Probiotics may boost effectiveness of GLP-1 drugs in obesity treatment, study finds

A Korean study has found that probiotic strain Limosilactobacillus fermentum GB102 could enhance GLP-1 receptor agonist (RA) dulaglutide in obesity treatment. 

The study details that although GLP-1 RA treatments are effective for weight loss, when discontinued, weight regain is common. To resolve this issue, the researchers investigated whether anti-obesity probiotic strains could enhance weight loss from GLP-1 drugs and decrease weight regain.

The study was carried out on mice and found that Limosilactobacillus fermentum GB102 improved glycemic control and reduced body weight in mice fed with a high-fat diet.

The metabolic effects were linked to alterations in circulating metabolic hormones, including adipokines — cell-signaling proteins, hormones, and cytokines that regulate energy metabolism, appetite, inflammation, and immune responses.

The probiotic strain produced high levels of succinic acid — a metabolite linked to thermogenic activation. It also increased whole-body energy expenditure in mice fed a high-fat diet and enhanced the conversion of the essential amino acid arginine into ornithine and citrulline.

It also produced glutamine — an amino acid supporting multiple functions such as muscle recovery, digestive health, immune function, and overall cellular function.

When L. fermentum GB102 was combined with dulaglutide, the strain boosted weight loss, preserved muscle mass, and reduced glycemic rebound and weight regain when discontinuing the drug.

“These findings suggest that energy-metabolism-enhancing probiotics such as GB102 may enhance the metabolic effects of GLP-1 RA therapy and help attenuate weight regain after treatment discontinuation,” the authors say.

Metabolic effect

The study, published in Nutrients, stresses that obesity is increasing rapidly on a global scale. Due to causing multiple chronic metabolic diseases such as type 2 diabetes, cardiovascular disease, and increased morbidity, obesity has become a major public health concern.

The L. fermentum GB102 strain reduced the weight regain when discontinuing dulaglutide drugs.As a response, GLP-1 drugs such as semaglutide (Ozempic and Wegovy) and dulaglutide (Trulicity) have increased in popularity. However, studies have confirmed that when discontinuing the medications, most people regain the weight they lost.

The new study found that the L. fermentum GB102 strain reduced the weight regain when discontinuing dulaglutide drugs, as well as maintaining muscle mass, positioning it as a potential solution to this widespread problem.

However, since this study was done on mice, its potential in humans needs to be further investigated.

Choosing probiotic

The researchers screened various anti-obesity probiotics — bacteria that prevent or reduce obesity by influencing fat storage, metabolism, and appetite. They found L. fermentum GB102 to be most effective due to its high production of succinic acid and its metabolites associated with the various amino acids.

The strain was taken from the vaginal microbiota of healthy Korean women before being cultured in Man-Rogosa-Sharpe medium for six hours and produced succinic acid. The vaginal microbiota is a common source for isolating strains with health benefits, especially for gut health and metabolic regulation, according to the study.

“Based on these metabolic features, we investigated whether this probiotic strain could augment the weight-lowering effects of the GLP-1 RA dulaglutide, preserve muscle mass during weight reduction, and mitigate the weight regain and glycemic deterioration typically observed after treatment withdrawal,” reads the study.

“Our findings support the potential use of a microbiota-derived metabolic adjunct approach to possibly improve both the efficacy and durability of GLP-1 RA therapy.”