When gut microbes run low on fiber, they may start eating you

A new study reveals that plant-based diets may affect our gut microbes and overall well-being in unexpected ways. Researchers led by Jenna AbuSalim at Princeton University and Joshua Rabinowitz, director of the Princeton Institute for Precision Medicine & Therapeutics, conducted two groundbreaking studies. Their findings, published in the Proceedings of the National Academy of Sciences and Nature Metabolism, respectively, shed light on how plant fibers and proteins influence the gut microbiome and the production of beneficial and harmful metabolites.

The first study focused on phenol metabolites, compounds produced by gut bacteria when they break down amino acids tyrosine and phenylalanine. These metabolites can have either positive or negative effects on health. Phenylpropionate and hippuric acid, derived from phenylalanine, are associated with gut health and a healthy body weight. In contrast, p-cresol sulfate and phenol sulfate, stemming from tyrosine, have been linked to worse outcomes for cancer patients and systemic toxicity in those with kidney disease.

The researchers discovered that plant-based fibers and proteins, dubbed "indigestible proteins imitating fiber" (Prif), can shift the balance of phenol metabolites from harmful to beneficial. Prif is processed by gut microbes, altering both the composition of the microbiome and the host's metabolism. Prif also decreases the production of harmful phenols while increasing the production of beneficial ones, ultimately promoting metabolic health.

The second study investigated the origins of phenol and indole metabolites, compounds connected to a range of diseases, including inflammatory bowel disease, neurodegenerative disorders, and cancer. Initially, scientists believed that only gut bacteria produced these metabolites. However, the researchers found that mammalian metabolism can also produce many indole and phenol metabolites independently of gut bacteria.

Metabolites such as indole-3-lactate and indole-3-acetate remained high in mice even after antibiotic treatments disrupted the microbiome. These findings challenge the assumption that gut bacteria are solely responsible for the production of these metabolites, suggesting that mammalian metabolism plays a more significant role than previously thought.

This research has important implications for the development of therapies aimed at manipulating the microbiome and its metabolic outputs. By understanding the role of Prif and the sources of phenol and indole metabolites, researchers can design more targeted dietary, probiotic, and medical interventions to improve metabolic health and combat diseases.