In the past decades a tremendous interest has grown in the importance of one’s intestinal microbiota, i.e. the microbial community present in our gastrointestinal tract, in relation to health and well-being. Furthermore, methods to measure the microbiome have been increasingly developed and improved. These developments helped researchers to explore the microbiome better and study more and more members of the human gut microbiota and their functions. In this respect prebiotics play a crucial role in maintaining intestinal health as they serve as nourishment for beneficial gut bacteria, fostering a harmonious environment within our digestive system. Prebiotics are defined by ISAPP (International Scientific Association for Probiotics and Prebiotics) as ‘a substrate that is selectively utilized by host microorganisms conferring a health benefit’ (1). Selectivity means that the range of microorganisms affected must be limited, this could be one or several microbial groups, but not all. In addition, a prebiotic must show a health benefit that is scientifically proven and supported by well-controlled research trials. ISAPP recognizes inulin, fructo-oligosaccharides (FOS), and galacto-oligosaccharides (GOS) as prebiotics (1). Inulin and FOS are linked with β-(2-1) bonds, this is a specific bond that is not digested nor absorbed in the human digestive tract. Therefore, upon consumption, they reach the colon intact where bifidobacteria ferment them as energy source while increasing in number. This is called the bifidogenic effect. Bifidobacteria have been maintained exclusively within our ancestors for hundreds of thousands of generations (2). Bifidobacteria are carbohydrate-fermenting (saccharolytic) bacteria associated with beneficial effects such as maintenance of the gut barrier function, inhibiting pathogens and supporting immunity amongst many others (3). This bifidogenic effect of inulin and FOS is confirmed in all age groups, including adults and elderly (4, 5). Doses as low as 3 to 5 g of chicory inulin-type fructans per day can give a bifidogenic effect in adults as show by modern molecular technologies such as 16S rRNA sequencing or quantitative PCR (6). A claim for this effect and even for a prebiotic effect may be made on foods in many countries with conditions depending on the regulatory body. In very young children (6-24 months) a bifidogenic effect was already shown at 2 g/d (7).

The number of human clinical studies investigating the potential for prebiotics in health, especially in the gut-brain axis for potential prevention or treatments for mental health and cognition has dramatically increased in the last years. Researchers are fascinated in the cross-talk between the gut and the brain, the so-called ‘gut-brain axis’, an intricate communication network connecting our gastrointestinal tract to our central nervous system. It was already known that the brain and the gut communicate with each other about swallowing, digestion, and satiety, but also stress and mood seem to be connected to the gut via the gut-brain axis. The microbiota in the colon ferment prebiotic fibers or complex carbohydrates to short chain fatty acids, like butyrate, acetate, and propionate, which support our health (8). The idea that the gut microbiota is associated with and may influence mood disorders started when researchers observed a high prevalence of anxiety and depression disorders in people with gut disorders who often have a disbalanced microbiome. One way of restoring or retaining a healthy microbiome is via diet. Research has shown that prebiotic supplementation may reduce stress responsiveness, anxiety, and depressive-like behavior (9). For example, a few studies have been conducted using inulin and/or oligofructose and showed an improved Mental Health score, mood and episodic memory after ingestion (10, 11). While clearly more human studies are necessary to further explore these associations, the role of prebiotics to positively impact the human gut microbiome has been thoroughly established.

Due to the link of the gut microbiome with health effects, the prebiotic claim is becoming increasingly recognized by consumers. Chicory inulin adheres to the criteria of ISAPP and is currently the only plant-based prebiotic endorsed by ISAPP (1). As described above it has a selective effect on the human gut microbiota of infants to adults to elderly especially increasing the abundance of bifidobacteria as demonstrated by systematic reviews and meta-analyses of numerous human clinical studies (4, 12, 13). A few other genera such as Lactobacillus, Anaerostipes, or Faecalibacterium are also occasionally observed to be increased in abundance and are associated with the metabolic conversion of lactate and acetate produced by bifidobacteria to butyrate (14, 15, 16). These short chain fatty acids are implicated in the many health benefits of inulin (17).

In some countries, health claims may be made on the property of inulin to increase bifidobacteria in the intestine. For example, the functional claim “Prebiotic promotes the growth of good Bifidus bacteria to help maintain a healthy digestive system” can be made in Singapore, provided that the exact identity of the prebiotic is declared on the product label and the food manufacturer/importer can ensure that the amount of prebiotic present in the product can confer the claimed effect. In Thailand there is an approved proprietary health claim statement for inulin, oligofructose and short-chain inulin from chicory roots “inulin/ fructo-oligosaccharide / oligofructose helps to increase bifidobacteria in the intestine” which require specific serving sizes (18). The claim has certain conditions of use, including particular product types, and the food manufacturer must submit the product information to the Thai FDA to confirm all is in accordance with these conditions.

Most importantly, besides the groundbreaking novel research on prebiotics impact on mental health and cognition, inulin has well-established scientifically proven beneficial health effects such as improving digestive health based on numerous human clinical studies (19, 20, 21, 22). In the EU, there is an authorized health claim for chicory inulin for improved stool frequency (23). Thus, numerous randomized controlled clinical trials support both the selective gut microbiota effect and health benefit of inulin.

As inulin conforms to all the ISAPP prebiotic definition criteria, the term prebiotic may be used in different countries on food labels provided various country regulation-specific conditions are met. In the United States, for example, ‘prebiotic’ may be made on product labels by food manufacturers. This is considered a structure-function claim which is allowed provided there is sufficient substantiation in the form of a dossier developed by the manufacturer making the claim.

Health claims on foods in the European Union are regulated by the EU Regulation on Nutrition and Health Claims Made on Food (24). Based on the advice of the European Food Safety Authority (EFSA), the European Commission states that the claim “contains prebiotic” is considered an implied general health claim. These general health claims or Article 10(3) messages can be used if they are accompanied by a specific health claim authorized under Articles 13 or 14. EFSA described a prebiotic effect as “referring to aspects related to increasing numbers of bacteria that are considered to be beneficial” (25). As mentioned above, there is an authorized health claim for chicory inulin for improved stool frequency (23). In the scientific opinion EFSA acknowledged that native chicory inulin could exert an effect on stool frequency by stimulating bacterial growth in the gut and by increasing bacterial cell mass, thus linking inulin, the gut microbiota, and the bowel habit benefit. Consequently, a message such as ‘inulin is a prebiotic’ may be made in conjunction with the authorized inulin bowel habit health claim provided all other conditions of use are met.

Currently certain European countries have initiatives to use the term prebiotic for example in Italy for certain prebiotics such as inulin and FOS (26).

The strong and solid scientific evidence for chicory inulin in terms of impact on the microbiota and substantiated health benefits is essential supporting such regulatory initiatives.

Perspectives
Inulin is a clinically proven prebiotic with substantial scientific data based on more than 20 years of research especially gently maintaining bowel regularity due to balancing the composition of the gut microbiome. This strong science has consequently generated a variety of health claims globally for bifidogenic or improved microbiota, to improved digestive health and prebiotic, depending on the country/region. In the EU, inulin has an authorized health claim for maintaining bowel habit, besides blood glucose lowering. Remarkably a recent study showed intake of prebiotic inulin in healthy elderly twins supported improved cognition (27). Such emerging science in the field of prebiotic and cognition considering current aging populations is an exciting development.