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What’s New With Prebiotics?

A prebiotic is defined as “a substrate that is selectively utilised by host microorganisms conferring a health benefit”. This updated consensus definition from the International Scientific Association for Probiotics and Prebiotics expands the application outside the digestive tract.

Note the requirements for selectivity and for a health benefit. In the context of the digestive tract, this means that a prebiotic substrate cannot be absorbed in the small intestine (excludes, e.g., glucose, sucrose, fructose, lactose, or even the proportion of starch that is hydrolysed to produce glucose), and must persist into the colon, where it can deliver health benefits.

Prebiotic Structure Important for Selectivity

The consumption of a prebiotic by microbes in the GI tract is affected by several factors:

  • The chemical structure of the prebiotic, including degree of polymerisation and branching
  • The presence (and location) of specific enzymes within the microbe
  • The presence of transporter systems within the microbe

Enzymes and transporter systems are most prevalent for substrates comprised of 6-carbon subunits (so-called hexoses, or C6 sugars). There are far fewer enzymes and transporters for substrates comprised of 5-carbon subunits (so called pentoses, or C5 sugars). Differences in these enzyme and membrane transport systems are responsible for the selectivity of prebiotics.

The Role of Metabolites

The metabolites produced by digestive tract microbes play a key role in the health benefits associated with prebiotics and probiotics, and also play a role in the health issues when the dietary intake is low in prebiotics. The challenge is to ingest enough of the right foods, supplemented by the right prebiotics, to maintain or improve health.

Short chain fatty acids (SCFAs) are key metabolites produced by many “healthy” bacteria, and play a role in regulating blood glucose levels, cholesterol, and immune markers. They also play a role in cross-feeding of bacteria, thus supporting the broader community. Changes in levels of SCFAs, individually or in total, are often indicative biomarkers of the efficacy of prebiotics and probiotics. Other health benefits associated with the intake of prebiotics include enhanced bioavailability of minerals, promotion of satiety, alleviation of symptoms associated with antibiotic-associated diarrhea, and reduced inflammation.

Recent Scientific Research on Prebiotics

The ever-expanding knowledge of the microbiome and its impact upon health has been supported by a growing suite of clinical trials examining the effect of prebiotics:

  • A recent review (Fernandes et al., 2017) noted that 3 of 6 trials using inulin (10+ g/d) and GOS (6 – 18 g/d) reduced levels of hs-C-reactive protein and endotoxins in obese/overweight subjects, suggesting immune and anti-inflammatory benefits.
  • Parnell et al. (2017) observed a reduction in lipopolysaccharide levels in overweight subjects after consumption of 21 g/d of oligofructose. Alfa et al. (2017) indicated that 30g/d of resistant starch could improve bifidobacteria levels and eliminate dysbiosis associated with proteobacteria in elderly subjects.
  • Yang et al. (2015) provided evidence of a reduction in OGGT 2h insulin response in pre-diabetes patients that consumed 2g/d of XOS over 8 weeks. Miremadi et al. (2016) reported that trials with inulin (9 – 20 g/d) reduced triglyceride levels, but 20 g/d of FOS and 5.5 g/d of GOS did not.
  • A 3-week trial delivering 15g/d of FOS to adults with Crohn’s Disease improved bifidobacteria counts and disease activity scores (Steed et al., 2008).
  • A meta-analysis of clinical trials indicated prebiotic supplementation could improve satiety, and reduce post-prandial glucose and insulin (Kellow et al., 2014).
  • Williams et al. (2016) observed that 5.5 g/d of GOS could alleviate airway inflammation in subjects with asthma.
Understanding Prebiotic Differences & Selectivity

These clinical trial results, while demonstrating the promise of prebiotic intervention to improve health, also indicate material differences between prebiotics. Clearly, prebiotics are not all the same – they feed different microbes, may generate different metabolites, and lead to different health effects. Prebiotics with a high degree of polymerisation (resistant starch, inulin) tend to require a much higher dose for efficacy, and prebiotics based upon C6 subunits also tend to require a higher dose for a clinical benefit, because they are more broadly utilised by a range of microbes, both friendly and unfriendly. In contrast, highly selective prebiotics, such as those based upon C5 carbohydrates, have delivered health benefits at doses in the range from 1 – 4 grams per day.

A high dose for efficacy creates challenges for product formulation, and limits the application of prebiotics. Less selective prebiotics that also feed unfriendly microbes have a greater risk of side effects, particularly at higher doses. It is our view that broader utilisation of prebiotics can be achieved if the prebiotic has a higher selectivity for friendly bacteria, which leads to a lower effective dose and more options for product formulation. If your company is considering prebiotics for supplements, food, or beverages, it is important to invest the time to evaluate the key attributes of each prebiotic, and understand their differences, advantages and disadvantages for your specific application.

Brad-Saville-1b

 

Brad Saville is the Chief Science Officer and Founder at Prenexus Health. Brad recently presented at the Probiotics Congress in San Diego.


If you found this interesting, you’ll also like ‘The Future of Prebiotics’.

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