the National Institute of General Medical Sciences (NIGMS).
The potential for gut microbiome modulation in treating metabolic disorders is significant. For example, studies have shown that interventions like fecal microbiota transplantation can improve insulin sensitivity in individuals with metabolic syndrome (Source: Frontiers in Endocrinology, 2023).