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Post-surgery microbiome investigated

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Health Canada (Commonwealth Union) – University of Toronto and Partner Hospitals research study reveals alterations in gut microbiota following bariatric surgery can directly enhance metabolism, irrespective of factors such as food intake, weight loss, and other metabolic variables.

Their ongoing investigations, including a study published in the journal Cell Reports Medicine last year, focused on post-surgery patients and indicate that microbiome-based interventions like probiotics and fecal matter transplants hold promise for improving metabolic health. This research suggests a potential future role in reducing the necessity for weight-loss surgery itself.

According to Johane Allard, a clinician-scientist at University Health Network and a professor at U of T’s Temerty Faculty of Medicine, understanding the contribution of the microbiome to metabolic improvements post-bariatric surgery has been limited until now. The study demonstrates that, even with no other changes, the modified microbiome independently influences positive outcomes, offering insights into potential mechanisms.

Researchers of the study pointed out that Bariatric surgery is a key treatment for severe obesity, altering the digestive system’s size and structure to restrict food intake and nutrient absorption. However, it carries health risks and considerable costs to healthcare systems, exceeding $20,000 per procedure in Canada. The surgery releases gut hormones that enhance insulin sensitivity and decrease appetite, also causing unexpected changes in gut microbiota composition and function. This complexity has led researchers to explore the biochemical alterations contributing to metabolic improvements and weight loss, aiming to develop novel treatments. However, the vast variability in individual gut microbiota has posed challenges in identifying broadly effective microbiota-related therapies.

The recent preclinical investigation addresses this challenge by utilizing paired fecal matter transplants. The research team in Toronto conducted a transfer of fecal matter from four individuals to mice, both before and after the participants underwent bariatric surgery. Both groups of mice were fed an identical high-fat, western diet in a sterile environment, and the outcomes were observed over several weeks.

Mice that received the fecal transplant after surgery exhibited significantly enhanced blood sugar control and insulin sensitivity compared to those receiving the transplant before surgery. This suggests a substantial influence of the microbiome on improved metabolism, independent of any changes in body weight. Notably, the human participants in the study also displayed increased insulin sensitivity and weight loss, aligning with expectations.

Surprisingly, there was an observed rise in mass and energy expenditure in brown fat among mice that underwent the post-surgery fecal transplant, revealing unexpected effects on metabolic processes.

“We were very surprised by the data in brown adipose tissue,” added Dana Philpott, who is a co-principal investigator of the study as well as professor of immunology at Temerty Medicine. “We thought if we looked at regular [white fat] adipose tissue, we might see decreased fat or an ability to metabolize better, but the finding was very specific to brown fat.”

Heat presented early indications that something of interest was occurring in brown fat, which has a part in regulating the temperature of the body.

“When we first put the post-surgery transplant mice in the metabolic cages, we noticed they generated more heat,” added Jitender Yadav, who is a postdoctoral researcher in the Philpott lab as well as a co-first author on the study. “We also noticed in some of the literature that bariatric surgery in mice increases brown adipose tissue and energy expenditure, and in our study, we were able to see the similar effect just by transferring the post-surgery microbiome.”

Additionally, the research team identified biochemical and transcriptional indicators pointing towards diminished inflammation in the white fat of mice that underwent post-surgery fecal transplants, indicating further enhancements in metabolic health. To investigate potential microbiota-related alterations accounting for these metabolic improvements, the researchers examined and compared metabolites in stool samples obtained from mice before and after surgery.

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