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Ask not “what your gut microbiome can do for you”, but “what you can do for your gut microbiome”

Defined health outcomes are increasingly being linked to prebiotic ingredients and supplements. For example, mounting evidence recently led the FDA to issue a qualified health claim regarding the ability of digestion resistant starch to reduce the risk of type 2 diabetes. With the direct annual cost of diabetes recently estimated to be $825B (1), the potential application of prebiotics to reduce disease risk is appealing from both health care and business investment perspectives.

The mechanisms by which prebiotics exert various health benefits continue to be elucidated, but the link between prebiotics and improved glycemic response has been relatively well-studied. Given that prebiotics, by definition, are undigested by the body’s enzymes, the consumption of prebiotics contributes to our sense of fullness without causing an increase in blood glucose levels.

One aspect of the blood glucose lowering abilities of prebiotics is due to the fermentation of prebiotics by various microorganisms in the gut. While we tend to think of fermentation as being a simple process, prebiotic fermentation in the gut is a multi-step process.

Ruminoccus bromii has been shown to be pivotal in initiation of digestion resistant starch granule degradation (2). In our previous study (3), Bifidobacterium. ruminatum, Bifidobacterium bifidum and Bifidobacterium pseudocatenulatum were significantly increased in mid-age and elderly adults, likely because these Bifodobacteria preferentially ferment digestion resistant starches like MSPrebiotic® into lactic acid that can then be used as a substrate by butyrate-producing bacteria, including those of the Firmicutes phylum. Alternatively, some gut bacteria may produce butyrate directly from oligosaccharides, as is the case with bacteria belonging to the genus Roseburia (4).

Regardless of the production method, butyrate produced via prebiotic fermentation in the colon plays a number of important physiological roles. First, as a weak acid, butyrate helps to modulate the pH of the colonic environment to favor growth of healthy bacteria while inhibiting the growth of harmful pathogens, including Escherichia coli. Secondly, butyrate provides an important energy source for the colonocytes lining the large intestine. These cells favour butyrate to glucose – contrary to most other cells in the body – and butyrate is estimated to supply up to as much as 10% of the body’s energy demands.

Perhaps most importantly, butyrate acts as a signalling molecule that influences human metabolism. Embedded within the colonic epithelium lie multiple different cell types, including enteroendocrine cells. Also known as L-cells, these cells secrete several hormones, including glucagon-like peptide-1 (GLP-1). GLP-1 is an incretin, a type of hormone that acts to improve insulin secretion by the pancreas in response to elevated blood glucose. GLP-1 also acts on other systems, including the nervous system via the vagus nerve to promote satiety. Importantly, butyrate produced during prebiotic fermentation acts on L-cells in the gut to help induce GLP-1 secretion (5).

How does this help lower blood glucose levels? GLP-1 helps the body to better respond to rising blood glucose levels by instructing the pancreas to secrete more insulin. This mechanism has been demonstrated in animal models of type 2 diabetes, where prebiotic consumption has led to improved GLP-1 secretion and lower blood glucose (6). Furthermore, injectable GLP-1 analogues (Liraglutide) have been developed and are now being prescribed to patients with or at risk of developing type 2 diabetes (7). These drugs appear to provide an effective strategy for improving insulin resistance.

Our most recent study data demonstrated that consumption of MSPrebiotic® resulted in a significant reduction in glucose and insulin resistance in elderly adults. Moving forward, it is logical to pursue interventions that enhance the endogenous GLP-1 secretion given the important role of this hormone. As mentioned previously, the gut microbiome is remarkably accessible and amenable to such interventions and the discovery that prebiotic supplementation alone can stimulate the gut microbiome to increase butyrate levels, as well as reduce glucose and insulin resistance, makes this strategy a promising approach.

As awareness and experience with prebiotic supplements grows in the clinical setting, they may be utilised as a tool to help manage patients with ‘pre-diabetes’, where fasting blood glucose levels trend high but are still below 7.0 mmol/L. Prebiotics offer a cost-effective alternative during early stages of intervention in the course of diabetic disease that could delay or even prevent the need for pharmaceuticals.

Michelle Alfa260

 

Michelle Alfa is the CEO of AlfaMed Consulting. At the recent Probiotics Congress in San Diego, Michelle presented the benefits of digestion-resistant starch in middle aged and elderly adults.


See more blogs on prebiotics.

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