New Research from The FASEB Journal: Probiotic bacteria regulate gut hormones

Tuesday, March 18, 2025

Two probiotic bacteria commercially available as oral supplements may boost human health by increasing the gene transcription and secretion of hormones in the gut. The study, conducted with organ-like aggregates of human cells called organoids, also revealed hormones that were not previously known to be secreted by gut cells, according to research published in The FASEB Journal. This information could help researchers build a better probiotic or a drug that works like a probiotic.

The human gastrointestinal system contains a wide range of microbes, including the bacterium Limosilactobacillus reuteri. Living probiotic bacteria and yeasts in supplements and foods, including many dairy products, function as “good” microbes that prevent harmful ones from taking over. They can also have direct effects on health, potentially preventing or treating many conditions. Different microbes—and even different strains of the same microbe—can have varied effects on the body. For example, research has shown that L. reuteri 6475 reduces inflammation, helps wounds heal, and improves social behavior in mouse models of autism. L. reuteri 17938, however, can be used to treat cholic and boost digestive health in infants and children. 

The immune system mediates some of these benefits, but Sara Di Rienzi, Robert Britton, and colleagues at Baylor College of Medicine wondered if L. reuteri could also influence cells in the small intestine, where many probiotic bacteria live. Because of the bacterium’s wide-ranging health effects, the team also hypothesized that L. reuteri could be regulating gut hormones. 

In their study, the researchers used small intestine-derived organoids containing an elevated number of enteroendocrine cells, which secrete hormones. They treated these induced organoids with media that either L. reuteri 6475 or 17938 had been grown in, called conditioned media. These solutions contained factors released by the bacteria that could potentially interact with human cells. The team also analyzed how this conditioned media affected uninduced organoids, which contain many enterocytes—cells that absorb nutrients—but very few enteroendocrine cells. 

Conditioned media from both strains increased the transcription of many hormone genes in induced organoids, though L. reuteri 6475-conditioned media had a stronger impact. In addition, numerous hormones, such as serotonin, were secreted by the media-treated organoids. L. reuteri 6475-conditioned media also regulated the transcription of immune genes in induced and uninduced organoids. Interestingly, the researchers found enterocytes in these organoids transcribed vasopressin and luteinizing hormone subunit beta, which are not known to be produced by these cells. “We were surprised that L. reuteri affected hormones that are well described in the brain, but barely or not described at all in the gut,” says Di Rienzi, who is now at Rutgers University. 

Overall, the study reveals how probiotics can have so many varied effects. “People typically think that probiotics only have effects on the gut in terms of reducing diarrhea, constipation, or inflammation, but our results open up a new paradigm for how probiotics could have systemic effects on the whole body,” says Britton.

Funding: U.S. National Library of Medicine, National Institute of Allergy and Infectious Diseases, Weston Family Foundation, BioGaia AB

Read the full article, “Limosilactobacillus reuteri promotes the expression 1 and secretion of enteroendocrine- and enterocyte-derived hormones,” published in The FASEB Journal.