Researchers at the University of Toronto, in collaboration with partner hospitals, are unveiling groundbreaking insights into how gut microbiota changes following bariatric surgery can independently improve metabolism.
Their findings, published in Cell Reports Medicine, highlight the profound impact of these microbiota changes, separate from factors like food intake, weight loss, or other metabolic variables.
This ongoing research is pivotal, particularly for patients who have undergone bariatric surgery, a major treatment option for severe obesity.
The surgery modifies the digestive system to limit food intake and nutrient absorption and has been known to release gut hormones that improve insulin sensitivity and reduce appetite.
A surprising outcome of the surgery, however, has been alterations in the gut microbiota, whose role in post-surgical metabolic improvements has been unclear until now.
The study conducted by the Toronto team, including Johane Allard, a clinician-scientist at University Health Network and professor at U of T’s Temerty Faculty of Medicine, used a novel approach to explore these changes.
They transferred fecal matter from human patients to mice, both before and after the patients underwent bariatric surgery.
This method allowed the researchers to control for diet and environment, isolating the impact of the microbiota changes.
The results were striking. Mice that received the post-surgery microbiota exhibited significantly better blood sugar control and insulin sensitivity than those with pre-surgery microbiota, despite no changes in body weight. This indicated a direct role of the altered gut microbiota in metabolic improvements.
Furthermore, the study revealed an increase in brown fat mass and energy expenditure in mice that received the post-surgery microbiota. Brown fat is known for its role in body temperature regulation, and this finding was unexpected.
The team, including Dana Philpott, a co-principal investigator and professor of immunology at Temerty Medicine, was surprised to see these specific changes in brown fat, rather than in white fat.
In addition to these physical changes, the researchers noted biochemical and transcriptional markers of reduced inflammation in the white fat of the post-surgery mice, signifying improved metabolic health.
They also observed significant changes in metabolites like tryptophan metabolites, short-chain fatty acids, and acylcarnitines in the stool samples from post-surgery mice. These changes in metabolites were consistent, despite variations in the individual microbiota.
This study shifts the focus in microbiome research from the bacterial makeup to the metabolites produced by these bacteria. These metabolites, absorbed downstream, are now seen as key influencers of health.
The researchers believe that therapies targeting these metabolites, such as pre- and probiotics, dietary changes, and fecal matter transplants, could be effective for improving metabolism and aiding weight loss.
Herbert Gaisano, a co-principal investigator and clinician-scientist at Toronto General Hospital Research Institute, plans to further analyze these metabolites in human tissue samples.
The aim is to understand precisely how these metabolites function and contribute to metabolic improvements post-surgery.
This groundbreaking research opens up new possibilities for treating metabolic health issues.
It suggests that microbiome-based therapies could potentially reduce the need for weight-loss surgery in the future, offering a less invasive and more holistic approach to treating obesity and related metabolic disorders.
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The research findings can be found in Cell Reports Medicine.
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