The human gut microbiome still has unknowns collectively described as “the dark matter of the intestine”. They comprise numerous unidentified species, hidden taxa and genes that do not have a match in functional databases. Although the gut microbiome is emerging as a potential target in preventing or treating obesity-related metabolic diseases, only a few gut microbes have been tested in preclinical studies and translation in humans is lacking.

In a new study published in Gut by researchers from UCLouvain, Cliniques universitaires St-Luc and KU Leuven, we can report for the first time a newly isolated commensal bacterium found in 70% of the general population while almost absent in people with obesity and diabetes.

The newly discovered gut bacterium Dysosmobacter welbionis was first isolated in 2017 from the gut of one healthy subject. It is a newly cultivated strain of the Ruminococcaceae family and is closely related to another gut bacteria correlated with leanness and health such as the unculturable Oscillospira guillermondii.

 

But how did the story start?

The story of the discovery of D. welbionis started when the team repeatedly observed that a bacterium called Subdoligranulum was always evolving in the same direction than the beneficial bacterium Akkermansia muciniphila. So, they decided to take a closer look at this genus of bacteria and they tested the unique cultured species from this genus called Subdoligranulum variabile.

Although the abundance of Subdoligranulum was correlated positively with HDL-cholesterol levels and negatively correlated with fat mass and inflammatory markers in humans, it did not improve hallmarks of obesity and diabetes in mice. That led the team to try to isolate a new strain of Subdoligranulum to better elucidate if the lack of effects observed in mice were due to the strain used of S. variabile, and if eventually another newly isolated Subdoligranulum would improve metabolic health.

After 2 years of work, the scientists isolated and cultivated nearly 600 bacteria from the intestine, but they never succeed to isolate any Subdoligranulum. Instead, they uncovered a new genus of bacterium that is Dysosmobacter, and the species welbionis.

 

Protective effects of D. welbionis against obesity and obesity-related features

Based on data from the Human Microbiome Project, American Gut Project, Flemish Gut Flora Project and Microbes4U, they found that D. welbionis abundance was present in up to 70% of the general population. Furthermore, its absolute abundance in the fecal microbiota of people with obesity suffering from metabolic syndrome was inversely correlated with body mass index, fasting glucose and glycated hemoglobin, which is used to determine how well a person with diabetes has been managing their blood sugar over the previous months.

Supplementing mice fed a high-fat diet with live D. welbionis strain J115T (1.0 x 109 of the freshly cultured or the cryopreserved  bacterium from 6 to 13 weeks) reduced body weight and fat mass gain in a time-dependent manner. However, pasteurizing the bacterium abolished its beneficial metabolic effects. The live bacterium was unable to permanently colonize the mice’s gastrointestinal tract, which highlights that durable colonization of the gut is not a requisite for health effects from probiotics.

The diet-induced obesity-related protective effects provided by D. welbionis were accompanied by improved glucose homeostasis, lower insulin resistance and reduced subcutaneous and mesenteric white adipose tissue hypertrophy and genes related to inflammation, coupled with a higher number of genes involved in fatty acid mobilization and higher mitochondria number in the brown adipose tissue. The findings show that the beneficial metabolic effects of D. welbionis J115T are partly mediated by the innate immune system and involve the recovery of brown adipose tissue metabolism and activity.

In conclusion, these findings suggest the potential of butyrate-producing bacteria such as D. welbionis J115T as a next-generation probiotic candidate for managing obesity and diabetes. Beyond the correlation findings linking D. welbionis to better obesity-related outcomes, the team was able to confirm the metabolic effects of the bacterium in mice. The next step as a team is to test if D. welbionis has benefits for people with non-communicable diseases, including obesity and type 2 diabetes.

 

See the video explaining findings’ relevance:





 

 

References:

Van Hul M, Le Roy, Prifti E, et al. From correlation to causality: the case of Subdoligranulum. Gut Microbes. 2020; 12(1):1-13. doi: 10.1080/19490976.2020.1849998.

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. 2021. doi: 10.1136/gutjnl-2020-323778.