Dysosmobacter welbionis as potential promising next-generation probiotic for improving metabolic health?

Dysosmobacter welbionis J115^T is a butyrate-producing commensal bacterium isolated from the human gut in 2017 that has been detected in about 70% of the general population, in a similar amount to Akkermansia muciniphila. Previous research revealed that D. welbionis was associated with lower body mass index, fasting glucose, and improved glycemic control in patients with obesity and type 2 diabetes. While preliminary findings showed treatment with D. welbionis J115^T leads to lower weight and fat mass gain and improved glucose metabolism in high-fat diet-fed mice, little is known about how this newly identified bacterium improves metabolic health.

Recent in vitro findings showed for the first time that D. welbionis J115^T produces bioactive lipids (e.g., 12,13-DiHOME and C18-3OH) that have anti-inflammatory properties and act on energy metabolism by increasing brown adipose tissue activity. Interestingly, D. welbionis produces 19 bioactive lipids with up to 60 times higher levels than Escherichia coli Nissle 1917, a known probiotic with anti-inflammatory properties mediated by bioactive lipids with potential benefits for ulcerative colitis.

In addition, the beneficial effects observed in the culture medium were linked to the abolishment of whitening of the brown adipose tissue and changes in bioactive lipids with PPAR agonist properties in the brown adipose tissue, the colon, and the blood of high-fat diet-fed mice supplemented with D. welbionis.

Our research group moved from correlative works to properly investigating these positive effects and their clinical translation. A recent small randomized controlled intervention with the prebiotic inulin showed D. welbionis was highly abundant in the fecal samples of metformin-treated individuals with obesity and diabetes and correlated negatively with aspartate aminotransferase, alanine aminotransferase and fasted blood glucose levels.

We also compared the effects of D. welbionis J115^T supplementation vs metformin administration on glucose intolerance and fat mass in mice on a high-fat diet. D. welbionis J115^T improved glucose tolerance to a better extent than metformin and reduced fasted glycaemia by mechanisms independent of glucagon levels and key liver gluconeogenic enzymes in high-fat diet-fed mice and independently of fat mass.

Participants who responded to the prebiotic by decreasing their body mass index had almost three times higher levels of D. welbionis at baseline. These results highlight the variability of individuals in the response to gut microbiome-targeted interventions, with habitual diet being a significant factor shaping the efficacy of a prebiotic. This difference between responders and non-responders was more pronounced when comparing individuals treated with metformin vs those not treated with metformin in line with previous findings supporting positive changes in the gut microbiota composition behind this drug’s efficacy. Altogether, these proof-of-concept findings investigated the impact of D. welbionis administration in vivo and suggested a potential role of enriching the gut microbiome with this novel gut bacterium as a therapeutic adjuvant in the context of cardiometabolic disorders.

As a matter of fact, a recent paper published in April 2024 established a mechanistic connection between Dysosmobacter and other Oscillibacter genera and cardiovascular health. By focusing on cholesterol metabolism, they found that D. welbionis J115^T metabolizes cholesterol. Strikingly, the abundance of D. welbionis J115^T and other Oscillibacter spp were associated with decreased fecal and plasma cholesterol levels.

Despite the rapid increase in scientific publications over the last decade on gut microbiota, obesity, and type 2 diabetes mellitus, determining the value of targeting particular gut microbiome-related features for body weight management in clinical practice remains a challenge.

Having said that, together with Akkermansia muciniphila and Anaerobutyricum soehngenii (formerly Eubacterium hallii), D. welbionis emerges as a potential next-generation beneficial bacteria to tackle metabolic disorders and related diseases. While these findings are significant, they must be confirmed in larger cohorts that consider confounding factors. For now, the first treatment for cardiometabolic disorders is a healthy diet and sufficient exercise. 

References:

Le Roy T, Moens de Hase E, Van Hul M, et al. Dysosmobacter welbionis is a newly isolated human commensal bacterium preventing diet-induced obesity and metabolic disorders in mice. Gut. 2022; 71(3):534-543. doi: 10.1136/gutjnl-2020-323778.

Moens de Hase E, Petitfils C, Alhouayek M, et al. Dysosmobacter welbionis effects on glucose, lipid, and energy metabolism are associated with specific bioactive lipids. J Lipid Res. 2023; 64(10):100437. doi: 10.1016/j.jlr.2023.100437.

Moens de Hase E, Neyrinck AM, Rodriguez J, et al. Impact of metformin and Dysosmobacter welbionis on diet-induced obesity and diabetes: from clinical observation to preclinical intervention. Diabetologia. 2024; 67(2):333-345. doi: 10.1007/s00125-023-06032-0.

Petakh P, Kamyshna I, Kamyshnyi A. Effects of metformin on the gut microbiota: A systematic review. Mol Metab. 2023; 77:101805. doi: 10.1016/j.molmet.2023.101805.

Li C, Strazar M, Mohamed AMT, et al. Gut microbiome and metabolome profiling in Framingham heart study reveals cholesterol-metabolizing bacteria. Cell. 2024; 187(8):1834-1852.e19. doi: 10.1016/j.cell.2024.03.014.

Cani PD, Van Hul M. Gut microbiota in overweight and obesity: crosstalk with adipose tissue. Nat Rev Gastroenterol Hepatol. 2024; 21(3):164-183. doi: 10.1038/s41575-023-00867.