US study uncovers key gut metabolite’s role in combating obesity
Vanderbilt University researchers have made a groundbreaking discovery about the role of gut microbiota in obesity prevention. Published in the journal Cell Host & Microbe, their study reveals that bacteria in the small intestines produce a compound crucial for guarding against obesity. This finding sheds light on how disruptions in the microbiota, such as those caused by early-life antibiotic exposure, can increase childhood obesity risks.
One of the study’s key insights is the potential for probiotic bacteria, or the compounds they produce, to serve as preventive measures against antibiotic-associated childhood obesity. “Previous studies have indicated that either antibiotics or a high-fat diet can lead to obesity later in life by disturbing the microbiota,” explained Mariana Byndloss, DVM, PhD, assistant professor of Pathology, Microbiology and Immunology at Vanderbilt. “Our aim was to investigate the combined effect of these risk factors, which children often face simultaneously.”
Under the guidance of graduate student Catherine Shelton, who is the first author of the paper, the research team developed a model using young mice exposed both to antibiotics and a high-fat diet. This dual exposure led to increased weight gain, adiposity, and metabolic dysfunction in the mice.
The team’s investigation pinpointed a disruption in the small intestine microbiota caused by the combination of antibiotics and a high-fat diet. This disruption led to decreased levels of beneficial Lactobacillus bacteria and a corresponding reduction in a metabolite they produce, known as phenyllactic acid. The researchers identified phenyllactic acid as a regulator of a fat metabolism pathway in intestinal epithelial cells — the cells lining the intestines.
Byndloss noted, “The absence of this specific microbe and its metabolite changes how intestinal epithelial cells process fat, leading to increased fat in the bloodstream. Normally, phenyllactic acid instructs these cells to limit fat packaging and secretion. When this microbial signal is lost, the cells behave differently, resulting in increased obesity in mice.”
This discovery opens up the possibility of using phenyllactic acid or Lactobacillus bacteria as interventions for obesity, particularly in children undergoing antibiotic treatment. Lactobacillus is commonly found in probiotic supplements and in fermented foods like kombucha, kimchi, and probiotic milk products popular in Asia.
“Some cultures already have a practice of giving children fermented milk, which might be inadvertently providing this protective compound,” added Byndloss.
In the study’s mouse model, exposure to antibiotics alone did not lead to weight gain; it was the combination of antibiotics and a high-fat diet that heightened obesity risk. Byndloss suggests a healthy diet with limited excess dietary fats as a way to mitigate the negative impact of antibiotics on the microbiota.
Surprisingly, the researchers found that intestinal epithelial cells play a significant role in weight gain. “We usually associate obesity with adipose tissue and the liver, not intestinal cells. It was unexpected that a single metabolite acting on these cells could have such a profound effect in preventing weight gain,” Byndloss remarked.
Ongoing studies by Byndloss and her colleagues are exploring the role of Lactobacillus and phenyllactic acid in early life, particularly during breastfeeding. Given the high fat content in breast milk, the team is investigating whether this pathway offers protective benefits against obesity from a very early age.