Could increasing delivery of propionate to the human colon be a potential way of improving glucose homeostasis in overweight or obese individuals?

Genes from the gut microbiota encode for a wide range of metabolic activities that allow commensal microbes to ferment dietary fibers and prebiotics into metabolites that include short chain fatty acids (SCFAs). Of these, propionate has been shown to trigger the secretion of gut peptides that take part in regulating appetite and glucose metabolism and reducing inflammation. Although colonic propionate is a potential target to mitigate metabolic disorders associated with obesity, its mechanisms of action have not been elucidated.

A new study, led by Prof. Gary Frost from Imperial College London (United Kingdom), has found that fermentation of inulin in the colon may contribute to the beneficial effects observed on glucose metabolism and inflammation in overweight and obese subjects.

This research has its roots in a previous randomized controlled 24-week study led by Chambers and colleagues that targeted delivery of propionate to the colon through oral inulin-propionate ester (IPE) versus control inulin. That led to improved glucose homeostasis and reduced body weight gain in overweight adults.

However, as Patrice Cani, who is not involved in the study, notes in a commentary: “one of the major caveats in this seminal study was the lack of evidence that the observed effects were due to the presence of inulin itself on IPE or the delivery of propionate into the colon.”

In order to disentangle the underlying mechanisms, in the new study with a randomized cross-over design, the authors compared the dietary supplementation with 20 g/day IPE versus inulin (positive control) and a low-fermentable fiber cellulose (negative control) in 12 overweight or obese adults. After a 42-day period, the intervention effects on the gut microbiota, plasma metabolome and inflammation were measured.

Both IPE and inulin led to a similar improvement in glucose homeostasis parameters—including homeostatic model assessment 2-insulin resistance, insulin sensitivity index, adipose tissue insulin resistance and fasting insulin—that was superior to cellulose. These results suggest that inulin fermentation is enough to improve glucose homeostasis and targeted delivery of propionate to the human colon is not indispensable.

In addition, compared with the low-fermentable fiber cellulose, the observed improvements in glucose homeostasis secondary to IPE and inulin supplementation were not related to differences in body weight, food intake, physical activity or gastrointestinal side effects.

In contrast, IPE and inulin led to different effects on gut microbiota composition and immune parameters.

Changes in gut microbial communities at both the class level (increased Actinobacteria and decreased Clostridia) and order levels (decreased Clostridiales) were found secondary to inulin supplementation when compared with cellulose. In contrast, IPE supplementation only caused changes in gut microbiota composition at the species level compared with cellulose.

Supplementation with IPE was accompanied by a reduction in circulating pro-inflammatory interleukin (IL)-8. These findings were also confirmed in vitro as propionate reduced the secretion of IL-8 by peripheral blood mononuclear cells isolated from healthy humans. Besides this, the researchers also found a small but significant increase in immunoglobulin G levels in the participants receiving IPE relative to cellulose. On the other hand, inulin had no effects on the inflammatory parameters under study.

Meanwhile, fasting insulin following 42 days of IPE, inulin and cellulose supplementation was associated with different metabolites, including plasma N-acetyl glycoproteins, glutamine, tyrosine and glycine.

On the whole, these results show that the fermentation of fibers and their metabolites may contribute to improving host insulin sensitivity. In agreement with a previous small clinical trial that manipulated gut microbiota with a complex mix of dietary fibers in patients with diabetes, overall, these results support the benefits of increasing the amount of fermentable dietary fibers ingested to improve metabolic diseases.

 

References:

Chambers ES, Byrne CS, Morrison DJ, et al. Dietary supplementation with inulin-propionate ester or inulin improves insulin sensitivity in adults with overweight and obesity with distinct effects on the gut microbiota, plasma metabolome and systemic inflammatory responses: a randomised cross-over trial. Gut. 2019. doi: 10.1136/gutjnl-2019-318424. [Epub ahead of print 30 Apr 2019].

Cani PD. Is colonic propionate delivery a novel solution to improve metabolism and inflammation in overweight or obese subjects? Gut. 2019. doi: 10.1136/gutjnl-2019-318776.

Andreu Prados
Andreu Prados
Andreu Prados holds a Bachelor of Science Degree in Pharmacy & Human Nutrition and Dietetics. Science writer specialised in gut microbiota and probiotics, working also as lecturer and consultant in nutrition and healthcare. Follow Andreu on Twitter @andreuprados