A new generation probiotic candidate targeting obesity identified


Scientists from the Catholic University of Louvain report that Dysosmobacter welbionisJ115Tis found in up to 70% of the healthy population, and this lower abundance correlates with higher BMI, fasting glucose levels, and higher HbA1c (glycated hemoglobin, a marker for the presence of of excess glucose in the blood) in obese people.

With these observations in mind, the researchers then supplemented high-fat diet lab mice with live foods. D. welbionisJ115Tand found that the bacteria partially protected these animals from metabolic disturbances and inflammation.

D. welbionis J115Tis a newly isolated human bacterium, very widespread in the general population and inversely associated with BMI, fasting blood sugar and HbA1c in overweight or obese subjects suffering from a metabolic syndrome ”, write the researchers in the journal Gut.

“The daily administration of life D. welbionis J115Tin mice for at least 6 weeks and up to 13 weeks blunted the metabolic disturbances induced by a high fat diet, by mechanisms independent of specific changes in the gut microbiota, but rather acting on the metabolism of white and brown adipose tissue.

Discovery

The link between the gut microbiota and obesity was first reported by Jeffrey Gordon and his group at Washington University in St. Louis, who found that microbial populations in the gut were different between people. obese and lean people, and when obese people lost weight, their microflora returned to that seen in a lean person. This suggests that obesity has a microbial component (Nature, Vol. 444, pages 1022-1023, 1027-1031).

A 2013 article in Science(Vol. 341, No. 6150), also led by Professor Gordon, found that transplantation of gut bacteria from obese humans into germ-free mice resulted in greater weight gain and fat accumulation than mice given bacteria from the intestines of lean humans.

This has led many research groups to explore whether probiotics can help with weight management. A probiotic is defined as a “Living micro-organisms which, when administered in adequate amounts, confer a health benefit on the host”– FAO / WHO.

However, as the Leuven researchers noted, the vast majority of bacteria linked to obesity (positively or negatively) have never been cultivated.

The team, led by Professor Patrice Cani, first reported the discovery of D. welbionisJ115TIn 2020 in an article in International Journal of Systematic and Evolutionary Microbiology, Noting at the time that the bacterium is closely related to a species called Oscillospira Guillermondiiwhich has been constantly linked to thinness. However, O. Guillermondiihas not yet been cultivated.

Study details

For the new study, the researchers tested the presence and abundance of D. welbionisJ115Tin nearly 12,000 people at the Human Microbiome Project, the American Gut Project, the Flemish Gut Flora Project and Microbes4U.

This revealed that D. welbionisJ115Thas been detected in between 63% and 70% of the healthy population, and was negatively associated with BMI, fasting blood sugar, and HbA1c in obese people with metabolic syndrome.

Professor Cani and his colleagues were able to cultivate D. welbionisJ115Tand supplement the mice fed a high fat diet. Laboratory animals were given supplements of live bacteria, live but frozen bacteria, or dead bacteria (pasteurized).

The results indicated that both live forms of the bacteria reduced body weight and body fat gains in mice, but pasteurization “Completely abolished its beneficial effects”.

“We also found that the living bacteria were unable to permanently colonize the gastrointestinal tract of mice”,write the researchers. “Indeed, after 72 hours of wash-out, the fecal content of D. welbionis J115Twas below the qPCR detection limit.

“That the beneficial effects of D. welbionis J115Tare mediated by constituent components or metabolites present in both the fresh and frozen preparation, but not by the metabolites produced in the gut, warrants further investigation.

“Overall, this study provides proof of concept that the correlation observed in obese humans is fully supported by experiments in mice showing beneficial effects of D. welbionis J115T.”

“Over time, this genus and others will form the basis of new probiotic strains and prebiotic targets.”

Commenting independently on the research and its implications, Glenn Gibson, professor of food microbiology and head of food microbial sciences at the University of Reading in the UK, and a pioneer and world-renowned expert in prebiotics and probiotics, told NutraIngredients-USA : “This work comes from a highly regarded scientific group.

“Research is exploiting new molecular approaches to unravel the diversity of the microbiome”, he added. “Inevitably, this will lead to the discovery of new taxa with beneficial properties. This is the case here, with the discovery of a new producer of butyrate. Over time, these genus and others will form the basis for new strains of probiotics and prebiotic targets. This, of course, assumes that the safety and health promoting properties of the new microbes are confirmed. “

And after? “An incredible scientific opportunity”

These additional studies are already being planned. Professor Cani told NutraIngredients-USA: “The project will continue at the level of laboratory research for basic science and the investigation of other paradigms / diseases (ie nutritional interventions, intestinal inflammation, colon cancer and other cancers / metastases). It is an incredible scientific opportunity for us to continue our work on this fascinating bacterium.

“The WELBIO institute (which partially funded this project, and the bacterium now bears its name: Welbionis) also monitors the valuation of the project at industrial level. This means that the scale-up is fully part of the project and I really want to progress in this direction. Interestingly, the culture medium used is already a medium compatible for human use. We have learned from our past experience with Akkermansia.

“The intellectual property on the use of this new bacterium is currently held by UCLouvain (my university) and we are looking for potential licenses, co-development or any interesting potential collaboration that will help us move from mouse to mouse. human. “

Professor Cani added that it is too early to say when studies of human intervention with D. welbionis J115T will be executed, “but of course I am going strongly in this direction”.

“We must secure funds to carry out the various studies”, added Professor Cani. “But the process is similar to that done with Akkermansia, first solid toxicological studies and hopefully a first administration in human volunteers within the next two years.

UCLouvain has produced a YouTube video explaining the work:

Source: Intestine
Published online ahead of print, June 8, 2021. doi: 10.1136 / gutjnl-2020-32377
Dysosmobacter welbionis is a newly isolated human commensal bacterium that prevents obesity and food-induced metabolic disorders in mice.
Authors: T. Le Roy et al.


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