The Future of Prebiotics
Posted 29th November 2017 by Jane Williams
There has been much recent debate over the definition of a prebiotic, culminating in the recent clarification and simplification of wording by ISAPP. Looking forward, what does the future hold for prebiotics?
Where will the next generation of prebiotics come from?
Currently, only the fructans, oligofructose and inulin, and the galacto-oligosaccharides fulfil all of the criteria to be classed as prebiotics. They have been studied extensively for their impact on the gut microbiome and there are human volunteer studies showing real health benefits. However, many other potential prebiotics can be considered.
Plant biomass can provide fermentable oligosaccharides by controlled enzymatic hydrolysis. Such materials are readily available in the form of food processing waste streams. Research is showing promise for xylan and arabinoxylan-derived xylo-oligosaccharides and for oligosaccharides derived from pectins. Plant gums might also be sources of potentially functional oligosaccharides.
The complex exopolysaccharides produced by bacteria have not yet been fully explored as sources of prebiotics. Hydrolysis of these polysaccharides could derive novel carbohydrates with functional benefits.
How do we establish selective utilisation?
A prebiotic should be fermentable and it must also bring about desirable changes in microbial population and metabolic activity because it is a substrate for some organisms in the microbiome and not others. In the early days of prebiotic research, a relatively restricted number of bacterial groups were typically enumerated in studies on fermentation of carbohydrates. This has grown with time as we have developed new DNA-based microbiology techniques better suited to studying the gut microbiome than traditional culture-based methods. We now have the capacity to study the entire ecosystem by DNA sequencing. This gives us a relative ratio of members of the gut microbiome and has the virtue of being untargeted. It does not, however, provide quantitative microbial population data and there are questions about how representative the sequencing-derived data are.
Traditionally in prebiotic research, the emphasis was on finding substrates that were selective for specific desired microbial targets. An understanding of prebiotic metabolism coupled with enzyme biotechnology allows us to consider designing oligosaccharides targeted at specific groups of bacteria to produce optimised prebiotics (termed “optibiotics”). However, in the “everything-has-to-end-in-omics” era we should also be thinking more about profiling and defining the selectivity that exists for the substrates that we have available. Perhaps this shift in emphasis would stimulate innovation and allow more materials to be considered as prebiotic.
Which microorganisms will we target in the future?
Historically, research in prebiotics has tended to focus on selectively stimulating bifidobacteria and lactobacilli. This made sense given the understanding of the functional ecology of the human gut that prevailed in the late 1990s. Bifidobacteria and lactobacilli are, after all, the genera most frequently developed into commercial probiotics and we can ascribe desirable physiological functions to them such as production of antimicrobial compounds and interaction with the immune system.
With increasing research into the gut microbiome, however, we are recognising that other organisms may be considered as health-positive members of the ecosystem. Faecalibacterium prausnitzii and Akkermansia muciniphila are attracting interest for their putative anti-inflammatory properties, for example.
Is it all just Short Chain Fatty Acids?
Recently we have come to recognise the existence of cellular receptors for short chain fatty acids (SCFA) such as acetic, butyric and propionic acids, all products of saccharolytic fermentation in the gut, on many physiological systems around the body. It is clear that SCFA have the potential to regulate the immune system, regulate gut hormone expression, impact on gut barrier function and even to enter the brain and potentially affect mood and cognition. The extent to which SCFA produced in the human gut actually impact on these systems in free-living healthy human beings is not clear at present. Indeed we have a very poor understanding of the amounts of SCFA and other, potentially harmful, metabolites that are produced in vivo.
Whilst it is becoming clear that the systemic effects of prebiotic consumption may be due to SCFA to a greater or lesser extent, the consequences of changing microbial cell populations in the gut need to be elucidated in more detail. Immune surveillance of the microbial populations together with production of antimicrobial compounds may also contribute to the biological effects of prebiotics.
What health impact will prebiotics have made in 10 years and in 20 years’ time?
Most prebiotic health benefits studied to date focus on the gut. Conditions such as IBS, inflammatory bowel diseases, antibiotic-associated diarrhoea and traveller’s diarrhoea have received attention and data are accumulating. Prebiotics have the potential, however, to influence systems outside the gut. Mineral absorption, for example, is one of the best-established physiological functions of prebiotic consumption. Convincing data show that prebiotics can increase calcium scavenging from the large gut and result in increases in bone mineral calcium and bone mineral density. However, long term studies showing that prebiotic consumption in early years actually result in less osteoporosis in later life have not yet been performed.
The ability of prebiotics to have a systemic effect via SCFA and possibly other, as yet unidentified metabolites, means that we can consider using them to address the severe lifestyle disorders that are currently threatening our health and well-being. Recent data show that prebiotics can reduce systemic inflammation and have an impact on blood glucose responses, suggesting their utility in managing Type-II Diabetes. In addition, recent studies have shown an impact on satiety suggesting prebiotics may have a role in weight management.
A very exciting area that holds a lot of promise for the future is the potential of influencing brain function through prebiotic consumption. Prebiotics (together with their probiotic counterparts) that have an impact on the brain have been termed “psychobiotics”; early research suggests they may have an impact on stress, anxiety and, maybe, even sleep patterns. Such research is currently in its infancy but, if it realises its potential, could make a significant impact on people’s lives.
Despite the difficulty in obtaining health claims, the future looks bright for prebiotics.
Bob Rastall is a Professor of Food Biotechnology at the University of Reading. Bob recently presented at the Probiotics Congress in San Diego. The agenda for the meeting in Rotterdam has just launched.
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