How fructan hydrolases break down fructan, a FODMAP group, to aid digestion

Fructan (the ‘O’ in FODMAPs) is a chain of fructose residues joined to a terminal glucose, and is arguably the most common trigger for IBS symptoms. There is a wide array of differently branched and elongated fructans in the plants we eat, so it's no surprise that we consume a different mix of fructan variety. This variety requires a wide spectrum enzyme to break them down. FODZYME’s fructan hydrolase, for instance, has a demonstrated wide fructan substrate specificity, which can target a larger variety of fructan linkages in our daily diets, compared to inulinases, which preferentially act on inulin. 

Can all carbohydrates be digested?

Naturally occurring digestive enzymes are proteins that our body makes to break down food and aid digestion. By virtue of these enzymes, most of the food we eat gets broken down into simpler molecules and absorbed in the small intestine.

Certain carbohydrates in our daily diets, however, do not get digested in the small intestine and pass into the large intestine, and get fermented by our resident gut bacteria. These short, rapidly fermentable carbohydrates are commonly referred to as FODMAPs (Fermentable oligo-, di-, mono-saccharides, and polyols). Bacterial fermentation of FODMAPs produces gas, while the gas coupled with the ability of FODMAPs to pull water into the large intestine can lead to bloating, flatulence, cramping, diarrhea, and constipation.

Although some of these effects are experienced by healthy individuals as well, they can be more pronounced and especially troublesome in individuals suffering from functional gastrointestinal disorders such as Irritable Bowel Syndrome (IBS). Although numerous studies show that a low FODMAP diet (specifically identifying and eliminating individual troublesome carbohydrate sources from meals), can be an effective way of controlling the development of IBS symptoms, routine application of this diet can often be complex and restrictive.

What is fructan?

Fructans (the ‘O’ in FODMAP) are being increasingly recognized as the most common trigger for IBS symptoms. They are long chains (polymers) of fructose (monomer), typically with a sucrose (fructose + glucose) molecule at one end, and are found in foods like garlic, onion, bananas, wheat, and asparagus. Apart from their role as storage compounds that can be mobilized as an energy source for plant growth, they play an important part in protecting plants from stressful conditions such as drought or low temperatures. Plants possess a wide variety of fructan-synthesizing (biosynthetic) enzymes that can produce these fructose polymers using sucrose as a precursor. Thus, a great diversity of fructans that differ from each other by the length of the fructose chains they possess, and the manner in which the fructose-fructose and fructose-sucrose units associate with each other (branching pattern) is generated and stored in various plant parts.

Other factors, such as the developmental stage of the harvested plant part, nutritional status, and exposure to stress can also contribute to differences in fructan content, abundance, and diversity. We typically eat complex meals where we combine various foods. So, as we consume these different plant parts, harvested at different times, following exposure to various storage conditions, our gut must be getting exposed to a wide array and varying quantities of fermentable fructan molecules.

Different categories of fructan

Experts define the following main categories of fructans based on types of fructosyl-fructose linkages: inulin, levan, graminan, agavin, and the neo-type fructans (inulin neoseries and levan neoseries).

Inulin-type and levan-type fructans have a linear structure and contain only β(2-1) and β(2-6) fructosyl-fructose linkages, respectively (Fig 1).

Graminans, on the other hand, are branched and have both β(2-1) and β(2-6) fructosyl linkages in the same molecule.

Neo-type fructans differ from the other fructan classes in that they contain an internal glucose unit instead of a terminal glucose. They are subdivided into the neo-inulin and neo-levan-type fructans. Whereas β(2-1) fructosyl-fructose linkages predominate in the first, β(2-6) fructosyl linkages predominate in the latter.

Agavins are the most complex plant fructans described to date, comprising neoseries type fructans elongated at all three possible branching links from the central glucose.

Upon closely examining Fig 1, we see that the core, linear β(2-1) and β(2-6) fructosyl-fructose linkages abundantly contribute to formation of differently branched elongated fructan chains.

Inulin is the most widely studied fructan as it is the second most abundant plant polysaccharide found in nature and is dominant in plants such as chicory and Jerusalem artichoke.

Graminans are widely reported in cereals such as wheat and barley, and levans are thought to be present only in grasses. However, a closer look at recent work done to identify and quantify the fructans present in common foods reveals that there might be a much greater fructan variety in everyday foods than we realize.

What foods contain fructan?

Wheat is by far the most abundant fructan source in the western diet (70% of the fructans in the American diet) and regarded as one of the most relevant IBS triggers, is mainly believed to contain graminan. However, recent studies show that it might also have neo-type fructans. Onions, another important dietary fructan source, might contain not only inulin as commonly agreed, but also graminans and inulin neoseries fructans. Although the body of research that helps us better understand fructan content and variety in different foods is slowly growing, we are far from comprehensively defining the array of fructans that we might be consuming as part of a complex meal that includes grains, pulses, and vegetables.

Enzymes applied to meals can specifically degrade particular FODMAPs in regular foods and reduce the fermentable carbohydrate burden reaching the colon represent a feasible and easy-to-follow alternative to fixing a complete meal that adheres to the low FODMAP diet requirements.

How fructan hydrolases break down fructan

Just as there is fructan biosynthetic enzyme variety in nature, there are several different naturally occurring enzymes that can degrade or hydrolyze these fructose polymers. Fructan degrading enzymes or fructan hydrolases belong to a certain enzyme family called glycoside hydrolases GH32. One of the earliest described activities of this enzyme class is the invertases that hydrolyze sucrose to its constituent monomers - fructose and glucose.

 What are the different types of fructans?

Fructan hydrolases may either be specific for inulin-like linkages, for levan-like linkages, or may non-specifically hydrolyze both types of fructan links (Table 1). Fructan-degrading enzymes that act specifically on inulin-like linkages are called inulinases.

On the basis of their action on inulin, inulinases are categorized as exoinulinases and endoinulinases. Exoinulinases act on the terminal fructose unit of inulin and produce fructose, and endoinulinases act randomly on the internal glycosidic linkages of inulin and produce fructooligosaccharides (FOS). Fructan degrading enzymes that act specifically on levan-like linkages are called levanases and can also be classified as exo- (terminal fructose residue) and endo - (internal glycosidic bond) levanases based on their site of action in the levan molecule.

How can enzymes supplements help FODMAP digestion?

Given the wide variety of fructans encountered in our diet, enzyme supplements containing fructan hydrolases, like the one in FODZYME®, that exhibit broad target specificity, and target both the inulin-like and the levan-like fructan links would be more effective at reducing the burden of oligomeric fermentable carbohydrates that reaches the intestine compared to ones that only specifically target either the inulin-like or the levan-like fructans.

FODZYME®’s fructan hydrolase with a demonstrated wide substrate specificity can address a larger variety of fructan linkages present in our daily diets. The use of this broad-spectrum fructan hydrolase can reduce the fructan content of meals containing both inulin and levan-like fructans and effectively degrade the linear β-2,1 and β-2,6 fructosyl-fructose links that are abundant in almost all fructan classes described earlier.

Supplementing your meals with FODZYME® could support the consumption of a greater variety of foods that carry significant nutritional and health benefits while reducing the possibility of precipitation of the symptoms of IBS.

Consumption of more diverse, healthy, and delicious foods facilitated by FODZYME®’s broad-spectrum fructan hydrolase application thus represents a non-restrictive and easily applicable alternative to the low-FODMAP diet towards the management of IBS.

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