A study led by the Institute of Agrochemistry and Food Technology (IATA), located in the scientific-academic area of the Science Park of the University of Valencia (PCUV) and Severo Ochoa centre of excellence under the Higher Council for Scientific Research (CSIC), has identified the important role that the human intestinal bacteria Phascolarctobacterium faecium could play in the prevention and treatment of obesity. A strain of this bacterial species, so far little studied, has shown protective properties against obesity and its metabolic complications thanks to its ability to counteract the harmful effects of high-calorie diets on the functioning of the immune system. The finding, published in the journal Nature Microbiology, is supported by the Centre for Integrative Biology (CIBIO) of the University of Trento (Italy).
The work has combined an analysis of more than 7,500 human microbiomas with functional experiments in mice. The results of the meta-analysis of the intestinal microbiome, carried out with data from multiple population groups of 15 different nationalities, has shown that the species Phascolarctobacterium faecium is more common in people with healthy weight than in overweight or obese individuals, regardless of age, sex and geographical region. This finding has reinforced the idea that the presence of this bacterium is an indicator of good metabolic health.
"We have identified a microbial biomarker associated with healthy weight that remains constant in very diverse populations. The absence of this bacterium could be used as an early marker of obesity risk," says IATA researcher and study coordinator Yolanda Sanz.
The results show that administration of Phascolarctobacterium faecium (DSM strain 32890) to mice with obesity induced by a high-calorie diet significantly reduced weight gain, adiposity, intestinal and systemic inflammation and glucose intolerance. Specifically, the bacteria decreased body weight by 25%, accumulated fat by 35% and improved glucose tolerance with effects comparable to those of semaglutide, used in the treatment of type 2 diabetes to regulate appetite and blood sugar levels.
A key finding of the study is that this strain has beneficial effects on metabolism through its ability to modulate innate immune system function, even when inactivated by pasteurization. This bacterium reprograms the inborn immune system cell phenotype, reducing the presence of pro-inflammatory macrophages and favoring the activation of alternative macrophages, that block the cascade of inflammatory events occurring in the intestine against the background of obesity.
This change also reduces the presence of other inflammatory immune cells (known as ILC1) in the intestine, which are often elevated in people with obesity and stimulate the production of inflammatory substances such as interferon gamma, that alters the intestinal barrier function and causes metabolic disturbances. These effects appear to depend on structural components of the bacterial cell of P. faecium, such as proteins or fragments of its cell wall, capable of activating specific immune receptors (called Toll-like receptor 2 or TLR2) present in innate immune cells.
"These results demonstrate that it is possible to redirect the immune response against diet, blocking the sequence of inflammatory events by the action of a bacterium on the intestine. This, in turn, restores the functioning of other organs involved in the regulation of metabolism, which is an encouraging finding for the development of new strategies to combat metabolic diseases more effectively." Yolanda Sanz, IATA researcher and study coordinator
"By reprogramming the phenotype and inflammatory function of macrophages, the immune balance in the intestine is restored, which allows to curb chronic inflammation caused by high-calorie diets and thus improve the overall metabolic health of the organism.", adds Rebeca Liébana, researcher at IATA-CSIC who contributed to the study during her doctoral thesis.
This finding not only expands knowledge about the complex interactions between diet, immunity and microbiota (the microorganisms living in our body), but it opens up new possibilities to develop therapies aimed at preventing or treating obesity with alternative or complementary mechanisms of action. "These results demonstrate that it is possible to redirect the immune response against diet, blocking the sequence of inflammatory events by the action of a bacterium on the intestine. This, in turn, restores the functioning of other organs involved in the regulation of metabolism, which is an encouraging finding for the development of new strategies to combat metabolic diseases more effectively," says Yolanda Sanz.
Although the study has been conducted in mice, the authors highlight its relevance as a starting point for future human clinical trials. Their approach is part of an increasingly promising line of research: microbiota modulation-based therapies, which open up new possibilities for designing more personalized interventions that complement conventional pharmacological treatments.
Source: CSIC Delegation Comunitat Valenciana